Anil Mahajan

FORMULATION AND EVALUATION OF FAST DISSOLVING

TABLETS OF KETOPROFEN
Submitted by
MAHAJAN ANIL ARUN
Reg. No: 09PU178
Dissertation submitted to
Rajiv Gandhi University of Health Sciences,
Karnataka, Bangalore.
In partial fulfillment of
the requirements for the award of the degree of
MASTER OF PHARMACY
IN
PHARMACEUTICS
Under the guidance of
Mr. R. RAMESH
M.Pharm.
Professor & Head of the Department
DEPARTMENT OF PHARMACEUTICS
Dr.H.L.T.COLLEGE OF PHARMACY
KENGAL, CHANNAPATANA.
2011
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation entitled “FORMULATION AND
EVALUATION OF FAST DISSOLVING TABLETS OF KETOPROFEN” is a
bonafide and genuine research work carried out by me under the guidance of
Mr. R. RAMESH, Professor.
Date: Signature of the candidate
Place: Channapatna MAHAJAN ANIL ARUN
ii

Dr. H.L.T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA - 571502
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation entitled “FORMULATION AND
bonafide research work done by MAHAJAN ANIL ARUN in partial fulfillment
of the requirement for the degree of Master of Pharmacy in Pharmaceutics.
Date: Mr. R. RAMESH

M. Pharm.
Place: Channapatana Department of Pharmaceutics
Dr. H.L.T. College of pharmacy
Kengal, Channapatana.
iii

Dr. H.L.T. COLLEGE OF PHARMACY
KENGAL, CHANNAPATNA - 571502
ENDORSEMENT BY THE H.O.D., PRINCIPAL/HEAD OF

THE INSTITUTION
This is to certify that the dissertation entitled “FORMULATION AND

bonafide research work done by MAHAJAN ANIL ARUN under the guidance of
Mr. R. RAMESH, Professor, Department of Pharmaceutics, Dr. H.L.T. College
of Pharmacy, Channapatna.

Mr. R.RAMESH Mr. R.RAMESH

M. Pharm. M. Pharm.
Head of the Department Professor and Principal,
Department of Pharmaceutics Dr. H.L.T College of Pharmacy
Dr. H.L.T College of Pharmacy Kengal, Channapatna
Kengal, Channapatna
Date: Date:
Place : Place:
iv

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
Copyright
Declaration by the Candidate
I hereby declare that the Rajiv Gandhi University of Health Sciences,
Bangalore, Karnataka shall have the rights to preserve, use and disseminate
this dissertation/ thesis in print or electronic format for academic / research
purpose.
Date: Signature of the candidate

Place: Channapatna MAHAJAN ANIL ARUN
© Rajiv Gandhi University of Health Sciences, Karnataka.
v

ACKNOWLEDGEMENT
I offer my adoration to God Almighty who created me, gave me the strength
and courage to complete my dissertation and given me the opportunity to thanks all
those people through whom this Grace was delivered to me.
I take it as a privilege to sincerely express my deep sense of gratitude and

thank my guide, Mr. R. Ramesh, Professor & Principal Department of
Pharmaceutics, Dr. H.L.T. College of Pharmacy, whose meticulous guidance,
valuable suggestions and constant motivation enabled me to complete this
dissertation.
I express my heartfelt thank to Mr. S. Murlidhar, Associate Professor,

Department of Pharmaceutics, Dr. H.L.T. College of Pharmacy, whose inspiring
support, valuable suggestions, scholarly remarks and guidance made me to complete
this project successfully.
It is my pleasure to thank Dr.T.V.Narayana, Chairman of Dr. H.L.T. College

of Pharmacy dynamic approach towards students made us easy feeling during the
course of study.
I take this opportunity to thanks Dr. Ashok Kumar D., Professor, Department
of Pharmacognosy, and Mr. Gurumurthy M., Associate Professor, Mr. Syed Azhar
Nizami, Associate Professor and Mr. Kumara Prasad S. A., Assistant Professor,
Department of Pharmaceutical Chemistry, Dr. H.L.T. College of Pharmacy for their
valuable guidance, suggestions and support during my M.Pharm course.
It’s a great pleasure to utilize this unique opportunity to express my deep

sense of gratitude and offer my most sincere and humble regards to Dr.P.P.Thampi &
Mrs. Sarala Thampi Professors, for their continuous encouragement and support in
completion of my Course and Dissertation successfully.
I would like to express my sincere and heartfelt thanks to Mrs. Benny Beby,
Mrs. Usha balkeshav Lecturers, K.C.P. College of Pharmacy, Bangalore, for their
kind help who were, and still are my guiding light and support during my course of
Pharmacy education and profession.
I would like to take this opportunity to express my heartfelt gratitude and

thank sincerely Mr. Vishwanath Pawar senior scientist, Zydus Cadila, Ahmadabad,
vi

for his valuable suggestions and constant guidance in the formulation aspects, which
gave a proper shape to my research work.
I would like to thanks Mr. Sandip for providing me gift sample of Ketoprofen
and Mr. Ajani for providing me gift samples of excipients.
I am thankful for utilizing the services of Library and Information Centre of

our college. I am thankful to Mrs. Susheela Librarian and Mr. Umesh, Asst.
Librarian for their help in all the work starting from book references to literature
survey.
I am also thankful Mr. Gangadhar, Mr. Srinivas, Mrs. B. Pramila and to

other non-teaching staff for their kind co-operation. Further, I heartily thankful to
Mr. Adinarayan, & Parmesh Lab. Technician, Mr. Shankar and Mr. Prakash for
timely help.
I would like to thank my seniors, my juniors Nawaz, Kranthiteja, Pragnesh,

Kiran and others for their co-operation and help.
My special thanks to my classmates Naresh, Rakesh, Aakif, Sachin, Jaypal,

Balvenkat Reddy Mamata, Vidyasagar, Anil, Geethanjali, Rajarao, and Sarath for
their understanding, cooperation and encouragement in all my endeavors.
I would also like to thank my friends Naresh, Amol, Vinod, Sandeep, Yogesh,
Shaila, Savitri, Dhanajay, Sunil, Imran, Mangesh, Pravin, Jaydeep, Mahesh,
Tushar, Ajay and others who are directly or indirectly involved in motivating,
encouraging and supporting me all through my career.
I am blessed indeed to have such caring and loving parents, my mother

Smt. Kamal Mahajan, my father Sri. Arun Mahajan, my grandmother
Smt. Tulasabai Mahajan and elders throughout my get-up-and-go and it is those to
whom I like to dedicate this thesis.
Words will fall short to express my feelings for my father who is a very simple,
down to earth and a faultless person. He taught me the biggest lesson of life that is
hard work, honesty and self confidence. He has been the first person to tell me all I
needed to know about the value of higher education in becoming a better person by
his simple eloquence. Education commences at the mother’s knee, my Mamma is the
soul of my energy. Her blessings have always led me to tag along the right path. I
vii

cannot repay her silent patience and constant encouragement. She stood by me
whenever I felt let down, pepped me up when my spirit dampened.
With all my love and affection, I am indebted to my parents, and all my family
members, my sisters Mrs. Pratibha, Mrs. Manisha and my jiju Mr. Ravindra Patil,
Mr. Dipak Choudhari and my uncle Mr.Gajanan Sonawane for their constant
encouragement during my entire career.
I also express my hearty thanks to Central Bank of India, Erondol branch for
providing me education loan for my study.
I again thank all those who were involved in my accomplishments directly or

indirectly.
Date:
Place: (MAHAJAN ANIL ARUN)
viii

ABBREVIATIONS USED
Abbreviation Full Form
CA : Citric Acid
cm : Centimeter (Unit of length)
ρ : Density
0
C : Degree Centigrade (Unit of Temperature)
DSC : Differential Scanning Calorimetry
e.g. : For example
FDT : Fast Dissolving Tablets
FT-IR : Fourier Transform Infrared
g : Gram (Unit of weight)
h : Hour (Unit of time)
IP : Indian Pharmacopoeia
IR : Infrared
kg : Kilogram (Unit of weight)
et al. : Latin et alii (and others)
M : Mass
µg : Microgram
mg : Milligram (Unit of weight)
min : Minute (Unit of time)
ml : Milliliter (Unit of volume)
PM : Physical Mixture
% : Percentage
Sec : Second (Unit of time)
SBC : Sodium Bicarbonate
SD : Solid Dispersion
SEM : Scanning Electron Microscopy
SSG : Sodium Starch Glycolate
USP : United States Pharmacopoeia
UV : Ultraviolet
V : Volume
w/v : Weight by Volume
w/w : Weight by Weight
XRD : X-Ray Diffraction
ix
ABSTRACT:
Ketoprofen is non-steroidal anti-inflammatory drug; mainly used for osteoarthritis
and rheumatoid arthritis. The major problem with this drug is its very low solubility in
biological fluids; which results in poor solubility after oral administration. Therefore solid
dispersion of Ketoprofen with PEG-6000 and PVP K30 in different weight ratios (1:1, 1:2,
1:3) were prepared with a view to increase its water solubility. The solid dispersions were
evaluated by solubility study, drug content, in-vitro drug release study, dissolution efficiency
and characterized by FT-IR, DSC, XRD and surface morphology by SEM. The Ketoprofen
SD with PVP K30 (1:3) ratio showed maximum amount of drug release hence it selected for
Fast Dissolving Tablets formulation. The Fast Dissolving Tablets of Ketoprofen was prepared
by direct compression technique by addition of superdisintigrant like Sodium starch glycolate,
Crosscarmalose sodium, and Crospovidone in different concentration (1-5% w/w) and by
effervescence technology by using combination of (2:3 ratio) Citric acid and sodium
bicarbonate in different concentration (1-5% w/w) with a view to enhance the patient
compliance. Directly compressible dextrose was used to enhance the mouth feel. The
prepared batches of tablets was evaluated for hardness, friability, disintegration time, wetting
time, dispersion time, drug content uniformity and in-vitro drug release in 6.8 pH Sorenson’s
buffer measured at 260 nm. Among all formulations, F15 containing 5% w/w of
Crospovidone is best having least disintegration time 25.68 seconds and release 99.55% of
drug in 20 minutes. The formulation F4, F10, F18 and best formulation F15 was selected for
accelerated stability study at 400 C (75% RH) for period of 3 months. Stability study confirms
there is no significantly change in hardness, friability, disintegration time, drug content and
in-vitro drug release pattern.
Keywords: Ketoprofen, Solid dispersion, Direct compression, Fast dissolving Tablets,
Superdisintigrants, Effervescent method, Stability Study.
x

CONTENTS
S. NO. PARTICULARS PAGE NO.
1 INTRODUCTION 1-44
2 AIM AND OBJECTIVES 45-47
3 REVIEW OF LITERATURE 48-100
4 METHODOLOGY 101-122
5 RESULTS 123-165
6 DISCUSSION 166-176
7 CONCLUSIONS 177-179
8 SUMMARY 180-181
9 REFERENCES 182-194
10 ANNEXURES 195-196
xi
LIST OF FIGURES
Figure No. Title Page No.

A schematic representation of the bioavailability
1 enhancement of a poorly water-soluble drug by solid 4
dispersion compared with conventional tablet or capsule
2 Disintegration of tablet by wicking and swelling 31
3 Disintegration by deformation and repulsion 33
Various Technologies Used to Manufacture Fast Dissolving
4 34
Tablet
5 Step Involved In Sublimation Process 37
6 Mechanism of Action of Ketoprofen 69
7 Modified Device Used to Determine Disintegration Time 116
8 In vitro Wetting Property 117
9 In Vitro Disintegration Property 117
10 IR Spectra (A) Ketoprofen IP Spectra 124
11 IR Spectra (B) Sample of Ketoprofen 124
12 Differential Scanning Calorimetry Curve of Ketoprofen 125
13 Scan Graph of Ketoprofen 126
Calibration Curve of Ketoprofen in Sorenson’s Buffer (pH
14 128
6.8)
15 IR Spectra of Croscarmallose sodium 129
16 IR Spectra of mixture of Drug and Croscarmallose sodium 129
17 IR Spectra of Sodium Starch Glycolate 129
18 IR Spectra of mixture of Drug and Sodium Starch Glycolate 130
19 IR Spectra of Crospovidone 130
20 IR Spectra of mixture of Drug and Crospovidone 130
Cumulative Percent Release of Ketoprofen from Physical
21 Mixtures of Ketoprofen-PVP K-30 and Ketoprofen-PEG- 135
6000 Systems
Cumulative Percent Release of Ketoprofen from Solid
22 Dispersions of Ketoprofen-PVP K-30 and Ketoprofen-PEG- 135
6000 Systems
23 FT-IR Spectra of PVP K 30. 136
24 FT-IR Spectra of Ketoprofen and PVP K 30. 137
25 FT-IR Spectra of PEG-6000 137
26 FT-IR Spectra of Ketoprofen and PEG-6000. 138
27 DSC of PEG-6000 139
28 DSC of PVP K-30 139
29 DSC of KPVP-3 140
30 DSC of KPEG-3 140
xiv
31 X-Ray Diffraction Curves of Ketoprofen 141
32 X-Ray Diffraction Curves of PVP K-30 141
33 X-Ray Diffraction Curves of PEG-6000 142
34 X-Ray Diffraction Curves of KPVP3 142
35 X-Ray Diffraction Curves of KPEG3 143
36 Scanning Electron Photomicrograph of Ketoprofen 143
37 Scanning Electron Photomicrograph of PVP K30 144
38 Scanning Electron Photomicrograph of KPVP3 144
Effect of Concentration of Superdisintegrant and
39 148
Effervescent Agent on Disintegration Time
40 148
Effervescent Agent on Dispersion Time
41 148
Effervescent Agent on Wetting Time
Zero Order Dissolution Release Profile of Ketoprofen from
42 152
F1-F5
43 152
F6-F10
44 153
F11-F15
45 153
F15-F20
46 First Order Release Profile of Ketoprofen from F1-F5 156
In-vitro release profile of F4 during Stability studies at
50 163
(40°C/75% RH)
51 164
(40°C/75% RH)
52 164
(40°C/75% RH)
53 165
(40°C/75% RH)
xv
LIST OF TABLES
Table
Title Page No.
No.
1. Materials used as carrier for solid dispersion 11
Various commercially available superdisintegrants along with
2. 39
their properties.
3. Comparison of some patented technologies for FDT. 44
4. Typical Properties of Croscarmellose Sodium 73
5. Typical Properties of Sodium Starch Glycolate 75
6. Typical Properties of Crosspovidone 76
7. List of Materials 101
8. List of Equipment Used 102
9. Composition of Ketoprofen-PVP K-30 Physical Mixture 105
10. Composition of Ketoprofen-PEG-6000 Physical Mixture 105
11. Composition of Ketoprofen-PVP K-30 Solid Dispersions 106
12. Composition of Ketoprofen-PEG-6000 Solid Dispersions 106
Formulation of Fast Dissolving Tablet Using Croscarmllose
13. 109
sodium
Formulation of Fast Dissolving Tablet Using Sodium Starch
14. 110
Glycolate
15. Formulation of Fast Dissolving Tablet Using Crospovidone 110
Formulation of Fast Dissolving Drug Free Tablet Using
16. 111
Effervescent Agents
Compressibility Index as an Indication of Powder Flow
17. 112
Properties
18. Angle of Repose as an Indication of Powder Flow Properties 113
19. Weight Variation Limits for Tablets as per IP 114
20 Storage conditions according to ICH guidelines 121
21 Melting point of Ketoprofen 123
22 Solubility of Ketoprofen in Different Solvents 127
23 Solubility of Ketoprofen in Various Buffer Solutions 127
Calibration curve data of Ketoprofen in Sorenson’s Buffer (pH
24 128
6.8)
25 Interpretation of drug polymer interaction study. 131
Solubility data of Ketoprofen, physical mixture and solid
26 132
dispersion in Sorenson’s buffer ph 6.8 at 25oc and 370c
Percent Drug Content of Ketoprofen-PVP K-30 & Ketoprofen-
27. 133
PEG-6000 Physical Mixtures and Solid Dispersions
Dissolution Release Profile of Ketoprofen from Physical
28 134
Mixture
xii
29 Dissolution release profile of Ketoprofen from solid dispersion 134
30 Dissolution Efficiency of Ketoprofen-PVP K30 &/ Ketoprofen 136

-PEG 6000 Physical Mixtures and Solid Dispersions.
31 Interpretation of drug polymer interaction study 138
32 Characterization of Blends 145
33 Characterization of Fast Dissolving Tablets 146
34 Characterization of Fast Dissolving Tablets 147
35 Drug content in the Fast Dissolving Tablets of Ketoprofen 149
36 150
F1-F5
37 150
F6-F10
38 151
F11-F15
39 151
F15-F20
Fit of various kinetics Models for fast dissolving Tablets of
44 158
Ketoprofen
Effect of Storage Condition (40°C/75%RH) on Weight of the
45 159
Ketoprofen Tablets
Effect of Storage Condition(40°C/75%RH) on Hardness of
46 159
the Ketoprofen Tablets
Effect of Storage Condition(40°C/75%RH) on Friability of
47 160
Effect of Storage Condition(40°C/75%RH) on Disintegration
48 160
Time of the Ketoprofen Tablets
Effect of Storage Condition(40°C/75%RH) on Drug Content
49 161
of the Ketoprofen Tablets
50 161
(40°C/75%RH)
51 162
(40°C/75%RH)
52 162
(40°C/75%RH)
53 163
(40°C/75%RH)
xiii
INTRODUCTION
CHAPTER-1.
INTRODUCTION
Oral route has been one of the most popular routes of drug delivery due to its
ease of administration, patient compliance, least sterility constraints and flexible
design of dosage forms.
For many decades treatment of an acute disease or chronic illness has mostly
accomplished by delivery of drugs to patients using conventional drug delivery
system. Even today these conventional drug delivery systems are the primary
pharmaceutical products commonly seen in the prescription. Conventional oral drug
products are formulated to release the active principle immediately after oral
administration to obtain rapid and complete systemic drug absorption.
Drug absorption is defined as the process of movement of unchanged drug
from the site of administration to systemic circulation1.
Systemic drug absorption from a drug product consists of a succession of rate
process for solid oral, immediate release drug products.
The rate process include
¾ Dissolution of the drug in an aqueous environment.
¾ Absorption across cell membranes into systemic circulation.
For drugs that have very poor aqueous solubility, the rate at which the drug
dissolves (dissolution) is often the slowest step and therefore exhibits a rate limiting
effect on drug bioavailability. In contrast, for a drug that has a high aqueous solubility
DEPT. OF PHARMACEUTICS, Dr. H. L. T. COLLEGE OF PHARMACY. Page 1

INTRODUCTION
the dissolution rate is rapid the rate at which the drug crosses or permeates cell
membrane is the slowest or rate limiting step.2, 3.
Together with the permeability, the solubility behavior of a drug is a key
determinant of its oral bioavailability. They have always been certain drugs for which
solubility has presented a challenge to the development of a suitable formulation for
oral administration. Examples such as griseofulvin, digoxin, phenytoin, sulphathiazole
& chloramphenicol come immediately to mind. With the recent advent of high
through put screening of potential therapeutic agents, the number of poorly soluble
drug candidates has risen sharply and the formulation of poorly soluble compounds
for oral delivery now presents one of the most frequent and greatest challenges to
formulation scientists in the pharmaceutical industry.
Consideration of the modified Noyes – Whitney equation provides some hints
as to how the dissolution rate of even very poorly soluble compounds might be
improved to minimize the limitations to oral availability.
dc AD ( C S − C )
=
dt h
Where dc/dt = rate of dissolution
A = Surface area available for dissolution.
D = Diffusion coefficient of the compound
Cs = Solubility of the compound in the dissolution medium.
C = Concentration of drug in the medium at time t

INTRODUCTION
h = thickness of the diffusion boundary layer adjacent to
surface of the dissolving compound.
The main possibilities for improving dissolution according to this analysis are
to increase the surface area available for dissolution by decreasing the particle size of
the solid compound and/or by optimizing the wetting characteristics of the compound
to decrease the boundary layer thickness, to ensure sink conditions for dissolution
and, last but definitely not least, to improve the apparent solubility of the drug under
physiologically relevant conditions.
1.1. INTRODUCTION TO SOLID DISPERSION TECHNOLOGY:
The enhancement of oral bioavailability of poorly water soluble drugs remains
one of the most challenging aspects of drug development. Although salt formation,
solubilization and particle size reduction have commonly been used to increase
dissolution rate and thereby oral absorption and bioavailability of such drugs, there
are practical limitations of these techniques. The salt formation is not feasible for
neutral compounds and the synthesis of appropriate salt forms of drugs that are
weakly acidic or weakly basic may often not be practical. Even when salts can be
prepared, an increased dissolution rate in the GIT may not be achieved in many cases
because of the reconversion of salts into aggregates of their respective acid or base
forms. The solubilization of drugs in organic solvents or in aqueous media by the use
of surfactants and cosolvents leads to liquid formulations that are usually undesirable
from the viewpoints of patient acceptability and commercialization. Although particle
size reduction is commonly used to increase dissolution rate, there is a practical limit
to how much size reduction can be achieved by such commonly used methods as

INTRODUCTION
controlled crystallization, grinding, etc. The use of very fine powders in a dosage
form may also be problematic because of handling difficulties and poor wettability.
In 1961, Sekiguchi and Obi developed a practical method whereby many of
the limitations with the bioavailability enhancement of poorly water-soluble drugs can
be overcome, which was termed as “Solid Dispersion”.
Figure-1: A schematic representation of the bioavailability enhancement of a
poorly water-soluble drug by solid dispersion compared with conventional tablet
or capsule
The advantage of solid dispersion compared with conventional capsule or
tablet formulations is shown schematically in figure-1. From conventional capsules
and tablets, the dissolution rate is limited by the size of the primary particles formed
after the disintegration of dosage forms. In this case, an average particle size of 5µm
is usually the lower limit, although higher particle sizes are preferred for ease of

INTRODUCTION
handling, formulation and manufacturing. On the other hand, if a solid dispersion or a
solid solution is used, a portion of the drug dissolves immediately to saturate the
gastrointestinal fluid, and the excess drug precipitates out as fine colloidal particle or
oily globules of submicron size. Because of such easily promises in the bioavailability
enhancement of poorly water-soluble drugs, solid dispersion has become one of the
most active areas of research in the pharmaceutical field.
1.2. HISTORICAL BACKGROUND:
The effect of the particle size of the drugs on their dissolution rates and
biological availability was reviewed comprehensively by Fincher. For drugs whose
gastrointestinal absorption is rate limited by dissolution, reduction of the particle size
generally increases the rate of absorption and or total bioavailability. This commonly
occurs for drugs with poor water-solubility. For example, the therapeutic dose of
griseofulvin was reduced to 50% by micronization and it also produced a more
constant and reliable blood level. The commercial dose of spironolactone was also
decreased to half by just a slight reduction of particle size. Such enhancement of drug
absorption could further be increased several fold if a micronized product was used.
In 1961, a unique approach of solid dispersion to reduce the particle size and increase
rates of dissolution and absorption was first demonstrated by Sekiguchi and Obi. They
proposed the formation of a eutectic mixture of a poorly soluble drug such as
sulfathiazole with a physiologically inert, easily soluble carrier such as urea. The
eutectic mixture was prepared by melting the physical mixture of the drug and the
carrier, followed by a rapid solidification process. Upon exposure to aqueous fluids,
the active drug was expected to be released into the fluids as fine, dispersed particles

INTRODUCTION
because of the fine dispersion of the drug in the solid eutectic mixture and the rapid
dissolution of the soluble matrix.
Levy and Kanig subsequently noted the possibility of using a solid solution
approach in which a drug is dispersed molecularly in a soluble carrier. In a series of
reports in 1965-66, Goldberg et al presented a detailed experimental and theoretical
discussion of advantages of solid solution over the eutectic mixture.
In 1965, Tachibana and Nakamaru reported a novel method for preparing
aqueous colloidal dispersions of β-carotene by using water-soluble polymers such as
polyvinyl pyrrolidone. They dissolved the drug and the polymer carrier in a common
solvent and then evaporated the solvent completely. A colloidal dispersion was
obtained when the coprecipitate was exposed to water.
In 1966, Mayersohn and Gibaldi demonstrated that the dissolution rate of
griseofulvin could be markedly enhanced when dispersed in polyvinyl pyrrolidone by
the same solvent method.
Chiou and Riegelman recently advocated the application of glass solution to
increase dissolution rates. They used PEG 6000 as a dispersion carrier. It is believed
that this relatively new field of pharmaceutical technique and principles will play an
important role in increasing dissolution, absorption and therapeutic efficacy of drugs
in future dosage forms. Therefore, a thorough understanding of its fast release
principles, methods of preparation, selection of suitable carriers, determination of
physical properties, limitations and disadvantages will be essential in the practical and
effective application of this approach.
In addition to absorption enhancement, the solid dispersion technique may
have numerous pharmaceutical applications which remain to be further explored. It is
possible that such a technique can be used to obtain a homogeneous distribution of a

INTRODUCTION
small amount of drug at solid state, to stabilize unstable drugs, to dispense liquid or
gaseous compounds, to formulate a fast release priming dose in a sustained release
dosage form, and to formulate sustained release regimens of soluble drugs by using
poorly soluble or insoluble carriers.
1.3. DEFINITION AND TYPES OF SOLID DISPERSIONS: 4
1.3.1. Definition:
Solid dispersion technology is the science of dispersing one or more active
ingredients in an inert matrix in the solid stage in order to achieve increased
dissolution rate, sustained release of drugs, altered solid state properties, enhanced
release of drugs from ointment and suppository bases, and improved solubility and
stability.
Advantages:
¾ Rapid dissolution rate that result in an increase in the rate and extent of the
absorption of the drug and a reduction in pre-systemic metabolism. This latter
advantage may occur due to saturation of the enzyme responsible for
biotransformation of the drug as in the case of 17-β-estradiol or inhibition of the
enzyme by the carrier as in the case of morphine-tristearin dispersion. Both can lead
to lower doses of the drug.
¾ Transformation of the liquid form of the drug into a solid from. For
eg: clofibrate and benzylbenzoate can be incorporated into PEG 6000 to give a solid.
¾ Avoidance of polymorphic changes and there by bioavailability problems as in
the case of Nabilone and PVP dispersion.

INTRODUCTION
¾ Protection of certain drugs by PEGs. Eg: cardiac glycosides against
decomposition by saliva to allow buccal absorption.
Disadvantages:
1. Solid dispersions have stability problems.
2. Changes in crystallinity and a decrease in dissolution rate with aging.
1.3.2. Types of solid dispersions: 5
a) Simple eutectic mixture:
An eutectic mixture of a sparingly water soluble drug and a highly water
soluble carrier may be regarded thermodynamically as an intimately blended physical
mixture of its two crystalline component. The increase in surface area is mainly
responsible for increased rate of dissolution. This led to a conclusion that the increase
in dissolution was mainly due to decreased particle size.
b) Solid solutions:
Solid solutions consist of a solid solute dissolved in a solid solvent. A mixed
crystal is formed because the two components crystallize together in a homogenous
one-phase system. Hence, this system would be expected to yield much higher rates
of dissolution than simple eutectic systems.
c) Glass solution of suspension:
A glass solution is a homogenous system in which a glassy or a vitreous of the
carrier solubilizer drug molecules in its matrix. PVP dissolved in organic solvents
undergoes a transition to a glassy state upon evaporation of the solvent.
d) Compound or complex formation:
This system is characterized by complexation of two components in a binary
system during solid dispersion preparation. The availability of the drug from the

INTRODUCTION
complex is dependent on the solubility dissociation constant and the intrinsic
absorption rate of the complex.
e) Amorphous precipitation:
Amorphous precipitation occurs when drug precipitates as an amorphous form
in the inert carrier. The higher energy state of the drug in this system generally
produces much greater dissolution rates than the corresponding crystalline forms of
the drug.
1.4. MECHANISM OF INCREASED DISSOLUTION RATE: 6
The enhancement in dissolution rate as a result of solid dispersion formulation,
relative to pure drug varies from as high as 400 folds to less than two-fold. Corrigan
reviewed the current understanding of the mechanism of release from solid dispersion.
The increase in dissolution rate for solid dispersion can be attributed to a number of
factors. It is very difficult to show experimentally that any one particular factor is
more important than another. The main reasons postulated for the observed
improvements in dissolution of these systems are as follows:
a) Reduction of particle size:
In case of glass, solid solution and amorphous dispersions, particle size is reduced
to a minimum level. This can result in an enhanced dissolution rate due to an increase
in both the surface area solubilization.
b) Solubilization effect:
The carrier material, as it dissolves may have a solubilization effect on the drug.
This was shown to be the case for acetaminophen and chlorpropamide in urea as well
as for numerous other drugs.

INTRODUCTION
c) Wettability and dispersibility:
The carrier material may also have an enhancing effect on the wettability and
dispersibility of the drug in the dissolution media. This should retard any
agglomeration or aggregation of the particles, which can slow the dissolution process.
d) Metastable Forms:
Formation of metastable dispersions with reduced lattice energy would result in
faster dissolution rates. It was found that the activation energies for dissolution for
furosemide was 17 K Cal per mol, whereas that for 1:2 furosemide: PVP coprecipitate
was only 7.3 K Cal per mol.
1.5. SELECTION OF A CARRIER:
The properties of the carrier have a major influence on the dissolution
characteristics of the dispersed drug. A carrier should meet the following criteria to be
suitable for increasing the dissolution rate of a drug-
1. Be freely water-soluble with intrinsic rapid dissolution properties.
2. Be non-toxic and pharmacologically inert.
3. Be heat stable with a low melting point for the melt method.
4. Be soluble in a variety of solvents and pass through a vitreous state upon solvent
evaporation for the solvent method.
5. Be able to preferably increase the aqueous solubility of the drug and
6. Be chemically compatible with the drug and not form a strongly bonded complex
with the drug.

INTRODUCTION
Table-1: Materials used as carrier for solid dispersion
1 Sugars Dextrose, Sucrose, Galactose, Sorbitol, Maltose,
. Xylitol, Mannitol, Lactose.
2 Acids Citric acid, Succinic acid.
3 Polymeric materials Povidone (PVP), Polyethylene glycol (PEG),
Hydroxypropyl methyl cellulose, Methyl cellulose,
Hydroxy ethyl cellulose, Cyclodextrin, Pectin,
Galactomannan, Hydroxy propyl cellulose.
4 Insoluble or enteric Hydroxy propyl methyl cellulose phthalate, Eudragit
Polymer L100, Eudragit S100, Eudragit RL, Eudragit RS.
5 Surfactants Polyoxyethylene stearate, renex, Poloxamer 188,
Texafor AIP, Deoxycholic acid, Tweens, Spans.
6 Miscellaneous Pentaerythritol, Pentaerythrityl tetraacetate, Urea,
Urethane, Hydroxy alkyl xanthins.
1.6. POLYMERS USED IN SOLID DISPERSIONS: 5
Polymers used in solid dispersions are as follows:
a) Polyethylene glycols (PEG):
The term polyethylene glycol refers to compounds that are obtained by reacting
ethylene glycol with ethylene oxide. PEGs whose molecular weight is above 300000
are commonly termed as polyethylene oxides.
Effect of PEG molecular weight:

INTRODUCTION
The dissolution rate of pure PEG decreases with increasing molecular weight. The
dissolution rate of the drug in solid dispersion can be increased with an increase in
molecular weight of PEG. In these cases, the rate at which the polymer dissolved
dictated the rate at which the drug dissolved. Lower molecular weight PEGs melt at
37ºC in the dissolution medium prior to dissolution, further increasing the rate of
dissolution. In some drug-PEG solid dispersion systems, the rate dissolution decreases
with molecular weight upto a certain composition of the drug above which the trend
becomes irregular.
b) Polyvinyl pyrrolidone (PVP):
PVP has a molecular weight ranging from 10,000 to 700,000. It is soluble in
solvents like water, ethanol, chloroform and isopropyl alcohol. PVP is not suitable for
preparation of solid dispersions prepared by melt method because of it melts at a very
high temperature above 275ºC, where it becomes decomposed.
Effect of PVP molecular weight:
The effect of molecular weight of PVP on the rate of dissolution of a drug is more
consistent than for PEG. An increase in molecular weight of PVP will decrease the
dissolution rate of most drugs. An increase in viscosity of PVP solution due to an
increase in molecular weight decreases diffusion of drug molecules from the surface
of viscous material into the dissolution medium. Lower molecular weight PVP has a
short swelling time prior to dissolution resulting in an increase in dissolution rate of
the polymer and drug.
c) Polymers and surface active agent combinations:
The addition of surfactants to dissolution medium lowers the interfacial tension
between the drug and the dissolution medium and promote the wetting of the drug

INTRODUCTION
thereby they enhance the solubility and dissolution of drugs. Ternary dispersion
systems have higher dissolution rates than binary dispersion systems.
d) Cyclodextrins:
Cyclodextrins are primarily used to enhance solubility, chemical protection, taste
masking and improved handling by the conversion of liquids into solids by
entrapment.
Oral administration of cyclodextrins:
Cyclodextrins play an important role in the bioavailability of poorly water
soluble drugs by increasing the rate and extent of dissolution of drug.
Cyclodextrins also have the advantage of:
9 Increasing the stability of the drug.
9 Release profile during gastrointestinal transit through modification of drug
release site and time profile.
9 Decreasing local tissue irritation.
9 Masking unpleasant taste
e) Phospholipids:
Phospholipids are major structural components of cell membranes.
Phosphotidylcholine was first isolated from egg yolk and brain. Its chemical name is
1,2-diacyl-in-glycero-3-phosphocholine. In phosphatidyl ethanolamine and
phosphatidyl serine, the choline moiety is replaced by ethanolamine and serine
respectively. Other phospholipids that occur in tissues include phosphotidyl
ethanolamide (PE), phosphotidyl serine (PS), and phosphotidyl glycerol (PG).
Naturally occuring lecithins contain both a saturated fatty acid and an unsaturated
fatty acids with some exceptions.

INTRODUCTION
1.7. METHODS OF PREPARING SOLID DISPERSIONS: 4, 5, 7.
The basic methods used to prepare solid dispersions are
1. Melting method or fusion method
2. Solvent evaporation method
3. Kneading method
4. Supercritical Fluid Process
1. Melting method
In this method physical mixture of an active agent and a water soluble carrier is
heated until it is melted. The melt is solidified rapidly in an ice bath under vigorous
stirring, pulverizing and sieving.
Rapid congealing is desirable because it results in supersaturation of the drug as a
result of entrapment of solute molecules in the solvent matrix by instantaneous
solidification. The solidification process can be achieved on stainless steel plates
attached to a cooling system to favour rapid heat loss.
Advantages
9 This method is simple and economical.
Disadvantages
9 This method is not suitable for drugs which are unstable at the fusion
temperature or evaporates at high temperatures.

INTRODUCTION
9 This method may produce tacky and intractable nature of the resulting
solidified melt and irregular crystallization owing to the presence of a
miscibility gap on the phase diagram for a given carrier system.
2. Solvent Evaporation Method
Tachibani and Nakumara were the first to dissolve both the drug and carrier in a
common solvent and then evaporate the solvent under vacuum to produce a solid
solution. This enabled them to produce a solid solution of the highly lipophilic β-
carotene in the highly water soluble carrier PVP.
The evaporation method was then taken up by Mayersohn and Gibaldi. By
dissolving both griseofulvin and PVP in chloroform, and then evaporating the solvent,
they were able to achieve a solid dispersion. The release rate of griseofulvin from the
solid dispersion was 5 to 11 times higher than that of micronized drug depending on
the drug/carrier ratio.
An important requisite for the manufacture of a solid dispersion using the solvent
method is that both the drug and the carrier are sufficiently soluble in the solvent. The
solvent can be removed by any one of a number of methods. Temperatures used for
solvent evaporation usually lie in the range 23-650C. The solvent can also be removed
by freeze drying or by spray drying.
It must be remembered that when an organic solvent is to be removed, small
variations in the conditions used can lead to quite large changes in product
performance. Another point to consider is the importance of thoroughly removing all
of the solvents, since most of the organic solvents used have toxicity issues.

INTRODUCTION
Advantages
9 The thermal decomposition of drugs and carriers avoided which can be
associated with the fusion method.
Disadvantages
9 This method has higher cost of preparation.
9 In this there is a use of large quantities of solvent.
3. Kneading method
In this method both drug and polymer was taken in a glass mortar and triturated
by using a small volume of organic solvent to give a thick paste which was kneaded
up to 30 minutes and then kept for air dry. Then the dried mass was scratched and
pulverized and sifted through mesh # 80.
4. Supercritical Fluid Process:
Supercritical CO2 is a good solvent for water insoluble as well as water soluble
compounds under suitable conditions of temperature and pressure. Therefore,
supercritical CO2 has potential as an alternative for conventional organic solvents
used in solvent based processes for forming solid dispersions due to its favourable
properties of being nontoxic and inexpensive. The process developed by Ferro
Corporation consists of the following steps:
Charging the bioactive material and suitable polymer into the autoclave.
Addition of supercritical CO2 under precise conditions of temperature and
pressure, that causes polymer to swell;
Mechanical stirring in the autoclave; and

INTRODUCTION
Rapid depressurization of the autoclave vessel through a computer controlled
orifice to obtain desire particle size. The temperature conditions used in this process
are fairly mild (35–75°C), which allows handling of heat sensitive biomolecules, such
as enzymes and proteins.
Solid dispersion of cabamazepine-PEG8000 has been obtained by this method.
1.8 EVALUATION OF SOLID DISPERSIONS: 5
Various methods are available which can give information regarding the
physical nature of solid dispersion system. The commonly used methods are the
following-
1. Thermal Methods:
This method is most commonly used to observe the Physico-chemical
interactions of two or more compounds. It utilizes the principle of change of thermal
energy as a function of temperature and can be performed by the following
techniques.
• Cooling Curve Method:
Physical mixtures of components in various properties are heated to a
homogenous melt. During the cooling process temperature of each mixture is plotted
as a function of time. Critical temperatures are noted and plotted against composition
to provide the phase diagram.
The method is time consuming, requires relatively larger amounts of samples
and is not applicable to samples that decompose after melting. More over changes in
slope can be mixed, especially if cooling takes place rapidly.

INTRODUCTION
• Thaw Melt Method:
A solidified sample in a capillary tube is heated gradually and the thaw and
melting points are noted by visual observation. Since the method depends on visual
observation the results are not reproducible.
• Thermo Microscopic Method:
Physical mixtures of drug and carrier placed in a slide covered with a cover
slip and scaled with silicone grease to prevent sublimation. The mixture is heated until
it completely liquefies. After cooling, the mixture is reheated. The hae and melting
points are noted and a phase diagram is constructed.
• Differential Thermal Analysis (DTA), differential scanning calorimetry
(DSC):
It is effective for studying phase equilibrium of pure compounds as well as
their mixtures. This method is limited to compounds with high thermal stability and
low volatility. In addition to thaw and melting points, polymorphic transitions,
evaporation, sublimation, dissolvation and other types of decomposition can also be
detected by thermal analysis. The greatest advantage lies in constructing phase
diagrams of high reproducibility.
2. X-ray diffraction method (XRD):
It is very important and efficient tool in studying physical nature of solid
dispersions. In simple eutectic systems, diffraction peaks of each crystalline
compound can be found in the diffraction spectra. In substitutions solid solutions, the
lattice parameter of the solvent crystal is either increased, remains unchanged or
decreased depending on the relative size of the solute atom or molecule. In continuous
solid solutions, there is a shift from the positions of the peaks in one pure component

INTRODUCTION
to those in other. In interstitial solid solutions the diffraction pattern of solvent
component may or may not change while that of the solute component disappears.
The X-ray diffraction method can be applicable in detecting compound or
complex formation. Since the spectra of lattice parameters of a complex are different
from those of pure compound.
3. Dissolution Rate Determination:
This method can be used to study degree or crystallinity in solid-solid
equilibria. This method involves comparison of in-vitro dissolution rates of solute
component from a constant surface tablet with the physical mixture of same
composition. The technique is simple to perform except that in some binary systems,
the tablet may not be constant due to the leaching of particulars into dissolution
media. It has been shown to be applicable to simulated systems of indomethacin-
PEG-6000 and sulphathiazole-urea.
4. Electro Microscopy:
Often used to get primary information of the systems and to detect amorphous
and crystalline structures.
5. Thermodynamic Methods:
The phase diagrams of eutectic and solid solution systems can be evaluated by
phase thermodynamic parameters. The knowledge of heats of fusion, entropies and
partial pressure at various compositions enables the determination of the solubility
gap below the solid-liquid equilibrium temperature.

INTRODUCTION
1.9. FUTURE PROSPECTS:
Despite many advantages of solid dispersion, issues related to preparation,
reproducibility, formulation, scale up and stability limited its use in commercial
dosage forms for poorly water-soluble drugs. Successful developments of solid
dispersion systems for preclinical, clinical and commercial use have been feasible in
recent years due to the availability of surface-active and self-emulsifying carriers with
relatively low melting points. The preparation of dosage forms involves the dissolving
of drug in melted carriers and the filling of the hot solutions into hard gelatin capsules
because of the simplicity of manufacturing and scale up processes, the physico-
chemical properties and, as a result, the bioavailability of solid dispersions are not
expected to change significantly during the scale up. For this reason, the popularity of
the solid dispersion system to solve difficult bioavailability issues with respect to
poorly water-soluble drugs will grow rapidly. Because the dosage form can be
developed and prepared using small amounts of drug substances in early stages of the
drug development process, the system might have an advantage over such other
commonly used bioavailability enhancement techniques as micronization of drugs and
soft gelatin encapsulation.
One major focus of future research will be the identification of new
surfaceactive and self-emulsifying carriers for solid dispersion. Only a small number
of such carriers are currently available for oral use. Some carriers that are used for
topical application of drug only may be qualified for oral use by conducting
appropriate toxicological testing. One limitation in the development of solid
dispersion systems may the inadequate drug solubility in carrier, so a wider choice of
carriers will increase the success of dosage form development. Research should also
be directed toward identification of vehicles or excipients that would retard or prevent

INTRODUCTION
crystallization of drugs from super-saturated systems. Attention must be given to any
physiological and pharmacological effects of carriers used. Many of the surfaceactive
and self-emulsifying carriers are lipidic in nature, so potential roles of such carriers on
drug absorption, especially on their inhibitory effects on CYP-3 based drug
metabolism and p-glycoprotein-mediated drug efflux will require careful
consideration.
In addition to bioavailability enhancement, much recent research on solid
dispersion systems was directed toward the development of extended-release dosage
forms. Physical and chemical stability of both the drug and the carrier in a solid
dispersion are major developmental issues, an exemplified by the recent withdrawal
of ritonavir capsules from the market, so future research needs to be directed to
address various stability issues. The semisolid and waxy nature of solid dispersions
poses unique stability problems that might not be seen in other types of solid dosage
forms. Predictive methods will be necessary for the investigation of any potential
crystallization of drugs and its impact on dissolution and bioavailability, possible
drug-carrier interactions must also be investigated.

INTRODUCTION
1.10. INTRODUCTION FAST DISSOLVING TABLETS
Recent advances in Novel Drug Delivery System (NDDS) aims to enhance
safety and efficacy of already used drug molecule by formulating a convenient dosage
forms for administration and to achieve better patient compliance. To develop a
chemical entity, a lot of money, hard work and time are required. So focus is rather
being laid on the development of new drug delivery systems for already existing
drugs, with enhanced efficacy and bioavailability, thus reducing the dose and dosing
frequency to minimize the side effects. 8
The oral route of administration is the most preferred route due to its many
advantages like ease of administration, accurate dosage, self-medication, pain
avoidance, versatility and patient compliance. 9 The most popular dosage forms being
tablets and capsules, one important drawback of these dosage forms however is the
difficulty to swallow. 10
It is estimated that 50% of the population is affected by this problem which
results in a high incidence of non-compliance and ineffective therapy. The difficulty
is experienced in particular by pediatric and geriatric patients, but it also applies to
people who are ill in bed and to those active working patients who are busy or
traveling, especially those who have no access to water and also in following
conditions like: Parkinsonism, Motion sickness, Unconsciousness and Mentally
disabled persons. 11
To fulfill these medical needs, the pharmaceutical technologists have
developed a novel type of dosage form for oral administration, the Fast Dissolving
Tablets (FDT), tablets that disintegrate and dissolve rapidly in saliva without water.

INTRODUCTION
1.11. FAST DISSOLVING TABLETS:
The fast dissolving tablets usually dissolve in the oral cavity within 15 seconds
to 3 minutes. In another words a fast-dissolving tablet is tablet that dissolves or
disintegrates in the oral cavity without the need of water or chewing.
Fast dissolving tablets are also called as Orodispersible tablets, Quick
disintegrating tablets, Mouth dissolving tablets, Oral rapid disintegrating tablets,
Rapid dissolving tablets, Porous tablets and Rapimelts. However, of all the above
terms, United States Pharmacopoeia (USP) approved those dosage forms as Orally
Disintegrating Tablets (ODTs). Recently European Pharmacopoeia has used the term
Orodispersible tablet for tablets that disperses readily and within three minutes in
mouth before swallowing.
United States Food and Drug Administration (USFDA) define ODT as “A
solid dosage form containing medicinal substances or an active ingredient which
disintegrates rapidly usually within a matter of seconds when placed upon tongue”.
The disintegration time for fast dissolving tablets generally ranges from several
seconds to about a minute.12
1.12. ADVANTAGES OF FAST DISSOLVING DRUG DELIVERY SYSTEM:

13, 14, 15, 16, 17.
• Ease of administration to pediatric, geriatric patients and psychiatric patients.
• Free of the risk of suffocation due to physical obstruction when swallowed,
thus offering improved safety.
• Convenience of administrate accurate dose as compared to liquids.
• Having good mouths feel property.

INTRODUCTION
• No need of water to swallow the dosage from.
• Rapid dissolution of drug and absorption, which may produce rapid onset of
action from the mouth, pharynx and esophagus.
• Pregastric absorption can result in improved bioavailability, reduced dose and
improved clinical performance by reducing side effects.
• New business opportunities: product differentiation, line extension and life-cycle
management, exclusivity of product promotion and patent-life extension.
1.13. LIMITATIONS OF FAST DISSOLVING TABLETS: 18.
• Drugs with relatively larger doses are difficult to formulate into FDT e.g.
antibiotics like ciprofloxacin with adult dose tablet containing about 500 mg of the
drug.
• Patients who concurrently take anticholinergic medications may not be the
best candidates for FDT. Similarly patients with Sjögren's syndrome or dryness of the
mouth due to decreased saliva production may not be good candidates for these tablet
formulations.
• The tablets usually have insufficient mechanical strength. Hence, careful
handling is required.
• The tablets may leave unplesant taste and/or grittiness in mouth if not
formulated properly.

INTRODUCTION
1.14. CHALLENGES TO DEVELOP FAST DISSOLVING TABLET: 19, 20.
I) Mechanical strength and disintegration time-
ODTs are formulated to obtain disintegration time usually less than a minute.
While doing so, maintaining a good mechanical strength is a prime challenge. Many
ODTs are fragile and there are many chances that such fragile tablet will break during
packing, transport or handling by the patients. Tablets based on technologies like
Zydis need special type of packaging. It is very natural that increasing the mechanical
strength will delay the disintegration time. So a good compromise between these two
parameters is always essential.
II) Taste masking-
Many drugs are bitter in taste. A tablet of bitter drug dissolving/ disintegration
in mouth will seriously affect patient compliance and acceptance for the dosage form.
So effective taste masking of the bitter drugs must be done so that the taste of the drug
is not felt in the oral cavity.
III) Mouth feel-
The ODT should not disintegrate into larger particles in the oral cavity. The
particles generated after disintegration of the ODT should be as small as possible.
ODT should leave minimal or no residue in mouth after oral administration. Morever
addition of flavours and cooling agents like menthol improve the mouth feel.

INTRODUCTION
IV) Sensitivity to environmental conditions-
ODT generally should exhibit low sensitivity to environment conditions such
as humidity and temperature as most of the materials used in an ODT are meant to
dissolve in minimum quantity of water.
V) Amount of drug:
For lyophilized dosage forms, the drug dose must be lower than 400 mg for
insoluble drugs and less than 60 mg for soluble drugs.
VI) Aqueous solubility:
Water-soluble drugs form eutectic mixtures, which result in freezing-point
depression and the formation of a glassy solid that may collapse upon drying because
of loss of supporting structure during the sublimation process.
VII) Size of tablet:
It has been reported that the easiest size of tablet to swallow is 7-8 mm while
the easiest size to handle was larger than 8 mm. Therefore, the tablet size that is both
easy to take and easy to handle is difficult to achieve.
VIII) Cost-
The technology used for an ODT should be acceptable in terms of cost of the
final product. Methods like Zydis and Orasolv that require special technologies and
specific packaging increase the cost to a remarkable extent8.

INTRODUCTION
1.15. SELECTION OF DRUGS: 21
The ideal characteristics of a drug to be selected.
No bitter taste.
Dose lower than 20mg.
Small to moderate molecular weight.
Good stability in water and saliva.
Partially non ionized at the oral cavities pH.
Ability to diffuse and partition into the epithelium of the upper GIT (log p>1,
or preferably>2).
Ability to permeate oral mucosal tissue.
1.16. EXCIPIENTS USED IN FAST DISSOLVING TABLET:
• Super disintegrants:
Crosspovidone, Microcrystalline cellulose, sodium starch glycollate, sodium
carboxy methyl cellulose, pregelatinzed starch, calcium carboxy methyl cellulose, and
modified corn starch. Sodium starch glycollate has good flowability than
crosscarmellose sodium. Cross povidone is fibrous nature and highly compactable.
• Flavours:
Peppermint flavor, cooling flavor, flavor oils and flavoring aromatic oil,
peppermint oil, clove oil, bay oil, anise oil, Cardamom flavor, eucalyptus oil thyme
oil, oil of bitter almonds. Flavoring agents include, vanilla, citus oils, fruit essences
• Sweeteners’:
Aspartame, Sugars derivatives

INTRODUCTION
• Fillers:
Directly compressible spray dried Mannitol, Lactose, Dextrose, Sorbitol, xylitol,
calcium carbonate, magnesium carbonate, calcium phosphate, calcium sulfate,
pregelatinized starch, magnesium trisilicate, aluminium hydroxide.
• Surface active agents:
Sodiumdoecylsulfate, sodiumlaurylsulfate, polyoxyethylene sorbitan fatty acid
esters (Tweens), sorbitan fatty acid esters (Spans), polyoxyethylene stearates.
• Lubricants:
Stearic acid, Magnesium stearate, Zinc stearate, calcium stearate, talc,
polyethylene glycol, liquid paraffin, magnesium lauryl sulfate, colloidal silicon
dioxide.
1.17. SUPERDISINTEGRANTS: 22
Disintegrants are substances routinely included in tablet formulations and in
some hard shell capsule formulations to promote moisture penetration and dispersion
of the matrix of dosage form in dissolution fluids. An oral solid dosage form should
ideally disperse into the primary particles from which it was prepared.
Superdisintegrants are generally used at a low concentration, typically 1-10%
by weight relative to total weight of dosage unit. Generally employed
superdisintegrants are croscarmellose sodium (Ac-Di-Sol), crospovidone (CP),
sodium starch glycolate (SSG) etc. which represent example of cross-linked cellulose,
cross-linked polymer and cross-linked starch respectively.

INTRODUCTION
Selection of appropriate formulation excipients and manufacturing technology is
necessary for obtaining the optimized design features of orally disintegrating dosage
forms. Ideally, superdisintegrants should cause the tablet to disrupt, not only into the
granules from which it was compressed but also into powder particles from which the
granules were prepared
1.18. SELECTION OF SUPERDISINTEGRANTS: 22
Although superdisintegrants primarily affect the rate of disintegration, but
when used at high levels they can also affect mouth feel, tablet hardness and friability.
Hence, various ideal factors to be considered while selecting an appropriate
superdisintegrants for a particular formulation should:
¾ Produce rapid disintegration, when tablet comes in contact with saliva in the
mouth/oral cavity.
¾ Be compactable enough to produce less friable tablets.
¾ Produce good mouth feel to the patients. Thus, small particle size is preferred
to achieve patient compliance.
¾ Have good flow, since it improves the flow characteristics of total blend.
1.19. MECHANISM OF ACTION OF DISINTEGRANT: 22
Various mechanisms proposed in this concern include water wicking,
swelling, deformation recovery, repulsion and heat of wetting. It seems likely that no
single mechanism can explain the complex behavior of the disintegrants. However,
each of these proposed mechanisms provides some understanding of different aspects
of disintegrant action.

INTRODUCTION
I. Water wicking
The ability of disintegrant to draw water into the porous network of tablet is
essential for effective disintegration. On keeping the tablet into suitable aqueous
medium, the medium enters into tablet and replaces the air adsorbed on the particles
which weakens the intermolecular bonds and breaks the tablet into fine particles.
Water uptake by tablet depends upon hydrophilicity of the drug/excipients and on
tableting conditions. Unlike swelling, which is mainly a measure of volume expansion
with accompanying force generation, water wicking is not necessarily accompanied
by a volume increase. The ability of a system to draw water can be summarized by
Washburn’s equation:
L2 = (γ Cosθ/2η) × rt
The Washburn equation is too simplistic to apply to a dynamic tablet-
disintegration process, but it does show that any change in the surface tension (γ),
pore size (r), solid-liquid contact angle (θ) or liquid viscosity (η) could change the
water wicking efficiency. L is the length of water penetration in the capillary and t is
the time. This process is also considered as capillary action method.
II. Swelling
Although water penetration is a necessary first step for disintegration, swelling
is probably the most widely accepted mechanism of action for tablet disintegrants. For
swelling to be effective as a mechanism of disintegration, there must be a
superstructure against which disintegrant swells. Figure 2 represents the disintegration
of tablet by wicking and swelling. Swelling of the disintegrant against the matrix
leads to development of a swelling force. A large internal porosity in the dosage form
in which much of the swelling can be accommodated reduces the effectiveness of the

INTRODUCTION
disintegrant. On the other hand, sufficient swelling force is exerted in the tablet with
low porosity. It is worthwhile to note that if packing fraction is very high, fluid is
unable to penetrate in the tablet and disintegration is again slowed down.
Figure 2: Disintegration of tablet by wicking and swelling
III. Heat of wetting
When disintegrants with exothermic properties get wetted, localized stress is
created due to capillary air expansion, which aids in disintegration of tablet. This
explanation, however, is limited to only a few types of disintegrants and cannot
describe the action of most modern disintegrating agents.
IV. Due to release of gases
Carbon dioxide gets released within tablets on wetting due to interaction
between bicarbonate and carbonate with citric acid or tartaric acid. The tablet
disintegrates due to generation of pressure within the tablet. This effervescent mixture
is used when pharmacist needs to formulate very rapidly dissolving tablets or fast

INTRODUCTION
disintegrating tablet. As these disintegrants are highly sensitive to small changes in
humidity level and temperature, strict control of environment is required during
preparation of the tablets. The effervescent blend is either added immediately prior to
compression or can be added into two separate fractions of formulation.
V. Particle repulsive forces
This is another mechanism of disintegration that attempts to explain the
swelling of tablet made with non-swellable disintegrants. Guyot-Hermann proposed a
particle-particle repulsion theory to explain the observation that particles which do not
swell extensively such as starch, could still disintegrates tablets. According to this
theory, water penetrates into tablet through hydrophilic pores and a continuous starch
network is created that can convey water from one particle to the next, imparting a
significant hydrostatic pressure. The water then penetrates between starch grains
because of its affinity for starch surfaces, thereby breaking hydrogen bonds and other
forces holding the tablet together. The electric repulsive forces between particles are
the mechanism of disintegration and water is required for it.
VI. Deformation recovery
Deformation recovery theory implies that the shape of disintegrant particles is
distorted during compression and the particles return to their precompression shape
upon wetting, thereby causing the tablet to break apart. Such a phenomenon may be
an important aspect of the mechanism of action of disintegrants such as crospovidone
and starch that exhibit little or no swelling. Disintegration of tablet by deformation as
well as repulsion is illustrated in Figure 3.

INTRODUCTION
Figure 3: Disintegration by deformation and repulsion
VII. By enzymatic reaction
Enzymes present in the body also act as disintegrants. These enzymes dearth
the binding action of binder and helps in disintegration. Due to swelling, pressure is
exerted in the outer direction that causes the tablet to burst or the accelerated
absorption of water leads to an enormous increase in the volume of granules to
promote disintegration.

INTRODUCTION
1.20. TECHNOLOGIES USED TO MANUFACTURE FAST DISSOLVING

23-29.
TABLET:
The technologies used to manufacture fast dissolving tablets can be classified as:
TECHNOLOGIES
CONVENTIONAL PATENTED
TECHNOLOGIES TECHNOLOGIES
i. Freeze Drying i. Zydis Technology
ii. Cotton Candy Process ii. Orasolv Technology
iii. Tablet Molding iii. Durasolv Technology

iv. Nanocrystal Technology
iv Sublimation
v. Dispersible Tablet Technology
v. Spray Drying vi. Wowtab Technology
vii. Flashtab Technology
vi. Mass extrusion
viii. Lyoc Technology
vii. Direct Compression
ix. Pharmaburst Technology
x. Frosta Technology
xi. Ziplets/advatab Technology
xii. Oraquick Technology
Figure-4: Various Technologies Used to Manufacture Fast Dissolving Tablet

INTRODUCTION
3.10.1. CONVENTIONAL TECHNIQUES:
Lyophilization or Freeze Drying
Formation of porous product in freeze-drying process is exploited in
formulating Fast dissolving tablets (FDT). Lyophilization is a process, which includes
the removal of solvent from a frozen suspension or solution of drug with structure-
forming additives. Freeze-drying of drug along with additives imparts glossy
amorphous structure resulting in highly porous and light weight product. The resulting
tablet has rapid disintegration and dissolution when placed on the tongue and the
freeze-dried unit dissolves instantly to release the drug. However, the FDTs formed
by lyophilization have low mechanical strength, poor stability at higher temperature,
and humidity. Along with above complications and its expensive equipment for
freeze-drying is observed to be limitation of this technology.
Cotton Candy Process
This process is so named as it utilizes a unique spinning mechanism to
produce floss-like crystalline structure, which mimic cotton candy. Cotton candy
process involves formation of matrix of polysaccharides or saccharides by
simultaneous action of flash melting and spinning. The matrix formed is partially
recrystallized to have improved flow properties and compressibility. This candy floss
matrix is then milled and blended with active ingredients subsequently compressed to
Fast dissolving tablets. This process can accommodate high doses of drug and offers
improved mechanical strength. However, high-process temperature limits the use of
this process.

INTRODUCTION
Molding
Molding process includes moistening, dissolving or dispersing the drug with a
solvent then molding the moist mixture into tablets (compression molding with lower
pressure than conventional tablet compression), evaporating the solvent from drug
solution, or suspension at ambient pressure (no vacuum lyophilization), respectively.
The molded tablets formed by compression molding are air-dried. As the compression
force employed is lower than conventional tablets, the molded tablet results in highly
porous structure, which increases the disintegration and dissolution rate of the
product. However, to further improve dissolution rate of the product powder mixture
should be sieved through very fine screen. As molding process is employed usually
with soluble ingredients (saccharides) which offers improved mouth feel and
disintegration of tablets. However, molded tablets have low mechanical strength,
which results in erosion and breakage during handling.
Sublimation
The presence of a highly porous structure in the tablet matrix is the key factor
for rapid disintegration of Fast dissolving tablets. Even though the conventional
tablets contain highly water-soluble ingredients, they often fail to disintegrate rapidly
because of low porosity. To improve the porosity, volatile substances such as
camphor can be used in tableting process, which sublimated from the formed tablets,
Koizumi et al. developed Fast dissolving tablet (FDT) utilizing camphor; a subliming
material that is removed from compressed tablets prepared using a mixture of
mannitol and camphor. Camphor was sublimated in vacuum at 80° for 30 minutes
after preparation of tablets.

INTRODUCTION
Figure5: Step Involved In Sublimation Process
Spray-Drying
Highly porous, fine powders are obtained by this method. Allen et al. utilized
this process for preparing Fast dissolving tablets. The Fast dissolving tablet
formulations consisted of hydrolyzed/unhydrolyzed gelatin as supporting agents for
matrix, mannitol as bulking agent, and sodium starch glycolate or croscarmellose
sodium as disintegrating agent. Disintegration and dissolution were further improved
by adding effervescent components, i.e. citric acid (an acid) and sodium bicarbonate
(an alkali). The formulation was spray dried to yield a porous powder. The fast
dissolving tablets made from this method disintegrated within a minute.
Mass-Extrusion
This technology involves softening the active blend using the solvent mixture
of water-soluble polyethylene glycol and methanol and subsequent expulsion of
softened mass through the extruder or syringe to get a cylinder of the product into
even segments using heated blade to form tablets.

INTRODUCTION
Direct Compression
Easiest way to manufacture tablets is direct compression. Low manufacturing
cost, conventional equipment’s and limited number of processing steps led this
technique to be a preferable one. However disintegration and dissolution of directly
compressed tablets depend on single or combined effect of disintegrant, water soluble
excipients and effervescing agents.
It is essential to choose a suitable and an optimum concentration of
disintegrant to ensure quick disintegration and dissolution. Superdisintegrants are
newer substances which are more effective at lower concentrations with greater
disintegrating efficiency and mechanical strength. On contact with water the
superdisintegrants swell, hydrate, change volume or form and produce a disruptive
change in the tablet. Effective superdisintegrants provide improved compressibility,
compatibility and have no negative impact on the mechanical strength of formulations
containing high dose drugs. The type of disintegrants and its proportion are of prime
importance. Also factors to be considered are particle size distribution, contact angle,
pore size distribution and water absorption capacity. Studies revealed that the water
insoluble superdisintegrants like sodium starch glycolate and Croscarmellose sodium
show better disintegration property than the slightly water soluble agents like
Crospovidone, since they do not have a tendency to swell. Superdisintegrants that
tend to swell show slight retardation of the disintegration property due to formation of
viscous barrier. There is no particular upper limit regarding the amount of
superdisintegrant as long as the mechanical properties of the tablet are compatible
with its intended use. The superdisintegrant may be used alone or in combination with
other superdisintegrants. Commercially available superdisintegrants which are widely
used are listed in the Table 1.1.

INTRODUCTION
Table 2: Various commercially available superdisintegrants along with their
properties.
Sr. no. Name Type Properties Brand name
1. Crospovidone Polyvinyl- Crossed linked Polyplasdone XL,
pyrrolidone Polyvinlypyrrolidone Rapidly Kollidon CL
disperses and swells in water
2. Croscarmellose Modified Cross linked sodium carboxy Ac-di-sol,
Sodium. cellulose methylcellulose. Excellent Primellose,
swelling and water wicking Solutab.
properties.
3. Sodium starch Modified Sodium salt of carboxy methyl Primogel,
Glycolate Starch ether of starch. High swelling Explotab,
capacity and rapid water Glycolys.
uptake
4. Indion 414 Ion exchange Cross linked polyacrylic with Indion 414.
Resin a -COO- functional group and
K+ ionic form. High water
intake facility.
Other superdisintegrants which are rarely used are Gellan gum, Xanthan gum and
Soya polysaccharide.

INTRODUCTION
3.10.2. PATENTED TECHNOLOGIES:
¾ Zydis Technology
This technology includes physical trapping of the drug in a matrix composed
of a saccharide and a polymer. Polymers generally employed are partially hydrolyzed
gelatin, hydrolyzed dextran, dextrin, alginates, polyvinyl alcohol, polyvinyl
pyrrolidine, acacia and mixture of these. The methodology involves solution or
dispersion of components is prepared and filled in to blister cavities, which are frozen
in a liquid nitrogen environment. The frozen solvent is removed or sublimed to
produce porous wafers. Peelable backing foil is used to pack Zydis units. Zydis
formulation is sensitive to moisture and may degrade at humidity greater than 65%
RH.
¾ Durasolv Technology
The tablets produced by this technology utilize the conventional tableting
equipment. Tablets in this are formulated by using drug, nondirect compression fillers
and lubricants. Nondirect compressible fillers are dextrose, mannitol, sorbitol, lactose
and sucrose, which have advantages of quick dissolution and avoid gritty texture,
which is generally present in direct compressible sugar. The tablets obtained are
strong and can be packed in conventional packing in bottles and blisters. Nondirect
compressible fillers generally used in the range of 60-95%, lubricant in 1-2.5%.
¾ Orasolv Technology
This includes use of effervescent disintegrating agents compressed with low
pressure to produce the Fast dissolving tablets (FDT). The evolution of carbon
dioxide from the tablet produces fizzing sensation, which is a positive organoleptic
property. Concentration of effervescent mixture usually employed is 20-25% of tablet

INTRODUCTION
weight. As tablets are prepared at low compression force, they are soft and fragile in
nature. This initiated to develop Paksolv a special packaging to protect tablets from
breaking during storage and transport. Paksolv is a dome-shaped blister package,
which prevents vertical movement of tablet with in the depression. Paksolv offers
moisture, light and child resistance packing.
¾ Nanocrystal Technology
Nanocrystal technology includes lyophilization of colloidal dispersions of
drug substance and water-soluble ingredients filled in to blister pockets. This method
avoids manufacturing process such as granulation, blending, and tableting, which is
more advantageous for highly potent and hazardous drugs. As manufacturing losses
are negligible, this process is useful for small quantities of drug.
¾ Dispersible tablet Technology
It offers development of Fast dissolving tablets with improved dissolution rate
by incorporating 8-10% of organic acids and disintegrating agents. Disintegrating
agents facilitates rapid swelling and good wetting capabilities to the tablets that results
in quick disintegration. Disintegrants include starch, modified starches,
microcrystalline cellulose, alginic acid, cross-linked sodium carboxy methyl cellulose
and cyclodextrins. Combination of disintegrants improved disintegration of tablets
usually less than 1 minute.
¾ Wowtab Technology
“WOW” means without water. This technology utilizes conventional
granulation and tableting methods to produce fast dissolving tablets employing low
and high moldability saccharides. Low moldability saccharides are lactose mannitol,
glucose, sucrose and xylitol. High-moldability saccharides are maltose, maltitol,

INTRODUCTION
sorbitol and oligosaccharides. When these low and high moldable saccharides used
alone tablets obtained do not have desired properties of rapid disintegration and
hardness, so combinations are used. This technology involves granulation of low
moldable saccharides with high moldable saccharides as a binder and compressing
into tablets followed by moisture treatment. Thus tablets obtained showed adequate
hardness and rapid disintegration.
¾ Flashtab Technology
This technology includes granulation of excipients by wet or dry granulation
method and followed by compressing into tablets. Excipients used in this technology
are of two types. Disintegrating agents include reticulated polyvinylpyrrolidine or
carboxy methylcellulose. Swelling agents include carboxymethylcellulose, starch,
modified starch, microcrystalline cellulose, carboxy methylated starch, etc. These
tablets have satisfactory physical resistance. Disintegration time is within 1 minute.
¾ Lyoc Technology
Oil in water emulsion is prepared and placed directly into blister cavities
followed by freeze-drying. Nonhomogeneity during freezedrying is avoided by
incorporating inert filler to increase the viscosity finally the sedimentation. High
proportion of filler reduces porosity of tablets due to which disintegration is lowered.
¾ Frosta Technology
It utilizes the concept of formulating plastic granules and compressing at low
pressure to produce strong tablets with high porosity. Plastic granules composed of:
• Porous and plastic material,
• Water penetration enhancer, and

INTRODUCTION
• Binder.
The process involves usually mixing the porous plastic material with water
penetration enhancer and followed by granulating with binder. The tablets obtained
have excellent hardness and rapid disintegration time ranging from 15 to 30 s
depending on size of tablet.
¾ OraQuick
The OraQuick fast-dissolving/disintegrating tablet formulation utilizes a
patented taste masking technology. KV Pharmaceutical claims its microsphere
technology known as MicroMask, has superior mouth feel over taste-masking
alternatives. The taste masking process does not utilize solvents of any kind and
therefore leads to faster and more efficient production. Also, lower heat of production
than alternative fast-dissolving/disintegrating technologies makes OraQuick
appropriate for heat-sensitive drugs. KV Pharmaceutical also claims that the matrix
that surrounds and protects the drug powder in microencapsulated particles is more
pliable, meaning tablets can be compressed to achieve significant mechanical strength
without disrupting taste-masking. OraQuick claims quick dissolution in a matter of
seconds, with good taste-masking. There are no products using the OraQuick
technology currently on the market, but KV Pharmaceutical has products in
development such as analgesics, scheduled drugs, cough and cold, psychotropics, and
anti-infectives.

INTRODUCTION
Table 3: Comparison of some patented technologies for fast dissolving tablets
Drug release /
Technology Novelty Handling/storage
bioavailability
Zydis First to market. Do not push tablet through Dissolves in 2 to 10
Freeze Dried foil. Do not use dosage form seconds. May allow for
(R.P. Scherer, Inc.)
from damaged package. pre-gastric absorption
Sensitive to degradation at leading to enhanced
humidities >65% bioavailability
Orasolv Unique taste Packaged in patented foil Disintegrates in 5 to 45
masking. Lightly packs seconds depending upon

(Cima Labs, Inc.)
compressed the size of the tablet. No
significant change in drug
bioavailability
Durasolv Similar to Orasolv, Packaged in foil or bottles. If Disintegrates in 5 to 45
but with better packaged in bottles, avoid seconds depending upon

(Cima Labs, Inc.)
mechanical exposure to moisture or the size of the tablet. No
strength humidity significant change in drug
bioavailability
Wowtab Compressed dosage Package in bottles. Avoid Disintegrates in 5 to 45
(Yamanouchi form. Proprietary exposure to moisture or seconds depending upon
Pharma taste masking. humidity the size of the tablet. No
Technologies, Inc.) Smooth melt action significant change in drug
gives superior bioavailability
mouth feel

AIM AND OBJECTIVE
CHAPTER-2.
OBJECTIVES OF THE STUDY
The aim of present research work was to formulate FDT of already used
therapeutic molecule to enhance effectiveness, and to avoid side effects (gastric
irritation) of the drug. For FDT most promising NSAID’s candidate Ketoprofen is
selected for the present study.
Thus the objectives of the work were:
To enhance the solubility and bioavailability of Ketoprofen by Solid
Dispersions technique
Evaluate the potential of Polyvinyl pyrolidone K 30, Polyethylene glycol-6000
as suitable drug carrier systems for delivery of Ketoprofen
Determine the effect of change in polymer and polymer composition and
Drug-polymer ratio on solubility of Ketoprofen.
Study of in-vitro dissolution kinetics of Ketoprofen from the formulated Solid
dispersion systems.
To formulate and evaluate fast dissolving tablets of Ketoprofen, having
adequate mechanical strength, rapid disintegration and fast action.
2.2 RATIONALE BEHIND THE SELECTION OF DRUG:
• Ketoprofen belongs to class II drug under BCS classification i.e. low solubility
and high permeability.
• Ketoprofen is non-steroidal anti-inflammatory drug, which is used in the
treatment of rheumatoid arthritis and osteoarthritis.
DEPT. OF PHARMACEUTICS, Dr.H.L.T.COLLEGE OF PHARMACY. Page 45

AIM AND OBJECTIVE
• One of the major problems with this drug is its low solubility in biological
fluids, which results into poor bioavailability after oral administration.
• The solubility of Ketoprofen in aqueous medium was very low i.e. 0.016
mg/ml in water.
• Absolute bioavailability of the Ketoprofen was 99% and biological half-life is
only 2±0.3 hours that results into poor bioavailability after oral administration.
• Conjugation of Ketoprofen with the different types of carriers to increases the
solubility and dissolution rate of Ketoprofen.
• By increasing the solubility of Ketoprofen, its dissolution rate and
consequently bioavailability is increased.
2.3 PLAN OF WORK:
Based upon the literature survey, the application of solid dispersions results in
increasing the solubility of many poorly soluble drugs, the objective of the present
study, investigated to improve the solubility and consequently bioavailability of
Ketoprofen by using different carriers.
Scheme of proposed work is as follows:
• Analytical method development for analysis using UV Spectrophotometer
method.
o Scanning of λmax of Ketoprofen
o Standard plot of Ketoprofen
• Preparation of Ketoprofen solid dispersions.

AIM AND OBJECTIVE
• Evaluation of Ketoprofen solid dispersions by Solubility, Drug content,
Dissolution efficiency, FT-IR, DSC, XRD, SEM, in-vitro dissolution studies.
• Formulation of Ketoprofen tablets from selected Ketoprofen solid dispersions
• Evaluation of prepared Ketoprofen tablets.
• To evaluate the stability studies of best formulations as per ICH guidelines.

REVIEW OF LITERATURE
CHAPTER-3.
3.1. REVIEW OF LITERATURE
1. Late SG, et.al. (2009), Were investigated effects of calcium silicate
(disintegration-promoting agent) and various lubricants on an optimized
cyclodextrin-based fast-disintegrating tablet formulation. Effects of moisture
treatment were also evaluated at 75, 85 and 95% relative humidities. A two
factor, three levels (32) full factorial design was used to optimize
concentrations of calcium silicate and lubricant. Magnesium stearate, being
commonly used lubricant, was used to optimize lubricant concentration in
optimization study. Results of multiple linear regression analysis revealed that
concentration of calcium silicate had no effect; however concentration of
lubricant was found to be important for tablet disintegration and hardness.30
2. Ahmed I. S, et.al. (2006), Were developed Ketoprofen tablets which dissolve-
rapidly in the mouth. The solubility and dissolution rate of poorly water-
soluble Ketoprofen was improved by preparing a lyophilized tablet (LT) of
Ketoprofen using freeze-drying technique.31
3. Maria Victoria Margarit et.al, (1994), Were prepared SD of Ketoprofen by
using PEG-6000 and compared the dissolution kinetics of the dispersions with
physical mixtures and pure drug. The results of dissolution kinetics studies
showed that PEG-6000, when used as a carrier for solid dispersions, increased
the dissolution rate of Ketoprofen. The t 80% of dissolution for pure drug

(88.85% min) decreased to 1.9, 4 and 22.5 min, respectively, in solid
dispersion containing 10:90, 50:50, and 90:10 proportions of Ketoprofen/PEG-
6000.32
4. Piera Di Martino et.al., (2004), Were studied Ketoprofen-
polyvinylpyrrolidone physical interaction, amorphous solid solutions were
obtained in different proportions by dissolving Ketoprofen and
Polyvinylpyrrolidone K-30 in methanol and by evaporating then under
reduced pressure. The result indicated that in the Ket-PVP co-precipitates, the
ket molecules, interacting with their carboxylic group through hydrogen
bonding with the PVP moieties, are molecularly and irregularly dispersed
within the amorphous solvendum that acts as mechanical substratum for
amorphous stabilization.33
5. R. Jachowicz et.al, (2000), Were prepared ternary solid dispersion of
Ketoprofen with macrogol and kollagen hydrolizate as carriers by different
method (melting, solvent method, different cooling) in different concentrations
of drug/carriers. The best solid dispersion consisted of Ketoprofen-Macrogol
6000-KLHT (1+8.9+0.1) was chosen to formulate the pellets on the basis of
the pharmaceutical availability of Ketoprofen from solid dispersion and the
physical chemical studies. The increase in the amount of released Ketoprofen
from solid dispersion pellets was 3.8 times greater than from the pellets
containing the drug alone.34

6. Vasanthkumar S. et.al., (2008), Were prepared immediate release tablets of
Telmisartan using superdisintegrant like polyplasdone XL-10 at intragranular,
extragranular and partly intra and extragranular level of addition to increase
the rate of drug release from dosage form to increase the dissolution rate and
hence its bioavailability. It was concluded that the immediate release tablets
with proper hardness, disintegration time and with increase rate of dissolution
can be made using polyplasdone XL-10. Formulation F 10 was the best
formulation having disintegration time 4.11 sec.35
7. Melleswara rao et.al, (2008), Were prepared solid dispersion of Meloxicam
by using PVA, PVP, PEG-4000 and PEG-6000 in 1:1, 1:2 and 1:4 ratios by
solvent evaporation method. In-vitro release profile of all SDs (F1 to F12)
were comparatively evaluated and also studied against pure meloxicam. Faster
dissolution was exhibited by SD containing 1:2 ratio of drug: PEG-6000 due
to increase in wettability, hydrophilic nature of the carrier and also due to
reduction in drug crystallinity.36
8. P G Bhole et.al., (2009), Were prepared solid dispersion of Felodipine by
using PEG-6000 and PVA in different ratio by solvent evaporation
method.DSC and XRD analysis demonstrated the conversion of felodipine to
amorphous form with both physical mixture and SD. SD with PVA released
95% of the drug in 85 min as compared with 89%of drug released in 90 min
by SD with PEG-6000. Thus SD with both polymers increased drug release,
particularly grater in case of PVA than PEG-6000.37

9. Dario Leonardi et.al, (2007), Were prepared fast release tablets of Prednisone
by using SD technique. SD was prepared by using PEG-6000 by solvent
evaporation method. As demonstrated by both XRD and SEM, a decreased
crystallinity of both prednisone and the surface morphology of the polymeric
particles explained this improved dissolution rate. The tablets containing those
SD particles had dissolution profiles that were better than those of
conventional tablets without PEG-6000.38
10. M.M. Patel et.al., (2006), Were prepared fast dissolving Valdecoxib tablets
containing SD of Valdecoxib by using mannitol (melt solvent) PEG-6000 and
PVP K-12 solvent evaporation method in different ratio 1:1, 1:2, 1:4, 1:6, 1:8,
1:10. SD with PVP K-12 showed maximum drug release the tablets were
prepared and F1 formulation shows better dissolution than other formulation
and conventional marketed tablets which released only 44.3% drug and
Valdecoxib in β-cyclodextrin , which released 53.4% drug in 20 min, while F1
exhibited almost 100% drug release in 20 min.39
11. D. Nagendrakumar et.al., (2009), Were prepared fast dissolving tablets of
fexofenadine Hcl by effervescent method by using crospovidone,
croscarmalose sodium and sodium starch glycolate along with sodium
bicarbonate and anhydrous citric acid in different ratios. the formulation ECP3
containing 8% w/w of crospovidone and mixture of 24% w/w sodium
bicarbonate, 18% w/w of anhydrous citric acid emerged as the best (t 50% 4
min) based on the in vitro drug release characteristics compared to
conventional commercial tablet formulation (t 50% 15 min).40

12. S.B.Shirsand et.al., (2008), Were prepared fast disintegrating tablets of
Prochlorperazine maleate by effervescence method by using sodium
bicarbonate and anhydrous citric acid in different ratios along with
crospovidone (2-10% w/w), croscarmalose sodium (2-10% w/w), were used as
superdisintegrants. Among the all formulation , the formulation containing
10% w/w of crospovidone and mixture of 20% w/w sodium bicarbonate, 15%
w/w of anhydrous citric acid emerged as the best (t 50% 6 min) based on the in
vitro drug release characteristics compared to conventional commercial tablet
formulation (t 50% 17.4 min).41
13. Bhalerao AV, et.al. (2009), Were developed fast disintegrating tablets of
Clonazepam using superdisintigrants and solid dispersion technique. The drug
is poorly water soluble therefore to enhance the solubility and release of drug,
solid dispersion of drug and PVP K30was prepared by solvent evaporation
method. Different combinations of superdisintegrants such as croscarmellose
sodium, sodium starch glycolate, crospovidone were used. The tablets were
prepared. All the tablets had hardness 3-3.5 Kg/cm2 and friability was less than
1. Among all formulations, formulation F10 prepared by drug:PVPK30 (1:4)
ratio and combination of 5%w/w crosscarmellose sodium and 5% w/w of
sodium starch glycolate showed best dispersion time of 8 sec and faster
dissolution 42
14. Singh J, et.al, (2009), Were formulated and optimized orodispersible
formulation of Meloxicam using a 22 factorial design for enhanced
bioavailiabity. The tablets were made by non-aqueous wet granulation using
crospovidone and mannitol. A22 factorial design was used to investigate the

amount of crospovidone and taste masking, smoothening hydrophilic agent
(manifold), as independent variables, and disintegration time as dependent
response. Formulated orodispersible tablets were evaluated for weight
variation, friability, disintegration time, drug content, wetting time, water
absorption ratio and in vitro drug release.43
15. Radke RS, et.al., (2009), Were formulated orodispersible tablets of Baclofen
using various concentrations of superdisintegrant agents like AC-Di-Sol,
crospovidone, sodium starch glycolate by direct compression method. These
tablets were evaluated for drug content weight variation, friability, hardness,
wetting time and invitro disintegration time. It was concluded that
superdisintergtrants addition technique is a useful method for preparing
orodispersible tablets by direct compression method.44
16. Gangane P.S., et.al, (2009), Were formulated rapid disintegrating tablet of
Gatifloxacin Sesquihydrate using Indion 204, Indion 214, Indion 234, Tulsion
335 (ion exchange resin) as a taste masking agent. The tablet was prepared by
wet granulation technique with three superdisintegrants e.g. sodium starch
glycolate, crosscarmellose sodium and crospovidone. The granules were
examined for angle of repose, bulk density, tapped density and Hauser’s ratio.
The tablets were evaluated for hardness, drug content and friability and
disintegration time. The disintegration in oral cavity was also tested and was
45
found to be 22 sec.
17. Venkatesh D. P., et.al, (2008), Were formulated the taste masked oral –
dispersible tablets of Ambroxol hydrochloride. Cation exchange resins like

Indion-204 and Indion-234 were utilized for the sorption of drug. Drug-
resinates was prepared in drug to ratio of 1:5 and 1:6. Tablets with both the
resins have shown quick disintegrating features, i.e., within 20 sec which is
very characteristics of orodispersible tablets. Almost more than 90% of drug
was released from the both the formulation within 1 hour .46
18. Patel D M, et.al, (2008), Were prepared Etoricoxib fast dissolving tablets.
Granules containing etoricoxib, Menthol, crospovidone aspartame and
mannitol were prepared by wet granulation technique. Menthol was sublimed
from the granules by exposing the granules to vacuum. The porous granules
were then compressed in to tablets. Alternatively, tables were first prepared
and later exposed to vacuum. The tablets were evaluated for percentage
friability and disintegration time. A32 full factorial design was applied to
investigate the combined effect of to formulation variables: amount of menthol
and crospovidone. The results of multiple regression analysis indicated that for
obtaining fast dissolving tablets; optimum amount of menthol and higher
percentage of crospovidone should be used.47
19. Furtado S, et.al, (2008), Were developed orodispersible tablets of Famotidine
containing a subliming agent. Mannitol as a diluent, sodium saccharin as
sweetening agent, alcoholic solution of PVP (10%w/v) as binder and
magnesium stearate with talc as a flow promoter. Addition of camphor in the
formulation improved the tablet properties with respect to wetting time and in
vitro dispersion time. The present study demonstrated potentials for rapid

absorption, improved bioavailability, effective therapy and patient
compliance.48
20. Mizumotu T, et.al, (2008), Were formulated fast disintegrating dosage form
containing taste- masked particles of Famotidine. Partial granulations was
found to be an effective and practical way to address content uniformity,
however, oral disintegration time tended to become longer as content
uniformity improved. The disintegration time was improved considerably by
controlling ambient humidity during the compression process (>50%RH).
Furthermore, since the new fast-disintegrating technology made it possible to
use low compression force, there was no change in the structure or dissolution
rate of the taste-masked particles after compression. Therefore, this system can
produce a taste-masked fast-disintegrating tablet with satisfactory attributes.49
21. Jha SK, et.al, (2008), Were formulated melt-in- mouth tablets of Haloperidol
which is widely used neuroleptic. Though haloperidol is well absorbed after
oral dosing, there is a first pass metabolism leading to a reduced
bioavailability of the drug (60-70%) Therefore, the present investigation is
concerned with the development of melt-in-mouth tablets of haloperidol.
Various formulations were prepared incorporating a combination of
superdisintegrants, croscarmellose sodium, sodium starch glycolate, and
crospovidone by direct compression method. The formulated melt-in-mouth
tables were evaluated for various physicochemical parameters, disintegration
time and in vitro drug release. All the formulations had disintegration time less
than 30s and release maximum amount of drug by 12 min.50

22. Prabhu Namita B., Rao Leena et.al, (2007), Studied the taste masking of
Drotaverine hydrochloride. The drug was treated with cationic exchange
resins, which, by complexation technique masked the bitterness of the drug.
The loading process was optimized for taste masking and drug: resin ratio.
The resinate was evaluated for bulk density, tap density and taste. The
complex was characterized using DSC. The taste masked Drotaverine complex
was incorporated into palatable melt in mouth tablets.51
23. Mukesh C. Gohel, Rajesh K. et.al, (2007), Were prepared and assement of
Novel coprocessed Superdsisintegrant consisting of Crospovidone and Sodium
Starch Glycolate. Corprocessing is defined as combining 2 or more established
excipients by an appropriate process. Coprocessed superdisintegrant consisting
of crospovidone and SSG exhibited good flow and compression
characteristics. Cefixime trihydrate and ibuprofen tablets containing
coprocessed superdisintegrant exhibited quick disintegration and improved
drug dissolution.52
24. Jacob. S, Shirwalkar. A. et.al., (2007) Studied novel co-processed excipients
of Mannitol and Microcrystalline Cellulose for preparing Fast Dissolving
Tablets of Glipizide.Co-processed particles of microcrystalline cellulose and
mannitol were fabricated by spray drying technique to be used as a direct
compression excipient in fast dissolving tablet formulation. Microcrystalline
cellulose passed through sieve no.80, having a volumetric mean diameter (d50)
of 28.35 pm, was used to form composite particles with powdered mannitol
which was previously passed through sieve no. 80, in various mixing ratios

distributed in the microcrystalline matrix in spray dried form compared to
physical mixture of the same combination. The fast disintegration may be due
to the partial amorphization and formation of submicron particles of mannitol.
Fast dissolving tablets of glipizide were prepared by blending with other
excipients and compressed into tablets.53
25. Dina Nath Mishra, Madhu Bindal et.al, (2006) Studied spray dried
excipients based Technique for the Formulation of Orally Disintegrating
Tablets of Valdecoxib (low aqueous solubility) and Metoclopramide (high
aqueous solubility). Spray dried excipient base was prepared using Scientech
spray drier. Super disintegrants (such as Ac-Di-Sol, Kollidon CL, sodium
starch glycolate.) diluent (mannitol) along with sweeting agent (aspartame)
were used in the formulation of tablets. The tablets were evaluated for
hardness, friability, water absorption ratio, disintegration time (DT) and in
vitro drug release.54
26. Jinichi Fukami, Etsuo Yonemochi et.al, (2006) Evaluated of rapidly
disintegrating tablets containing glycine and carboxymethylcellullose. Effect
of glycine as disintegrant on the disintegration behavior of the tablet in the
oral cavity was evaluated. Wetting time prepared from
carboxymethylecellulose (NS-300) having the hardness of 4kg was 3s. Tablet
containing NS-300 showed fastest disintegration compared to other
formulations. Glycine, one of an amino acid, presents excellent wetting nature
and suitable for the fast disintegrating formulation. Ethenzamide and ascorbic
acid were added to the formulation. And their disintegration behaviour was

evaluated. Ethenzamide did not affect the disintegration property; however,
ascorbic acid prolonged disintegration time.55
27. Chaudhari P.D., Kolhe S. R., et.al, (2006) Studied the use of cation
exchange resins to optimize the taste masking of bitter drug Rizatriptan
benzoate. The taste should be masked in order to reduce its bitterness to
increase its palatability and also to improve patient compliance. So attempts
were undertaken to mask the bitter taste by complexation technique using ion
exchange resins. Drug release from the complex is obtained at salivary and
gastric pH.56
28. Gohel. M. C. et.al, (2005) Studied a review of co-processed directly
compressible excipients. The present review out-lines the importance of the
functionality of the directly compressible adjuvants in the formulation of
tablets. The co-processing is the most widely explored method for the
preparation of directly compressible adjuvants because it is cost effective and
can be prepared in-house based on the functionality required. Hence, the
present review focuses on the properties of the co-processed directly
compressible adjuvants available in the market.57
29. Na Zhao and Larry L. Augsburger et.al, (2005) Studied functionality
comparison of 3 classes of superdisintegrants in promoting Aspirin tablet
disintegration and dissolution by Ac-Di-Sol, Primojel, and Polyplasdone
XL10. Ac-Di-Sol was found to disintegrate tablets rapidly into apparently
primary particles; Primojel also apparently disintegrated tables into primary

particles but more slowly; Polyplasdone XL10 disintegrated tablets rapidly but
into larger masses of aggregated particles. The aspirin tablet matrix is
proposed as a model formulation for disintegrate efficiency comparison and
performance consistency testing for quality control purpose.58
30. Abdelbary G., et.al, (2004) Were prepared the orally disintegrating tablets
using a hydrophilic waxy binder (Superpolystate, PEG-6 stearate).
Superpolystate is a waxy material with a melting point of 33-370C and an
HLB value of 9, so it will not only act as a binder and increase the physical
resistance of tables but will also help the disintegration of the tablets as it
melts in the mouth and solubilizes rapidly leaving no residues. The
incorporation of Superpolystate in the formulation of RDT was realized by
means of two different granulation methods: wet granulation by using an
emulsion of this waxy binder as granulating liquid and melt granulation where
the molten form of the binder was used. The potential of the intracranial
addition of croscarmellose sodium as a disintegrating agent was also
evaluated.59
31. Damrongsak Faroongsarng et.al, (2003) Studied the thermal porosity
analysis of croscarmellose sodium and sodium starch glycolate by differential
scanning calorimetry. Croscarmellose sodium (CCS) and sodium starch
glycolate (SSG) were allowed to sorb moisture in 85%, 90%, 95% and 100%
relative humidity (RH) at 400C for 24 hours. The pretreated samples were then
subjected to DSC running temperature ranging from 250C to – 500C at a
cooling rate of 100C/min. The porosity analysis of CCS and SSG was also

done using nitrogen adsorption as a reference method. The nonfreezable
moisture content was refereed to tightly bound, plasticizing water, whereas the
frozen one may be attributed to loosely bound water condensation in pore
structure of CCS and SSG surfaces.60
32. Toshihiro Shimizu et.al, (2003) Studied the formulation of Lansoprazole
Fast-disintegrating Tablet. III. Design of Rapidly Disintegrating tablets. In the
design of the inactive granules, mannitol was used as a basic excipient,
Microcrystalline cellulose, low-substituted hydroxypropyl cellulose (L-HPC),
and crospovidone were used as binders and disintegrants. A new grade of L-
HPC (L-HPC-33) with a hydroxypropoxy group content of 5.0-6.9% was
developed and it has no rough texture due to decrease in water absorption. It
was clarified that L-HPC 33 could be useful as a binder and disintegrant in
rapidly disintegrating tablets. LFDT contain enteric-coated microgranules in
tablet form.61
33. Toshihiro Shimizu et.al, (2003) Studied the formulation of Lansoprazole fast-
disintegrating tablet-I. Effect of Compression on Dissolution Behaviour.
Lansoprazole is an antiulcer agent and is unstable under acidic conditions; we
have developed LFDT as an orally disintegrating tablet containing enteric-
coated microgranules. The effect of compression on dissolution behavior was
investigated, as compression affected cleavage and crushing of the enteric
layer. To decrease cleavage and crushing of the enteric layer, the effects of the
combined ratio of methacrylic acid copolymer dispersion to ethyl acrylate-
methyl methacrylate copolymer dispersion and the concentration of triethly

citrate on the dissolution in the acid stage and the dissolution in the buffer
stage were evaluated.62
34. Yutaka Morita et.al, (2002) Evaluated the disintegration time of rapidly
disintegrating tablets via a novel method Utilizing a CCD Camera. Ordinary
disintegration testing, such as the Japanese Pharmacopoeia (JP) method, faces
limitations with respect to the evaluation of rapid disintegration due to strong
agitation. Therefore, we have developed a novel apparatus and method to
determine the dissolution of the RDT. The novel device consists of a
disintegrating bath and CCD camera interfaced with a personal computer
agitation. Therefore, we have developed a novel apparatus and method to
determine the dissolution of the RDT. The novel device consists of a
disintegrating bath and CCD camera interfaced with a personal computer
equipped with motion capture and image analysis software. Simultaneously,
were also able to detect qualitative information.63
35. Hector Fausett et.al., (2000) Evaluated the quick disintegrating Calcium
carbonate tablets by direct compression and compare it with commercially
available calcium tablets, CC tablets were formulated on a Carver press using
3 different forms of CC direct compressed granules ( Cal-Carb 4450, Cal-Carb
4457, and Cal-Carb 4462 ). The dissolution studies showed that all
formulations released 100% of the elemental calcium in simulated gastric fluid
in less than 20 minutes. In summary, this study clearly demonstrated that
quick disintegrating CC tablets can be formulated without expensive
effervescence technology.64

36. Chaulang G., et.al, (2009), Were prepared solid dispersion of Furosemide in
SSG in ratios of 1:1 and 1:2 by kneading method. The FTIR, DSC, and XRD
showed a change in crystal structure towards an amorphous from of
furosemide. Dissolution data indicated that furosemide dissolution was
enhanced. The sold dispersion formulated in 1:2 ratio showed a 5.40 fold
increase in dissolution and also exhibited superior dissolution characteristics
to commercial furosemide tablets .65
37. Madan J, et.al, (2009), Were prepared fast dissolving tablets of the
nutraceutical, freeze-dried Aloe vera gel by dry granulation method. The
tablets were evaluated for crushing strength, disintegration time, wetting time,
friability, drug content and drug release. A 32 full factorial design was applied
to investigate the combined effect of two formulation variables - amounts of
microcrystalline cellulose and mannitol. The results of multiple regression
analysis revealed that in order to obtain a fast dissolving tablet of the Aloe
vera gel, an optimum concentration of mannitol and a higher content of
microcrystalline cellulose should be used.66
38. Mohapatra A, et.al, (2008), Were prepared the tablets of Metformin using
starch RX1500 and microcrystalline cellulose by direct compression. The
tablets showed erosion behavior rather than disintegration. Then lactose was
incorporated which created pores to cause burst release of drug. But these
tablets did not give good mouth feel. Thus, Pearlitol SD 200 (spray dried
mannitol) was used to prepare tablets by wet granulation (10%
polyvinylpyrrolidone in Isopropyl alcohol as binder). The optimized batches

of tablets (LMCT3 and MP13) not only exhibited desired mouth feel but also
disintegration time, In-vitro dispersion time, water absorption ratio, and In-
vitro drug release. All the batches contained 15% starch 1500 and 4% of
croscarmellose sodium. The optimized batches prepared by direct compression
and wet granulation showed 85% drug release at 4 min and 8 min.67
39. Mohammad BJ, et.al, (2007), Were prepared Carbamazepine solid
dispersions by the cogrinding technique using an insoluble but highly
hydrophilic crospovidone and soluble hydroxypropylmethylcellulose (HPMC)
as the carriers. The ratios of drug to carrier were 1:1, 1:5 and 1:10.
Comparison of the dissolution of the drug from its cogrounds with that of the
unground drug, its ground form and the corresponding physical mixtures
revealed considerable differences. The percentage of drug dissolved during the
first 30 min, (%D30), for the ground and coground drug was 75-95, whereas
the %D30 for unground drug and its physical mixtures ranged from 41-62.68
40. Fars KA, et.al, (2007), Were formulated Metoclopramide FDT with sufficient
mechanical strength and fast disintegration from bases prepared by both spray
and freeze drying techniques. Different disintegration accelerators were
utilized to prepare the proper FDT using various super-disintegrants (Ac-Di-
Sol, Kollidon and sodium starch glycolate), a volatilizing solvent (ethanol) and
an amino acid (glycine).69
41. Malke S, et.al, (2007), Were prepared fast dissolving tablets of
Oxycarbazepine containing Avicel PH 102 as a diluent and Ac-Di-Sol as a

superdisintegrant by wet granulation process. All the formulations were
evaluated for characteristics such as hardness, friability, weight variation,
wetting ability, and disintegration time and dissolution rate. The disintegration
time was found to be 28±5 sec and drug release of not less than 90% within 30
min.70
42. Modi A, et.al, (2006), Were investigated enhancement of the dissolution
profile of Valdecoxib using solid dispersion with polyvinylpyrrolidine. They
also described the preparation of fast-dissolving tablets of Valdecoxib by
using high amount of superdisintegrants. A phase solubility method was used
to evaluate the effect of various water-soluble polymers on aqueous solubility
of valdecoxib. The dissolution of valdecoxib improved significantly in solid
dispersion products ( 85% in 5 min). The tablets containing solid dispersion
exhibited better dissolution profile than commercial tablets.71
43. Shirwaikar AA, et.al, (2004), Were formulated Atenolol as fast disintegrating
tablet using three superdisintegrants, croscarmellose sodium (Ac-Di-Sol),
crospovidone (Polyplasdone XL) and sodium starch glycolate (Explotab). All
the superdisintegrants were used at different concentration levels to assess
their efficiency and critical concentration level.72
44. Ravi Kumar et.al, (2009), Were prepared ODTs of Aceclofenac by wet
granulation technique using camphor as subliming agent and sodium starch
glycolate together with crosscarmellose sodium as superdisintegrants. The
camphor was sublime and forms porous granules. All the formulation showed

low weight variation with dispersion time less than 50 seconds and rapid in-
vitro dissolution (97.4-99.1%). The result revealed that the tablets containing
subliming agent had a good dissolution profile.73
45. D.M.Patel et.al., (2004), Was studies in formulation of ODTs of Rafecoxib by
using three different superdisintegrants croscarmellose sodium, crospovidone
and sodium starch glycolate by wet granulation method, from result it can be
concluded that the tablets containing crospovidone exhibit quick disintegration
time 6 seconds and wetting time 5 seconds.74
46. Manivannan Rangasamy et.al, (2009), Was designed and evaluated the fast
dissolving tablet of Terbutaline sulphate by incorporating superdisintegrats
such as Explotab, Ac-di-sol, and Polyplasdone XL, by direct compression
method. Among all ,the formulation F9 (containing 5 % w/w conc. of
polyplasdone XL) was considered to be the best formulation, which release up
to 99.33% of the drug in 10 min.,and dispersion time 9 seconds.75
47. Sarasija Suresh et.al, (2007), Were prepared mouth dissolving tablet of
Salbutomol sulphate by wet granulation process using sublimable components
camphor and sodium bicarbonate. Evaluation of the tablets showed that all the
tablets were found to be within official limits and disintegration time from 5-
40 seconds. Among all, the formulation containing microcrystalline cellulose
and sodium bicarbonate showed the least disintegration time of 5 seconds.76

48. H.S.Mahajan et.al, (2004), Have worked on the mouth dissolved tablets of
Sumatriptan succinate were prepared using superdisintegrants sodium starch
glycolate, carboxymethylcellulose, sodium and treated agar by direct
compression method. The tablet disintegrates invitro and in vivo within 10 to
16 second and 12 to 18 seconds respectively. Almost 90% of drug was release
from all the formulations within 10 minutes.77
49. Shailesh Sharma et.al, (2009), Were prepared Fast dissolving tablets of
Promethazine Theoclate by direct compression method using Ac-Di-Sol,
sodium starch glycolate and crospovidone as superdisintegrants in different
concentration. The tablet containing Ac-Di-Sol showed superior organoleptic
properties along with excellent in-vitro disintegration time (52 sec.) and drug
release (72.57%) as compare to other formulations.78
50. A. S. Mundada et.al., (2008), Were formulated dispersible taste masked
tablets of Roxithromycin by using weak cation exchange resins Indion 214
and Amberlite IRP64, polymer Carbapol 934P.The loading process was
optimized for the pH of loading solution and resin or polymer : drug ratio. In-
vitro drug release studies showed more than 80% drug release from the
optimized formulation within 30 min. Amberlite IRP64 was found to be better
complexing agent for masking the bitter taste of Roxithromycin.79

3.2. DRUG REVIEW
KETOPROFEN 80-85.
Structure
Chemical Name 2-(3-benzoylphenyl)-propionic acid, 3-Benzoyl-α-
methylbenzene acetic acid
Molecular formula C16H14O3
Molecular weight 254.29
Description White or off white, odorless, tasteless, nonhygroscopic,
fine to granular powder.
Melting point 94-97°
Category Anti-inflammatory; analgesic.
Solubility Freely soluble in ethanol, chloroform, acetone, ether
and soluble in benzene and strong alkali. Practically
insoluble in water at 200 C.
Identification:
The infra-red absorption spectrum is concordant with the reference spectrum
of ketoprofen. The light absorption in the range 230 to 360 nm of a 0.002 % w/v
solution in methanol (75%) exhibits a maximum only at about 258 nm; absorbance at
about 258 nm is about 1.3.

Loss on drying:
When dried to constant weight at 600C at a pressure not exceeding 0.7 kPa,
loses not more than 0.5% of its weight. Use 1 g.
Residue on ignition:
Not more than 0.2%
Sulphated ash:
Not more than 0.1%
Assay:
Weigh accurately about 0.5 gm., dissolve in 25 ml of ethanol (96%)
previously neutralized to phenolphthalein solution, add 25 ml of water and titrate with
0.1M sodium hydroxide using phenolphthalein solution as indicator. Each ml of 0.1M
sodium hydroxide is equivalent to 0.02543 gm. of C16H14O3.
Storage:
Store in well-closed container.
Pharmacological profile:
Ketoprofen is an aryl propionic acid derivatives, it is an NSAID with
pronounced analgesic, anti-inflammatory and anti-pyretic action. It may offer
significant advantages over Aspirin and Indomethacin for many patients, since they
usually are better tolerated. Nevertheless, propionic acid derivatives share all the
detrimental features of the entire class of drugs. The pharmacodynamics properties of
the propionic acid derivatives do not differ significantly. All are effective COX
inhibitors, although there is considerable variation in potency.
Mechanism of action:
Ketoprofen is a non-steroidal anti-inflammatory drug with analgesic and
antipyretic properties. During inflammation, pain and fever, arachidonic acid is

liberated from phospholipid fraction of the cell membrane; arachidonic acid is then
converted via cyclo-oxygenase (COX-1 and 2) pathways to prostaglandins (PGs),
bradykinins, leukotrienes etc, which are the chemical mediators for the above
conditions. Ketoprofen mainly acts by inhibition of both cyclooxygenase-1 and
cyclooxygenase-2 which leads to the inhibition of prostaglandin synthesis and
leukotriene synthesis, to have antibradykinin activity, as well as to have lysosomal
membrane stabilization action. Antipyretic effects may be due to action on the
hypothalamus, resulting in an increased peripheral blood flow, vasodilation and
subsequent heat dissipation.
Figure-6: Mechanism of Action of Ketoprofen
Pharmacokinetic data:-
Oral availability (%): 100%
Metabolism: Hepatic
Excretion (%): Renal 50 - 90%, feces 1 -8 %
Plasma clearance: 1 – 2 ml/min/kg
Volume of distribution (Vd): 0.1 – 0.2 L/kg

Peak time (h): 0.5 – 2 h.
Peak plasma concentration (mcg/ml): 4.1 mcg/ml
Protein binding (%): 99%
Half-life (h): 2.0 ± 0.3 h
Onset: 30 min
Clinical Pharmacology:
Ketoprofen is a nonsteroidal anti-inflammatory drug with analgesic and
antipyretic properties. In anti-inflammatory models Ketoprofen has been shown to
have inhibitory effects on prostaglandin and leukotriene synthesis, to have antibrady-
kinin activity, as well as to have lysosomal membrane-stabilizing action. However, its
mode of action, like that of other nonsteroidal anti-inflammatory drugs, is not fully
understood.
Ketoprofen is a racemate with only the S enantiomer possessing
pharmacological activity. The enantiomers have similar concentration time curves and
do not appear to interact with one another. An analgesic effect-concentration
relationship for ketoprofen was established in an oral surgery pain study with Orudis.
The effect-site rate constant was estimated to be 0.9 hour (95% confidence limits: 0 to
2.1), and the concentration (Ceg of Ketoprofen that produced one-half the maximum
PID (pain intensity difference) was 0.3 µg/mLs (9596 confidence limits: 0.1 to 0.5).
Thirty-three (33) to 68% of patients had an onset of action (as measured by reporting
some pain relief) within 30 minutes following a single oral dose in postoperative pain
and dysmenorrhea studies. Pain relief (as measured by remedication) persisted for up
to 6 hours in 26 to 7296 of patients in these studies.

Indications:
Ketoprofen is indicated for the management of the signs and symptoms of
rheumatoid arthritis and osteoarthritis.
Adverse effects:
Ketoprofen causes gastrointestinal disturbances such as intestinal bleeding,
epigastric pain, nausea, sensation of fullness in stomach and heartburns. Less
frequently, they may cause CNS symptoms such as headache, dizziness, blurred
vision, tinnitus, urticaria and insomnia. In few cases fluid retention and edema occurs.
Jaundice, impairment of renal function and thrombocytopenia occurs rarely.
Administration and Dose:
Ketoprofen administered orally 50-100 mg twice daily, with food. Ketoprofen
suppository 100 mg once a day.
Contraindication:
• Allergy to aspirin or other NSAID’s.
• History of ulcer disorder.
• Severe impairment of kidney function.
• Bleeding or blood cell disorder.
• Combination of ketoprofen with warfarin is not recommended.
• Combination of ketoprofen with probencid is not recommended.
Uses:
Ketoprofen is used in treatment of rheumatoid arthritis, osteoarthritis,
dysmenorrhea and management of pain.
Brand name:
Orudis, Oruvail, Profenid, Fastum, Ketopron, Kefinid.

3.3. EXCIPIENTS REVIEW
3.3.1. CROSCARMELLOSE SODIUM 86
Synonyms
Ac-Di-Sol; cross-linked carboxymethylcellulose sodium; Explocel.
Chemical Name and CAS Registry Number
Cellulose, carboxymethyl ether, sodium salt, cross-linked [74811-65-7]
Empirical Formula and Molecular Weight
The USP 28 describes carboxymethylcellulose sodium as the sodium salt of a
polycarboxymethyl ether of cellulose. Typical molecular weight is 90 000–700 000.
Applications in Pharmaceutical Formulation or Technology
Croscarmellose sodium is used in oral pharmaceutical formulations as a
disintegrant for capsules, tablets, and granules. In tablet formulations, croscarmellose
sodium may be used in both direct-compression and wet-granulation processes. When
used in wet granulations, the croscarmellose sodium should be added in both the wet
and dry stages of the process (intra- and extragranularly) so that the wicking and
swelling ability of the disintegrant is best utilized. Croscarmellose sodium at
concentrations up to 5% w/w may be used as a tablet disintegrant, although normally
2% w/w is used in tablets prepared by direct compression and 3% w/w in tablets
prepared by a wet-granulation process.
Description
Croscarmellose sodium occurs as an odorless, white or grayish-white powder.

Table-4: Typical Properties of Croscarmellose Sodium.
S. No. Properties Value
1 Density (Bulk) 0.529 g/cm3
2 Density (Tapped) 0.819 g/cm3
3 Density (True) 1.543 g/cm3
4 Solubility Insoluble in water but rapidly swells up to 4-8 times

its original volume and also insoluble acetone,
ethanol and toluene
Stability and Storage Conditions
A model tablet formulation prepared by direct compression, with
croscarmellose sodium as a disintegrant, showed no significant difference in drug
dissolution after storage at 30°C for 14 months. Croscarmellose sodium should be
stored in a well-closed container in a cool, dry place.
Incompatibilities
Croscarmellose sodium is not compatible with strong acids or with soluble
salts of iron and some other metals such as aluminum, mercury, and zinc.

3.3.2. SODIUM STARCH GLYCOLATE 87
Synonyms
Carboxymethyl starch, sodium salt; Explosol; Glycolys.
Sodium carboxymethyl starch [9063-38-1]
It is widely used in oral pharmaceuticals as a disintegrant in capsule and tablet
formulations. It is commonly used in tablets prepared by either direct-compression or
wet-granulation processes. The usual concentration employed in a formulation is
between 2% and 8%, with the optimum concentration about 4%, although in many
cases 2% is sufficient. Disintegration occurs by rapid uptake of water followed by
rapid and enormous swelling. Although the effectiveness of many disintegrants is
affected by the presence of hydrophobic excipients such as lubricants, the disintegrant
efficiency of sodium starch glycolate is unimpaired. Increasing the tablet compression
pressure also appears to have no effect on disintegration time. Sodium starch
glycolate has also been investigated for use as a suspending vehicle.
Description
Sodium starch glycolate is a white to off-white, odorless, tasteless, free-
flowing powder. The PhEur 2005 states that it consists of oval or spherical granules,
30–100 μm in diameter, with some less-spherical granules ranging from 10–35 μm in
diameter.

Table-5: Typical Properties of Sodium Starch Glycolate
1 Density (Bulk) 0.756g/cm3
2 Density (Tapped) 0.945 g/cm3
3 Density (True) 1.443 g/cm3
4 Solubility Sparingly soluble in ethanol;
Practically insoluble in water.
Tablets prepared with sodium starch glycolate have good storage properties.
Sodium starch glycolate is stable and should be stored in a well-closed container in
order to protect it from wide variations of humidity and temperature, which may cause
caking. The physical properties of sodium starch glycolate remain unchanged for up
to 3–5 years if it is stored at moderate temperatures and humidity.
Incompatibilities
Sodium starch glycolate is incompatible with ascorbic acid.

3.3.3. CROSPOVIDONE88
Synonyms
Cross-linked povidone; Kollidon CL; Polyplasdone XL.
1-Ethenyl-2-pyrrolidinone homopolymer [9003-39-8]
Crospovidone is a water-insoluble tablet disintegrant and dissolution agent
used at 1–5% concentration in tablets prepared by direct-compression or wet- and dry-
granulation methods. It rapidly exhibits high capillary activity and pronounced
hydration capacity, with little tendency to form gels. Studies suggest that the particle
size of crospovidone strongly influences disintegration of analgesic tablets. Larger
particles provide a faster disintegration than smaller particles. Crospovidone can also
be used as a solubility enhancer.
Description
Crospovidone is a white to creamy-white, finely divided, free-flowing,
practically tasteless, odorless or nearly odorless, hygroscopic powder.
Table-6: Typical Properties of Crosspovidone
1 Density 1.22 g/cm3
2 Solubility Insoluble in water and most

common organic solvents

Since crospovidone is hygroscopic, it should be stored in an airtight container
in a cool, dry place.
Incompatibilities
Crospovidone is compatible with most organic and inorganic pharmaceutical
ingredients. When exposed to a high water level, crospovidone may form molecular
adduct with some materials.
3.3.4. SODIUM BICARBONATE 89
Synonyms
Baking soda; sodium acid carbonate; sodium hydrogen carbonate.
Carbonic acid monosodium salt [144-55-8]
NaHCO3 84.01
Structural Formula
NaHCO3
Functional Category
Alkalizing agent; therapeutic agent.

Sodium bicarbonate is generally used in pharmaceutical formulations as a
source of carbon dioxide in effervescent tablets and granules. It is also widely
used to produce or maintain an alkaline pH in a preparation. In effervescent
tablets and granules, sodium bicarbonate is usually formulated with citric and/or
tartaric acid; combinations of citric and tartaric acid are often preferred in
formulations as citric acid alone produces a sticky mixture that is difficult to
granulate, while if tartaric acid is used alone, granules lose firmness. When the
tablets or granules come into contact with water, a chemical reaction occurs,
carbon dioxide is evolved, and the product disintegrates. Tablets may also be
prepared with sodium bicarbonate alone since the acid of gastric fluid is
sufficient to cause effervescence and disintegration. Sodium bicarbonate is also
used in tablet formulations to buffer drug molecules that are weak acids, thereby
increasing the rate of tablet dissolution and reducing gastric irritation.
Description
Sodium bicarbonate occurs as an odorless, white, crystalline powder with
a saline, slightly alkaline taste. The crystal structure is monoclinic prisms.
Grades with different particle sizes, from a fine powder to free-flowing uniform
granules, are commercially available.
Typical Properties
Acidity/alkalinity:
pH = 8.3 for a freshly prepared 0.1 M aqueous solution at 25°C;
alkalinity increases on standing, agitation, or heating.

Density (bulk): 0.869 g/cm3
Density (tapped): 1.369 g/cm3
Density (true): 2.173 g/cm3
Solubility
Practically soluble in water and most common organic solvents.
When heated to about 50°C, sodium bicarbonate begins to dissociate into
carbon dioxide, sodium carbonate, and water; on heating to 250–300°C, for a
short time, sodium bicarbonate is completely converted into anhydrous sodium
carbonate. However, the process is both time- and temperature-dependent, with
conversion 90% complete within 75 minutes at 93°C. The reaction proceeds via
surface-controlled kinetics; when sodium bicarbonate crystals are heated for a
short period of time, very fine needle-shaped crystals of anhydrous sodium
carbonate are formed on the sodium bicarbonate surface.
Incompatibilities
Sodium bicarbonate reacts with acids, acidic salts, and many alkaloidal
salts, with the evolution of carbon dioxide. Sodium bicarbonate can also
intensify the darkening of salicylates. In powder mixtures, atmospheric moisture
or water of crystallization from another ingredient is sufficient for sodium
bicarbonate to react with compounds such as boric acid or alum. In liquid
mixtures containing bismuth subnitrate, sodium bicarbonate reacts with the acid
formed by hydrolysis of the bismuth salt.

3.3.5. CITRIC ACID MONOHYDRATE 90
Synonyms
E330; 2-hydroxypropane-1, 2, 3-tricarboxylic acid monohydrate.
2-Hydroxy-1, 2, 3-propanetricarboxylic acid monohydrate [5949-29-1]
C6H8O7·H2O 210.14
Structural Formula
Functional Category
Acidifying agent; antioxidant; buffering agent; chelating agent; flavor
enhancer.
Citric acid (as either the monohydrate or anhydrous material) is widely
used in pharmaceutical formulations and food products, primarily to adjust the
pH of solutions. It has also been used experimentally to adjust the pH of tablet
matrices in enteric-coated formulations for colon-specific drug delivery. Citric
acid monohydrate is used in the preparation of effervescent granules, while
anhydrous citric acid is widely used in the preparation of effervescent tablets.

Citric acid has also been shown to improve the stability of spray-dried insulin
powder in inhalation formulations.
In food products, citric acid is used as a flavor enhancer for its tart, acidic
taste. Citric acid monohydrate is used as a sequestering agent and antioxidant
synergist.
It is also a component of anticoagulant citrate solutions. Therapeutically,
preparations containing citric acid have been used to dissolve renal calculi.
Description
Citric acid monohydrate occurs as colorless or translucent crystals, or as a
white crystalline, efflorescent powder. It is odorless and has a strong acidic taste.
The crystal structure is orthorhombic.
Typical Properties
Acidity/alkalinity: pH = 2.2 (1% w/v aqueous solution)
Density: 1.542 g/cm3
Solubility:
Soluble 1 in 1.5 parts of ethanol (95%) and 1 in less than 1 part of water
sparingly soluble in ether.
Citric acid monohydrate loses water of crystallization in dry air or when
heated to about 40°C. It is slightly deliquescent in moist air. Dilute aqueous
solutions of citric acid may ferment on standing.
The bulk monohydrate or anhydrous material should be stored in airtight
containers in a cool, dry place.

Incompatibilities
Citric acid is incompatible with potassium tartrate, alkali and alkaline
earth carbonates and bicarbonates, acetates, and sulfides. Incompatibilities also
include oxidizing agents, bases, reducing agents, and nitrates. It is potentially
explosive in combination with metal nitrates. On storage, sucrose may crystallize
from syrups in the presence of citric acid.
3.3.6. PEG – 6000 91
Synonyms:
Carbowax; Carbowax Sentry; Lipoxol; Lutrol E; PEG; Pluriol E;
polyoxyethylene glycol.
Chemical Name and CAS Registry Number:
a-Hydro-o-hydroxypoly (oxy-1,2-ethanediyl)
Empirical Formula and Molecular Weight:
HOCH2(CH2OCH2)mCH2OH where m represents the average number of
oxyethylene groups.
Structural Formula:
Functional Category:
Ointment base; plasticizer; solvent; suppository base; tablet and capsule
lubricant.

Applications in Pharmaceutical Formulation or Technology:
Polyethylene glycols can also be used to enhance the aqueous solubility or
dissolution characteristics of poorly soluble compounds by making solid dispersions
with an appropriate polyethylene glycol. Polyethylene glycol grades with molecular
weights of 6000 and above can be used as lubricants, particularly for soluble tablet. In
solid-dosage formulations, higher-molecular-weight polyethylene glycols can enhance
the effectiveness of tablet binders and impart plasticity to granules.(4) However, they
have only limited binding action when used alone, and can prolong disintegration if
present in concentrations greater than 5% w/w. When used for thermoplastic
granulations, (5–7) a mixture of the powdered constituents with 10–15% w/w PEG
6000 is heated to 70–758C. The mass becomes paste like and forms granules if stirred
while cooling. This technique is useful for the preparation of dosage forms such as
lozenges when prolonged disintegration is required.
Description:
The USPNF 23 describes polyethylene glycol as being an addition polymer of
ethylene oxide and water. Polyethylene glycol grades 200–600 are liquids; grades
1000 and above are solids at ambient temperatures. Solid grades (PEG>1000) are
white or off-white in color, and range in consistency from pastes to waxy flakes. They
have a faint, sweet odor. Grades of PEG 6000 and above are available as free-flowing
milled powders.
Typical Properties:
Density:
1.11–1.14 g/cm3 at 258C for liquid PEGs;
1.15–1.21 g/cm3 at 258C for solid PEGs.

Melting point:
55–630C for PEG 6000;
Solubility:
All grades of polyethylene glycol are soluble in water and miscible in all
proportions with other polyethylene glycols (after melting, if necessary) Solid
polyethylene glycols are soluble in acetone, dichloromethane, ethanol (95%),and
methanol; they are slightly soluble in aliphatic hydrocarbons and ether, but insoluble
in fats, fixed oils, and mineral oil.
Stability and Storage Conditions:
Polyethylene glycols are chemically stable in air and in solution, although
grades with a molecular weight less than 2000 are hygroscopic. Polyethylene glycols
do not support microbial growth, and they do not become rancid. Polyethylene glycols
should be stored in well-closed containers in a cool, dry place
Incompatibilities:
All grades can exhibit some oxidizing activity owing to the presence of
peroxide impurities and secondary products formed by autoxidation. Liquid and solid
polyethylene glycol grades may be incompatible with some coloring agents.

3.3.7. PVP K30 92
Synonyms:
E1201; Kollidon; Plasdone; poly[1-(2-oxo-1-pyrrolidinyl)ethylene];
polyvidone; polyvinylpyrrolidone; PVP; 1-vinyl-2-pyrrolidinone polymer.
Chemical Name and CAS Registry Number:
1-Ethenyl-2-pyrrolidinone homopolymer (9003-39-8)
Empirical Formula and Molecular Weight:
(C6H9NO)n 2500–3000000
PVP K 30: 50000
Structural Formula:
Functional Category:
Disintegrant; dissolution aid; suspending agent; tablet binder.
Applications in Pharmaceutical Formulation or Technology:
Although povidone is used in a variety of pharmaceutical formulations, it is
primarily used in solid-dosage forms. In tableting, povidone solutions are used as
binders in wet granulation processes.(2,3) Povidone is also added to powder blends in
the dry form and granulated in situ by the addition of water, alcohol, or
hydroalcoholic solutions. Povidone is used as a solubilizer in oral and parenteral
formulations and has been shown to enhance dissolution of poorly soluble drugs from
solid-dosage forms.(4–6) Povidone solutions may also be used as coating agents.
Povidone is additionally used as a suspending, stabilizing, or viscosity-increasing

agent in a number of topical and oral suspensions and solutions. The solubility of a
number of poorly soluble active drugs may be increased by mixing with povidone.
Description:
Povidone occurs as a fine, white to creamy-white colored, odorless or almost
odorless, hygroscopic powder. Povidones with K-values equal to or lower than 30 are
manufactured by spray-drying and occur as spheres. Povidone K-90 and higher K-
value povidones are manufactured by drum drying and occur as plates.
Typical Properties:
Acidity/alkalinity: pH = 3.0–7.0 (5% w/v aqueous solution).
Density (bulk): 0.29–0.39 g/cm3 for Plasdone.
Density (tapped): 0.39–0.54 g/cm3 for Plasdone.
Flowability: 20 g/s for povidone K-15;
16 g/s for povidone K-29/32.
Melting point:
Softens at 1500C.
Moisture content:
Povidone is very hygroscopic, significant amounts of moisture being absorbed
at low relative humidities.
Solubility:
Freely soluble in acids, chloroform, ethanol (95%), ketones, methanol, and
water; practically insoluble in ether, hydrocarbons, and mineral oil. In water, the
concentration of a solution is limited only by the viscosity of the resulting solution,
which is a function of the K-value.

Viscosity (dynamic):
The viscosity of aqueous povidone solutions depends on both the
concentration and the molecular weight of the polymer employed. PVP K 30
Viscosity (dynamic) is 5.5–8.5
Povidone darkens to some extent on heating at 1508C, with a reduction in
aqueous solubility. It is stable to a short cycle of heat exposure around 110–1308C.
Povidone may be stored under ordinary conditions without undergoing decomposition
or degradation. However, since the powder is hygroscopic, it should be stored in an
airtight container in a cool, dry place.
Incompatibilities
Povidone is compatible in solution with a wide range of inorganic salts,
natural and synthetic resins, and other chemicals. It forms molecular adducts in
solution with sulfathiazole, sodium salicylate, salicylic acid, phenobarbital, tannin,
and other compounds. The efficacy of some preservatives, e.g. thimerosal, may be
adversely affected by the formation of complexes with povidone.
3.3.8. CELLULOSE, MICROCRYSTALLINE 93
Synonyms
Avicel PH; Celex; cellulose gel; Celphere; Ceolus KG; crystalline cellulose;
E460; Emcocel; Ethispheres; Fibrocel; Pharmacel; Tabulose; Vivapur.
Cellulose [9004-34-6]

(C6H10O5)n = 36000.
Where n = 220.
Structural Formula
Functional Category
Adsorbent; suspending agent; tablet and capsule diluent; tablet disintegrant.
Microcrystalline cellulose is widely used in pharmaceuticals, primarily as a
binder/diluent in oral tablet and capsule formulations where it is used in both wet-
granulation and direct-compression processes. In addition to its use as a
binder/diluent, microcrystalline cellulose also has some lubricant and disintegrant
properties that make it useful in tableting.
Microcrystalline cellulose is also used in cosmetics and food products.

Description
Microcrystalline cellulose is purified, partially depolymerized cellulose that
occurs as a white, odorless, tasteless, crystalline powder composed of porous
particles. It is commercially available in different particle sizes and moisture grades
that have different properties and applications.
Typical Properties
Angle of repose:
• 49° for Ceolus KG;
• 34.4° for Emcocel 90M.
Density (bulk):
3
• 0.337 g/cm ;
3
• 0.32 g/cm for Avicel PH-101;
3
• 0.29 g/cm for Emcocel 90M;
3
• 0.29 g/cm for VivaPur 101.
Density (tapped):
3
• 0.478 g/cm ;
3
• 0.45 g/cm for Avicel PH-101;
3
• 0.35 g/cm for Emcocel 90M.
Density (true):
1.512–1.668 g/cm3
Flowability:
1.41 g/s for Emcocel 90M.

Solubility:
Slightly soluble in 5% w/v sodium hydroxide solution; practically insoluble in
water, dilute acids, and most organic solvents.
Microcrystalline cellulose is a stable though hygroscopic material. The bulk
material should be stored in a well-closed container in a cool, dry place.
Incompatibilities
Microcrystalline cellulose is incompatible with strong oxidizing agents.
3.3.9. ANHYDROUS LACTOSE 94
Synonyms
Pharmatose DCL 22; saccharum lactis; Super-Tab Anhydrous.
O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranose [63-42-3]
C12H22O11 , 342.30

Structural Formula
The PhEur 2005 describes anhydrous lactose as O-β-D-galactopyranosyl-
(1→4)-β-D-glucopyranose; or a mixture of O-β-D-galactopyranosyl-(1→4)-α-D-
glucopyranose and O-β-D-galactopyranosyl-(1→4)-β-D-glucopyranose. The
USPNF 23 describes anhydrous lactose as being primarily β-lactose or a mixture
of α- and β-lactose. The JP 2001 describes anhydrous lactose as β-lactose or a
mixture of β-lactose and α-lactose.
Functional Category
Binding agent; directly compressible tableting excipient; lyophilization
aid; tablet and capsule filler.
Anhydrous lactose is widely used in direct compression tableting
applications and as a tablet and capsule filler and binder. Anhydrous lactose can
be used with moisture-sensitive drugs due to its low moisture content.

Description
Lactose occurs as white to off-white crystalline particles or powder.
Several different brands of anhydrous lactose are commercially available which
contain anhydrous β-lactose and anhydrous α-lactose. Anhydrous lactose
typically contains 70–80% anhydrous β-lactose and 20–30% anhydrous α-
lactose.
Typical Properties
Density (true): 1.589 g/cm3 for anhydrous β-lactose;
Density (bulk):0.68 g/cm3 for Pharmatose DCL 21;
Density (tapped):0.88 g/cm3 for Pharmatose DCL 21;
Solubility
Soluble in water; sparingly soluble in ethanol (95%) and ether.
Mold growth may occur under humid conditions (80% RH and above).
Lactose may develop a brown coloration on storage, the reaction being
accelerated by warm, damp conditions. At 80°C and 80% RH, tablets containing
anhydrous lactose have been shown to expand 1.2 times after one day.
Lactose anhydrous should be stored in a well-closed container in a cool, dry
place.
Incompatibilities
Lactose anhydrous is incompatible with strong oxidizers. When mixtures
containing a hydrophobic leukotriene antagonist and anhydrous lactose or lactose
monohydrate were stored for six weeks at 40°C and 75% RH, the mixture

containing anhydrous lactose showed greater moisture uptake and drug
degradation.
Studies have also shown that in blends of roxifiban acetate (DMP-754)
and lactose anhydrous, the presence of lactose anhydrous accelerated the
hydrolysis of the ester and amidine groups.
3.3.10 DEXTROSE 95
Synonyms
Corn sugar; D-(+)-glucopyranose monohydrate; grape sugar;
D-(+)-Glucose monohydrate [5996-10-1]
C6H12O6·H2O 198.17 (for monohydrate)
Structural Formula
Anhydrous material shown.

Functional Category
Tablet and capsule diluent; therapeutic agent; tonicity agent; sweetening
agent.
Dextrose is widely used in solutions to adjust tonicity and as a
sweetening agent. Dextrose is also used as a wet granulation diluent and binder,
and as a direct-compression tablet diluent and binder, primarily in chewable
tablets. Although dextrose is comparable as a tablet diluent to lactose, tablets
produced with dextrose monohydrate require more lubrication, are less friable,
and have a tendency to harden. The mildly reducing properties of dextrose may
be used when tableting to improve the stability of active materials that are
sensitive to oxidation.
Description
Dextrose occurs as odorless, sweet-tasting, colorless crystals or as a white
crystalline or granular powder. The JP 2001 describes dextrose as dextrose
anhydrous; the PhEur 2005 specifies dextrose as either dextrose anhydrous or
dextrose monohydrate; and the USP 28 specifies dextrose as dextrose
monohydrate.
Typical Properties
Acidity/alkalinity: pH = 3.5–5.5 (20% w/v aqueous solution)
Density (bulk):0.826 g/cm3
Density (tapped):1.020 g/cm3
Density (true):1.54 g/cm3

Solubility:
Soluble in water; sparingly soluble in ethanol (95%) and ether.
Dextrose has good stability under dry storage conditions. Aqueous
solutions may be sterilized by autoclaving. However, excessive heating can
cause a reduction in pH and caramelization of solutions.
The bulk material should be stored in a well-closed container in a cool,
dry place.
Incompatibilities
Dextrose solutions are incompatible with a number of drugs such as
cyanocobalamin, kanamycin sulfate, novobiocin sodium, and warfarin sodium.
Erythromycin gluceptate is unstable in dextrose solutions at a pH less than 5.05.
Decomposition of B-complex vitamins may occur if they are warmed with
dextrose.
In the aldehyde form, dextrose can react with amines, amides, amino
acids, peptides, and proteins. Brown coloration and decomposition occur with
strong alkalis.
3.3.11 MAGNESIUM STEARATE 96
Synonyms
Magnesium octadecanoate; octadecanoic acid, magnesium salt; stearic acid,
magnesium salt.

Octadecanoic acid magnesium salt [557-04-0]
C36H70MgO4 ,591.34
The USPNF 23 describes magnesium stearate as a compound of magnesium
with a mixture of solid organic acids that consists chiefly of variable proportions of
magnesium stearate and magnesium palmitate (C32H62MgO4). The PhEur 2005
describes magnesium stearate as a mixture of magnesium salts of different fatty acids
consisting mainly of stearic acid and palmitic acid and in minor proportions other
fatty acids.
Structural Formula
[CH3(CH2)16COO]2Mg
Functional Category
Tablet and capsule lubricant.
Magnesium stearate is widely used in cosmetics, foods, and pharmaceutical
formulations. It is primarily used as a lubricant in capsule and tablet manufacture at
concentrations between 0.25% and 5.0% w/w. It is also used in barrier creams.

Description
Magnesium stearate is a very fine, light white, precipitated or milled,
impalpable powder of low bulk density, having a faint odor of stearic acid and a
characteristic taste. The powder is greasy to the touch and readily adheres to the skin.
Typical Properties
Crystalline forms: high-purity magnesium stearate has been isolated as a
trihydrate, a dihydrate, and an anhydrate.
Density (bulk): 0.159 g/cm3
Density (tapped): 0.286 g/cm3
Magnesium stearate is stable and should be stored in a well-closed container in
a cool, dry place.
Incompatibilities
Incompatible with strong acids, alkalis, and iron salts. Avoid mixing with
strong oxidizing materials. Magnesium stearate cannot be used in products containing
aspirin, some vitamins, and most alkaloidal salts.

3.3.12. TALC 97
Synonyms
Altalc; E553b; hydrous magnesium calcium silicate; hydrous magnesium
silicate; Luzenac Pharma; magnesium hydrogen metasilicate; Magsil Osmanthus;
Magsil Star; powdered talc; purified French chalk; Purtalc; soapstone; steatite;
Superiore.
Talc [14807-96-6]
Talc is a purified, hydrated, magnesium silicate, approximating to the formula
Mg6(Si2O5)4(OH)4. It may contain small, variable amounts of aluminum silicate and
iron.
Structural Formula
Mg6 (Si2O5)4(OH)4.
Functional Category
Anticaking agent; glidant; tablet and capsule diluents; tablet and capsule
lubricant.

¾ Talc was once widely used in oral solid dosage formulations as a lubricant and
diluent, although today it is less commonly used. However, it is widely used as
a dissolution retardant in the development of controlled-release products. Talc
is also used as a lubricant in tablet formulations; in a novel powder coating for
extended-release pellets; and as an adsorbent.
¾ In topical preparations, talc is used as a dusting powder, although it should not
be used to dust surgical gloves;. Talc is a natural material; it may therefore
frequently contain microorganisms and should be sterilized when used as a
dusting powder;
¾ Talc is additionally used to clarify liquids and is also used in cosmetics and
food products, mainly for its lubricant properties.
Description
Talc is a very fine, white to grayish-white, odorless, impalpable, unctuous,
crystalline powder. It adheres readily to the skin and is soft to the touch and free from
grittiness.
Typical Properties
Acidity/alkalinity: pH = 7–10 for a 20% w/v aqueous dispersion.
Hardness (Mohs): 1.0–1.5
Solubility:
Practically insoluble in dilute acids and alkalis, organic solvents, and water.

Talc is a stable material and may be sterilized by heating at 160°C for not less
than 1 hour. It may also be sterilized by exposure to ethylene oxide or gamma
irradiation.
Talc should be stored in a well-closed container in a cool, dry place.
Incompatibilities
Incompatible with quaternary ammonium compounds.

METHODOLOGY
CHAPTER-4.
METHODOLOGY
4.1 MATERIALS
Table 7. List of Materials
S. No. Name Manufacturer

1 Ketoprofen Concept Pharmaceuticals, Aurangabad.
2 Polyvinylpyrollidone K-30 M/s Healer’s Lab.Pvt.Ltd. Baddi.

3 Polyvinylglycol-6000 S.D.Fine Pvt.Ltd., Mumbai
4 Ac-Di-Sol M/s Healer’s Lab.Pvt.Ltd. Baddi
5 Sodium Starch Glycolate M/s Healer’s Lab.Pvt.Ltd. Baddi
6 Crospovidone M/s Healer’s Lab.Pvt.Ltd. Baddi
7 Sodium Bicarbonate S.D.Fine Pvt.Ltd., Mumbai
8 Citric Acid S.D.Fine Pvt.Ltd., Mumbai
9 Avicel PH 102 M/s Healer’s Lab.Pvt.Ltd. Baddi
10 Lactose M/s Healer’s Lab.Pvt.Ltd. Baddi
11 Dextrose M/s Healer’s Lab.Pvt.Ltd. Baddi
12 Magnesium Stearate S.D.Fine Pvt.Ltd., Mumbai
13 Talc S.D.Fine Pvt.Ltd., Mumbai
14 Cardamom flavor Chemwell Pvt.Ltd.,Bangalore
15 Sodium Phosphate S.D.Fine Pvt.Ltd., Mumbai
16 Sodium Hydroxide S.D.Fine Pvt.Ltd., Mumbai
17 Methanol LR S.D. Fine Chem. Ltd., Mumbai
18 Acetone LR S.D. Fine Chem. Ltd., Mumbai
19 Aluminium Foil Hindalco Industries Ltd., Silvasa

METHODOLOGY
4.2. EQUIPMENT:
Table 8: List of Equipment Used
SR.
EQUIPMENTS COMPANY NAME
NO.
UV/VIS Double beam
1 Shimadzu 1700, Japan
Spectrophotometer
FTIR
2 Jasco FTIR 6100 type-A, Japan
Magnetic Stirrer
3 Remi Instrument Pvt Ltd., Mumbai
USP Tablet dissolution apparatus
4 Lab India Disso 2000
type II
10 Station rotary punch tableting
5 Riemek Minipress, Ahmedabad
machine
Hot air oven
6 EIE Instrument Pvt. Ltd., Ahmedabad
pH meter
7 Eutech, Singapur
Digital Weighing balance
8 Adair Dutt Instrument Pvt. Ltd.
Hardness tester
9 Pfizer hardness tester, Mumbai
Friability tester
10 Veego friability tester, Mumbai
Tapped density tester
11 Electro lab
Stability apparatus
12 Paramount

METHODOLOGY
4.3 DRUG IDENTIFICATION TESTS: 98
I. Physical Appearance:
Physical appearance of drug was examined by various organoleptic properties.
II. Melting Point:
Melting point of the Ketoprofen was determined by capillary fusion method;
one sided closed capillary filled with drug and put into the Melting Point Apparatus.
Temperature was noted at which solid drug changed into liquid.
III. Infrared Spectral Assignment:
The pellet of approximately 01 mm diameter of the drug was prepared
grinding 3-5 mg of sample with 100-150 mg of Potassium Bromide using hydrostatic
press. The sample pellet was mounted in IR compartment and scanned at wavelength
4000 cm-1 – 500 cm-1. On analysis of the IR spectra of the reference spectra (A) given
in Indian Pharmacopoeia (1996) and pure drug (B), no major differences were
observed in the characteristic absorption peak (1696, 1655) pattern. The results were
shown in Figure 10 (A) and 11 (B).
IV. Differential Scanning Calorimetry (DSC):
DSC analysis was performed on 5 mg sample. Samples were heated in an open
aluminum pans at a rate of 100 per min–1 in a 30 to 3000C temperature range under a
nitrogen flow of 40 mL/min. It shows endothermic peak at about 94.120C Figure 12.
V. Ultraviolet Absorption Maxima:
Ultraviolet absorption in the rage 200 to 400 nm of a 5μg/ml solution in 5%
(v/v) methanolic Sorenson’s Buffer (pH 6.8) was measured. The absorption maxima

METHODOLOGY
(λmax) of Ketoprofen (5 µg/ml) in this solution was found to be 260 nm which is
concordant with the Indian Pharmacopoeia (1996) shown in Figure 13.
4.4. PREFORMULATION STUDIES: 99
4.4.1 Solubility:
The solubility of Ketoprofen was determined in different solvent systems and
buffers. An excess quantity of the drug was mixed with 10 ml of each solvent in
screw capped glass tubes and shaken on constant water bath shaker for 24 hours at
25o. The solutions were examined physically for the absence or presence of drug
particles and also by spectrophometrically for quantitative determination of drug in
buffers. The results were shown in Table 22.
4.4.2 Preparation of Calibration Curve:
(a) Preparation of Sorenson’s Buffer (pH 6.8):
24.5 ml of 0.2 M dibasic sodium phosphate and 25.5 ml of 0.2 M monobasic
sodium phosphate was placed in 100 ml volumetric flask and make up the volume 100
ml with water.
(b) Calibration Curve:
50 mg of Ketoprofen was weighed accurately and dissolved in 5 ml of
methanol in a 100 ml of volumetric flask and volume was made up to 100 ml with the
Sorenson’s buffer (pH 6.8). 10 ml of this solution was diluted with 100 ml Sorenson’s
buffer (pH 6.8) to obtain a stock solution of 50µg/ml. From this stock solution,
aliquots of 1 ml, 2 ml, 3 ml, 4 ml and 5 ml were taken transferred to 10 ml volumetric
flask and volume was made up to 10 ml with Sorenson’s buffer (pH 6.8). The
absorbance of these solutions was measured at 260 nm against a blank Sorenson’s

METHODOLOGY
buffer (pH 6.8). The calibration curve was plotted between concentration and
absorbance.
4.4.3 Drug Polymer Interaction Studies:
The infrared absorption spectra of pure polymer and physical mixture of
polymer and drug were performed for polymer drug interaction studies. Fourier
Transform Infrared spectra were recorded on samples prepared in potassium bromide
(KBr) disks. Samples were prepared in KBr disks by means of a hydrostatic press.
The scanning range was 400 to 4000 cm–1 and the resolution was 4 cm–1. The IR
spectra of physical mixture of polymers and drug were shown in Figure 15-20.
4.5. PREPARATION OF PHYSICAL MIXTURES OF KETOPROFEN:
Physical mixtures of Ketoprofen were prepared using Polyvinylpyrollidone k-
30 and Polyvinylglycol-6000 as a carrier in a weight ratio. First drug and carrier were
passed through a 40 mesh screen and then weighed and mixed by using motor and
pestle (Table 9 & 10).
Table-9: Composition of Ketoprofen-PVP K-30 Physical Mixture.
Sr.No. Formulation Drug : Carrier

Number Weight Ratio
1 KP1 1:1
2 KP2 1:2
3 KP3 1:3
Table-10: Composition of Ketoprofen-PEG-6000 Physical Mixture.

Number Weight Ratio
1 KPG1 1:1
2 KPG2 1:2
3 KPG3 1:3

METHODOLOGY
4.6. PREPARATION OF SOLID DISPERSIONS OF KETOPROFEN:100
Ketoprofen solid dispersions were prepared by solvent evaporation method
using carriers (i.e. PVP K-30, PEG-6000) in proportions, viz. 1:1, 1:2, 1:3 (Drug:
Carrier). Methanol is selected as common solvent for solid dispersion. The respective
amount of carrier was dissolved in methanol 20 ml and ketoprofen was added in parts
with continuous stirring. The solvent was then removed by evaporation. The prepared
solid dispersion were pulverized and shifted through sieve no. 100 and stored over a
fused calcium chloride in a desiccator for further use.
Table-11: Composition of Ketoprofen-PVP K-30 Solid Dispersions.

Number Weight Ratio
1 KPVP1 1:1
2 KPVP2 1:2
3 KPVP3 1:3
Table-12: Composition of Ketoprofen-PEG-6000 Solid Dispersions.

Number Weight Ratio
1 KPEG1 1:1
2 KPEG2 1:2
3 KPEG3 1:3

METHODOLOGY
4.7. EVALUATION OF PHYSICAL MIXTURES AND SOLID DISPERSIONS:

101
The prepared physical mixtures and solid dispersions were evaluated for
solubility studies, percent drug content, dissolution efficiency, in-vitro drug release
and Fourier transform infrared (FTIR), Differential scanning calorimetry (DSC), X-
ray diffraction (XRD), scanning electron microscopy (SEM),
4.7.1. . Determination of Solubility of Solid Dispersions:
Ketoprofen, physical mixtures or solid dispersions equivalent to 10 mg of
Ketoprofen were added to 10 ml of Sorenson’s buffer pH 6.8 in a 10 ml volumetric
flask. The volumetric flasks were capped properly and shaken at 250 and 370 C in a
temperature controlled water bath (Shaking water bath) for 48 h. Resultant samples
containing undissolved solid dispersions suspended in the volumetric flask were
filtered through 0.45μm filters, suitably diluted with Sorenson’s buffer pH 6.8 and
analyzed by UV spectrophotometer at 260 nm.
4.7.2 Determination of Drug Content:
Drug content was calculated by dissolving solid dispersions equivalent to 100
mg Ketoprofen in 10 ml of methanol, filtered using 0.45μm Whatman filter paper,
suitably diluted with Sorenson’s buffer (pH 6.8) and analyzed by using UV
spectrophotometer against Sorenson’s buffer as blank.
4.7.3 In-vitro Drug Release:
Accurately weighed preparations equivalent to 100 mg of Ketoprofen were
added to 900 ml of dissolution medium in USP II Paddle type apparatus and stirred at
speed of 50 rpm at 37 ± 0.50 C. 5 ml aliquots were withdrawn at 5, 10, 15, 30, 45, 60

METHODOLOGY
minutes and replaced by 5 ml of fresh dissolution media. The collected samples were
analyzed after filtration and dilution at 260 nm using UV-visible spectrophotometer
against the blank. Drug release studies were carried out in triplicate. The dissolution
of pure Ketoprofen was done similarly. The release profile data was analyzed for
cumulative percent dissolved at different time intervals and for dissolution efficiency
at 15 and 30 minutes.
4.7.4. Fourier Transform Infrared Spectroscopy:
Fourier Transform Infrared spectra were recorded on samples prepared in
potassium bromide (KBr) disks. Samples were prepared in KBr disks by means of a
hydrostatic press. The scanning range was 400 to 4000 cm–1 and the resolution was 4
cm–1.
4.7.5. Differential Scanning Calorimetry Analysis:
Differential Scanning Calorimetry analysis was performed on 5 mg samples.
Samples were heated in an open aluminum pans at a rate of 100 per min–1 in a 30 to
300°C temperature range under a nitrogen flow of 40 mL/min.
4.7.6. X- Ray Diffraction (XRD):
XRD patterns were recorded using Philips PW 1729 X-ray generator. Powder
X-ray diffraction patterns were traced for Ketoprofen, various carriers and solid
dispersions.
4.7.7. Scanning Electron Microscopy (SEM):
The external morphology of solid dispersions was analyzed by Scanning
Electron Microscope (SEM). The samples were examined under a scanning electron
microscope JSM 6100 JEOL JAPAN.

METHODOLOGY
4.8. FORMULATION OF FAST DISSOLVING TABLETS:
Fast dissolving tablets containing selected solid dispersion were prepared by
direct compression method using single punch tablet machine to produce convex
faced tablets weighing 500 mg each with a diameter of 11 mm. A minimum of 100
tablets were prepared for each batch. The formulations were developed by using
different techniques.
4.8.1 By Addition of Super Disintegrants 102
The superdisintegrants (Croscarmallose sodium, Sodium starch glycolate and
Crospovidone) in varying concentration (1-5%) were used to develop the tablets. All
the ingredients were shown in Table 13-15 were passed through sieve no. 60 and were
co- grounded in a glass pestle motor. These blends were evaluated for mass-volume
relationship (Bulk Density, Tapped Density, Hausners Ratio, Compressibility Index)
and flow properties (Angle of Repose). The mixed blend of excipients was
compressed using a single punch tablet machine (Cadmach, Ahmedabad) to produce
convex faced tablets weighing 500 mg each with a diameter of 11 mm.
Table-13: Formulation of Fast Dissolving Tablet Using Croscarmallose sodium.
INGRADIENT F1 F2 F3 F4 F5
KPVP3 200 200 200 200 200
Crosscarmalose 5 10 15 20 25
sodium
Lactose 70 70 70 70 70
Dextrose 70 70 70 70 70
Avicel PH 102 135 130 125 120 115
Talc 10 10 10 10 10
Mg. Stearate 10 10 10 10 10
Cardamom QS QS QS QS QS
flavor

METHODOLOGY
Table-14: Formulation of Fast Dissolving Tablet Using Sodium Starch Glycolate.
KPVP3 200 200 200 200 200
Sodium starch 5 10 15 20 25
glycolate
Lactose 70 70 70 70 70
Dextrose 70 70 70 70 70
Avicel PH 102 135 130 125 120 115
Talc 10 10 10 10 10
Mg. Stearate 10 10 10 10 10
flavor
Table-15: Formulation of Fast Dissolving Tablet Using Crospovidone.

KPVP3 200 200 200 200 200
Crospovidone 5 10 15 20 25
Lactose 70 70 70 70 70
Dextrose 70 70 70 70 70
Avicel PH 102 135 130 125 120 115
Talc 10 10 10 10 10
Mg. Stearate 10 10 10 10 10
flavor
4.8.2 By Effervescence Technology
Fast dissolving tablets were prepared by using Citric acid and Sodium
bicarbonate in combination in (2:3 ratio) with other excipients shown in Table 16 was
co-grounded in glass pestle and mortar. These tablets contain (1-5%) effervescent
agent in various proportion. These blends were evaluated for mass-volume
relationship (Bulk Density, Tapped Density, Hausners Ratio, Compressibility Index)
and flow properties (Angle of Repose). The mixed blends of excipient were

METHODOLOGY
compressed using a single punch machine (Cadmach, Ahmedabad) to produce convex
faced tablets weighing 500 mg each with a diameter of 11 mm.
Table-16: Formulation of Fast Dissolving Tablet Using Effervescent Agents

KPVP3 200 200 200 200 200
Citric acid 2 4 6 8 10
Sodium 3 6 9 12 15
bicarbonate
Lactose 70 70 70 70 70
Dextrose 70 70 70 70 70
Avicel PH 102 135 130 125 120 115
Talc 10 10 10 10 10
Mg. Stearate 10 10 10 10 10
flavor
4.9. CHARACTERIZATION OF BLENDS 103
The quality of tablet, once formulated by rule, is generally dictated by the
quality of physicochemical properties of blends. There are many formulations and
process variables involved in mixing step and all these can affect the characteristics of
blend produced. The characterization of mixed blend done for the flow property of
powder that are bulk density, tapped density, Hausners ratio, Compressibility index,
angle of repose. The various characteristics of blends tested are given below and
results were shown in Table 32.
4.9.1 Bulk Density
Apparent bulk density (ρb) was determined by pouring the blend into a
graduated cylinder. The bulk volume (Vb) and weight of powder (M) was determined.
The bulk density was calculated using the formula.

METHODOLOGY
M
ρb =
Vb
4.9.2 Tapped Density
The measuring cylinder containing a known mass of blend was tapped 100
times using density apparatus. The minimum volume (Vt) occupied in the cylinder
and the weight (M) of the blend was measured. The tapped density (ρt) was calculated
using the formula.
M
ρt =
Vt
4.9.3 Compressibility Index
The simplest way for measurement of flow of powder is its compressibility, an
indication of the ease with which a material can be induced to flow is given by
compressibility index (I) which is calculated as follows
ρt − ρb
I= × 100
ρt
Where, ρt = Tapped density
ρb = Bulk density
Table-17: Compressibility Index as an Indication of Powder Flow Properties
Carr's Index (%) Type of flow

>12 Excellent
12.0-16 Good
18-21 Fair to passable
23-35 Poor
33-38 Very poor
>40 Extremely poor

METHODOLOGY
4.9.4 Hausner Ratio
Hausner ratio (HR) is an indirect index of ease of powder flow. It is calculated
by the following formula.
ρt
Hr =
ρb
Where, ρt is tapped density and ρb is bulk density.
Lower Hausner ratio (< 1.25) indicates better flow properties than higher ones (>
1.25).
4.9.5 Angle of Repose
Angle of Repose was determined using funnel method. The blend was poured
through a funnel that can be raised vertically until a specified cone height (h) was
obtained. Radius of the heap (r) was measured and angle of repose (θ) was calculated
using the formula.
h ⎛h⎞
tan θ = ; Therefore; θ = tan −1 ⎜ ⎟
r ⎝r⎠
Where, θ is angle of repose; h is height of cone; r is radius of cone
Table-18: Angle of Repose as an Indication of Powder Flow Properties.
Angle of repose(o) Type of flow

<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor

METHODOLOGY
4.10. CHARACTERIZATION OF FAST DISSOLVING TABLETS 104
After compression of powder, the tablets were evaluated for organoleptic
characteristics like color, odor, taste, diameter, thickness and physical characteristics
like hardness, friability, disintegration time, wetting time, dispersion time and
dissolution studies. The results were shown in Table 33-34.
4.10.1 General Appearance
Visual identification and over all ‘elegance’ were performed such as color,
presence or absence of an odour, taste, surface texture and physical flaws.
4.10.2 Tablet Thickness
Tablet thickness is an important characteristic in reproducing appearance and
also in counting by suing filling equipment. Some filling equipment utilizes the
uniform thickness of the tablets as a counting mechanism. Ten tablets were taken and
their thickness was recorded using micrometer (Mityato, Japan).
4.10.3 Uniformity of Weight
As per IP, twenty tablets were taken and weighted individually and
collectively using digital balance. The average weight of one tablet was calculated.
The weight variation test would be satisfactory method of determining the drug
content uniformity. Data are given in Table 19.
Table-19: Weight Variation Limits for Tablets as per IP.
Average of Tablets (mg) Maximum % difference allowed

130 or less 10
130-324 7.5
More than 324 5

METHODOLOGY
4.10.4 Hardness
Hardness of the tablet of each formulation was determined using Pfizer
hardness tester.
4.10.5 Friability
Friability of the tablets was determined using Roche friabilator. This device
subjects the tablets to the combined effect of abrasions and shock in a plastic chamber
revolving at 25 rpm and dropping the tablets at a height of 6 inch in each revolution.
Preweighed sample of tablets was placed in the friabilator and were subjected to 100
revolutions. Tablets were dedusted using a soft muslin cloth and reweighed. The
friability (F %) is determined by the formula.
⎛ Wo ⎞
F % = ⎜1 − ⎟ X 100
⎝ W ⎠
Where, W0 is initial weight of the tablets before the test and W is the weight of
the tablets after test.
4.9.6 Disintegration Test
Disintegration of fast disintegrating tablets is achieved by saliva in the mouth,
however amount of saliva in the mouth is limited and no tablet disintegration test was
found in USP and IP to simulate in vivo conditions. A modified method was used to
determine disintegration time of the tablets. A cylindrical vessel was used in which
10-mesh screen was placed in such way that only 2 ml of disintegrating or dissolution
medium would be placed below the sieve (Figure 7). To determine disintegration
time, 6 ml of Sorenson’s buffer (pH 6.8), was placed inside the vessel in such way
that 4 ml of the media was below the sieve and 2 ml above the sieve. Tablet was
placed on the sieve and the whole assembly was then placed on a shaker. The time at

METHODOLOGY
which all the particles pass through the sieve was taken as a disintegration time of the
tablet. Six tablets were chosen randomly from the composite samples and the average
value was determined.
Figure-7: Modified Device Used to Determine Disintegration Time.
4.10.7 Wetting Time
The method was followed to measure tablet wetting time. A piece of tissue
paper (12 cm X 10.75 cm) folded twice was placed in a small Petri dish (ID = 65 cm)
containing 6 ml of Sorenson’s buffer (pH 6.8), A tablet was put on the paper, and the
time for the complete wetting was measured. Three trials for each batch were
performed and the standard deviation was also determined.

METHODOLOGY
Figure-8: In-vitro Wetting Property.
4.10.8 In-vitro Dispersion Time:
In-vitro dispersion time was measured by dropping a tablet in a glass cylinder
containing 6 ml of Sorenson’s buffer (pH 6.8). Three tablets from each formulation
were randomly selected and in-vitro dispersion time was performed.
Figure-9: In-vitro Disintegration Property.

METHODOLOGY
4.11. CONTENT UNIFORMITY:
Ten randomly selected tablets were weighed and powdered in a glass mortar
pestle. The weight equivalent to 10 mg Ketoprofen was weighed and dissolved in 5
ml of methanol in volumetric flask using magnetic stirrer, the volume was adjusted to
100 ml with Sorenson’s buffer (pH 6.8) and the solution was filtered. An aliquot of
1.0 ml of solution were diluted to 10 ml Sorenson’s buffer (pH 6.8) in separate
volumetric flask. The content in was determined spectrophotometrically at 260 nm.
The results were shown in Table 35.
4.12. IN-VITRO DISSOLUTION STUDIES:
In-vitro dissolution studies of formulation were carried out using USP paddle
method at 50 rpm in 900 ml of Sorenson’s buffer (pH 6.8) as dissolution media,
maintained at 37±0.50C. 5 ml of aliquot was withdrawn at the specified time intervals,
filtered through whatmann filter paper and analysed spectorphotometrically at 260
nm. An equal volume of fresh medium, which was prewarmed at same condition was
replaced into the dissolution media after each sampling to maintain the constant
volume throughout the test.

METHODOLOGY
4.13. STABILITY STUDIES: 105, 106.
Definition:
Stability is defined as “the capacity of the drug product to remain within
specifications established to ensure its identity, strength, quality and purity” (FDA
1987). In other words the stability of a drug is its ability to resist detoriation.
Need for stability studies: Objective and Purpose:
9 It is important that the point of view of the safety of patients, it is important
that the patient receive a uniform dose of a drug throughout the whole of shelf-
life.
9 Consideration must be taken to the relevant legal requirements concerned with
the identity, strength, purity, and quality of the drug.
9 Such a study is important to prevent economic repercussion of marketing an
unstable product.
9 Detoriation of drug may take several forms arising from changes in the
chemical, physical and microbiological properties .These changes may affect
therapeutic value of a dosage form or increases toxicity.
Prediction of shelf-life:
Shelf-life is a period during which a dosage form keeps it qualities. The prediction of
shelf-life is based on applying the Arrhenius equation, which gives the effect of
temperature on rate constant, K of a chemical reaction. The stability of any active
component in a dosage form can be evaluated by determining some properties of the
degradation (such as color disappearance, concentration etc.) Under accelerated
storage conditions as a function of time. If this function is lineared with any of
chemical kinetic orders, temperature dependency of the degradation can be obtained
with the help of Arrhenius equation:

METHODOLOGY
Considering a preparation whose instability is measured in terms of color
disappearance when subjected to different elevated temperatures and a plot is drawn
with absorbance v/s time.
The reaction velocity constant K for the decomposition at each of the elevated
temperature can be calculated from the slope of line. The most satisfactory method for
expressing the influence of temperature on reaction velocity is the quantitative
relation proposed by Arrhenius :
K = A e ‫ ־‬E a / RT
Where :
K = Specific rate constant,
R= Gas constant(1.987cals/day/mol)
T= Absolute temperature,
Ea=Energy of activation.
The Arrhenius equation is then employed to determine the value for decomposition at
room temperature. This is obtained from linear plot of the logarithm of values against
reciprocal of absolute temperature, which is then extrapolated, to room temperature
(250 C). The value of K at 250 C may then substituted in the appropriate rate equation
and an estimate of the time during which the product will maintain the required quantity
or potency (shelf-life).
Most recently a guideline issued by the International Conference on Harmonization
(ICH, 1993) indicates that the purpose of stability testing is to provide evidence on how
the quality of a drug substance or the drug product varies with time under the influence of
vvariety of environmental factors, such as temperature, humidity and light, and enables
recommended storage conditions, retest periods, and shelf life to be established.

METHODOLOGY
The purpose of stability study is not only to characterize the degradation of a drug
product but also to establish an expiration-dating period or shelf life applicable to all
future batches of drug product.
Types of stability studies:
1. The results provide an estimate of the kinetic parameters for the rate of
reactions.
2. The results can be used to characterize the relationship between degradation
and storage condition.
3. The results supply critical information in the design and analysis of long-term
stability studies under ambient conditions at the planning stage.
Long–term studies, which include both pre-approval and post-approval stability
studies, are usually conducted under ambient condition.
A pre-approval stability study is also known as NDA stability study, the purpose
of it is to determine (estimate) a drug expiration dating applicable to all future
batches.
A post approval stability study is usually referred to as a marketing stability study;
the purpose of it is to make sure that the drug product currently on market can meet
the USP/NF specifications up to the end of expiration dating period.
Table-20: Storage cconditions according to ICH guidelines
Study Storage condition Minimum time
Temperature Relative humidity (%)
250C±20C 60% ±5% RH 12 Months

Long term
Intermediate 300± 20C 65%± 5% RH 6 Months
Accelerated 400± 20C 75%± 5% RH 3 Months

METHODOLOGY
Note: The analyst can select any one of the three study conditions. Stability study
was carried out at 400C / 75% RH for the optimized formulations.
The procedure was divided into two parts,
Part I:
Achieving of 60% RH:
26.66 gm. of sodium hydroxide was weighed and dissolved in 100 ml
of distilled water to get 26.66% sodium hydroxide solution. The solution was placed
in the desiccator over which a wire mesh was placed, over which the dosage form was
placed and the desiccator was sealed. The desiccator was placed in the oven
maintained at 250C to create the Relative Humidity OF 60%.
Achieving of 75% RH:
Saturated solution of sodium chloride was prepared and placed in the
desiccators over which a wire mesh was placed, over which the dosage form was
placed and the desiccator was sealed. The desiccator was kept in oven maintained at
400C to create the relative humidity of 75%.
Part II
The sealed formulation were placed in amber colored bottles, tightly plugged with
cotton and capped. They were then stored at 250C /60% RH and 400C / 75% RH for
two months and evaluated for their physical appearance and drug content.
Results are shown in table 45 and 53.

RESULTS
CHAPTER-5.
RESULTS
5.1. Identification Tests:
Physical Appearance:
Physical appearance of drug was examined by various organoleptic properties.
Color : White or almost white;
Odor : Odorless;
Taste : Tasteless;
State : Fine to granular powder.
Melting Point:
Melting point of the Ketoprofen was determined by capillary fusion method;
one sided closed capillary filled with drug and put into the Melting Point Apparatus.
Temperature was noted at which solid drug changed into liquid. It was found to be
950C.
Table-21: Melting point of Ketoprofen.
OBSERVED VALUE
STANDARD
CAPILLARY FUSION DIFFERENTIAL
VALUE
METHOD SCANNING
CALORIMETRY
94-970 C 950 C 94.540 C
DEPT. OF PHARMACEUTICS, Dr.H .L. T. COLLEGE OF PHARMACY Page 123

RESULTS
Infrared Spectral Assignment:
The pellet of approximately 01 mm diameter of the drug was prepared
grinding 3-5 mg of sample with 100-150 mg of Potassium Bromide using hydrostatic
press. The sample pellet was mounted in IR compartment and scanned at wavelength
4000 cm-1 – 500 cm-1. On analysis of the IR spectra of the reference spectra (A) given
in Indian Pharmacopoeia (1996) and pure drug (B), no major differences were
observed in the characteristic absorption peak (1696, 1655) pattern. The results were
shown in Figure 10 (A) and 11 (B).
Figure-10: IR Spectra (A) Ketoprofen IP Spectra
1 1 2 .5
% T
105
9 7 .5
90
8 2 .5
75
6 7 .5
60
5 2 .5
45
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
b a c k g ro u n d 1 /c m
Figure-11: IR Spectra (B) Sample of Ketoprofen

RESULTS
Differential Scanning Calorimetry (DSC):
DSC analysis was performed on 5 mg sample. Samples were heated in an open
aluminum pans at a rate of 100 per min–1 in a 30 to 3000C temperature range under a
nitrogen flow of 40 mL/min. It shows endothermic peak at about 94.120C Figure 12.
Figure-12: Differential Scanning Calorimetry of Ketoprofen
Ultraviolet Absorption Maxima:
Ultraviolet absorption in the rage 200 to 400 nm of a 5μg/ml solution in 5% (v/v)
methanolic Sorenson’s Buffer (pH 6.8) was measured. The absorption maxima (λmax)
of Ketoprofen (5 µg/ml) in this solution was found to be 260 nm which is concordant
with the Indian Pharmacopoeia (1996) shown in Figure 13.

RESULTS
1.4
1.2
1
A b so rb an ce
0.8
0.6
0.4
0.2
0
180 230 280 330 380
Wavelength (nm)
Figure-13: Scan Graph of Ketoprofen
5.2. PREFORMULATION STUDIES
5.2.1. Solubility
The solubility of Ketoprofen was determined in different solvent systems and buffers.
An excess quantity of the drug was mixed with 10 ml of each solvent in screw capped
glass tubes and shaken on constant water bath shaker for 24 hours at 25o. The
solutions were examined physically for the absence or presence of drug particles and
also by spectrophometrically for quantitative determination of drug in buffers. The
results were shown in Table 22.

RESULTS
Table-22: Solubility of Ketoprofen in Different Solvents
S.No. Solvents Solubility
1. Distilled water -
2. Sorenson's buffer pH 6.8 -
3. 0.1 HCl +
4. 0.1 NaOH +
5. Ethanol ++
6. Methanol ++
Practically insoluble (-) slightly soluble (+) soluble (++)
Table-23: Solubility of Ketoprofen in Various Buffer Solutions
S.No Buffers(pH) Solubility(mg/ml)
1. 6.8 (Sorenson's buffer) 0.014±0.002
2. 7.0 (Water) 0.016±0.003
3. 7.4 (Buffer) 0.016±0.002

Data are expressed as mean ± S.D. (n = 3)
5.2.2. Result of calibration curve data
The calibration curve of Ketoprofen was prepared in Sorenson’s buffer (pH
6.8). The plot of different concentrations of Ketoprofen versus absorbance was found
to be linear in the concentration range of 5-25 µg/ml at 260 nm. The absorbances at
different concentrations were shown in Table 24. The data of standard curve were
linearly regressed. The slope and correlation coefficient values were found to be
0.0198 and 0.9979 respectively. The intercept on Y-axis found to be 0.1361. The
calibration curve was shown in Figure 14.

RESULTS
Table-24: Calibration curve data of Ketoprofen
SR.NO. CONCENTRATION ABSORBANCE
1 0 0
2 5 0.211
3 10 0.422
4 15 0.633
5 20 0.837
6 25 1.013
Figure-14: Calibration curve of Ketoprofen

RESULTS
5.2.3. Drug Polymer Interaction Studies:
100
% T
95
90
85
80
75
70
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
c ro o s c a r 1 /c m
Figure-15: IR Spectra of Croscarmallose sodium
100
% T
90
80
70
60
50
40
30
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
c ro o s c a r+ d ru g 1 /c m
Figure-16: IR Spectra of Mixture of Drug and Croscarmallose sodium
9 7 .5
% T
90
8 2 .5
75
6 7 .5
60
5 2 .5
45
3 7 .5
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
ss g 1 /c m
Figure-17: IR Spectra of Sodium Starch Glycolate

RESULTS
9 7 .5
% T
90
8 2 .5
75
6 7 .5
60
5 2 .5
45
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
s s g + d ru g 1 /c m
Figure-18: IR Spectra of Mixture of Drug and Sodium Starch Glycolate
9 7 .5
% T
90
8 2 .5
75
6 7 .5
60
5 2 .5
45
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
coss car 1 /c m
Figure-19: IR Spectra of Crospovidone
100
% T
90
80
70
60
50
40
30
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
d 1/
Figure-20: IR Spectra of Mixture of Drug and Crospovidone

RESULTS
Table-25: Interpretation of drug polymer interaction study.
Characteristics absorption
Code Functional group
peak cm-2
Ketoprofen OH str 3000.50
CH str 2900.01
CHdf 1290.23
C=O str 1650
Ar-H 710
Crospovidone OH str 3200.3
CH str 2980.01
CHdf 1240.23
C=O str 1680.01
Crospovidone+Ketoprofen CH str 3000.01
CHdf 1280.23
C=O str 1700
Ar-H 710
Sodium starch glycolate OH str 3580.01
CH str 2980.01
CHdf 1320.23
C=O str 1600
Sodium starch glycolate+ CH str 3000.01
Ketoprofen CHdf 1280.23
C=O str 1700
Ar-H 710
Crosscarmalose sodium O-H str 3564.85
C-H str 2888.47
C=O str 1616.29
C-O str 997.71
Crosscarmalose sodium + CH str 3000.01
Ketoprofen CHdf 1280.23
C=O str 1700
Ar-H 710

RESULTS
5.3. EVALUATION OF SOLID DISPERSION;
Prepared polymer drug conjugates were evaluated by
1) Determination of solubility of solid dispersion
2) Estimation of drug content
3) In- vitro dissolution studies
4) Dissolution efficiency of solid dispersion
5) FT-IR
6) X-ray diffraction (XRD)
7) Differential scanning calorimeter (DSC)
8) Scanning electron microscopy (SEM)
1. DETERMINATION OF SOLUBILITY OF SOLID DISPERSION:
Table-26: Solubility data of Ketoprofen, physical mixture and solid dispersion in

Sorenson’s buffer pH 6.8 at 25oC and 370C.
FORMULATION
CODE Ketoprofen solubility Ketoprofen solubility
0
(mg/ml) at 25 C (mg/ml) at 370 C
Pure Drug 0.014333 ± 0.003086 0.018417 ± 0.001809
KP1 0.28825 ± 0.002883 0.316167 ± 0.00527
KP2 0.383333 ± 0.002765 0.438917 ± 0.001665
KP3 0.46675 ± 0.003 0.564917 ± 0.002082
KPG1 0.2275 ± 0.002537 0.251833 ± 0.001507
KPG2 0.331 ± 0.002634 0.388333 ± 0.001127
KPG3 0.444917 ± 0.004856 0.501083 ± 0.001127
KPVP1 0.533083 ± 0.002126 0.603833 ± 0.001258
KPVP2 0.6775 ± 0.002537 0.751 ± 0.001146
KPVP3 0.803833 ± 0.003263 0.894417 ± 0.000878
KPEG1 0.481333 ± 0.00366 0.575333 ± 0.001127
KPEG2 0.620167 ± 0.006385 0.715417 ± 0.008098
KPEG3 0.71125 ± 0.005074 0.80475 ± 0.00522

RESULTS
2. ESTIMATION OF DRUG CONTENT:
Table-27: Percent Drug Content of Ketoprofen-PVP K-30 & Ketoprofen-PEG-

6000 Physical Mixtures and Solid Dispersions
SR.NO. Formulation Number %Drug Content
1 KP1 99.08333±0.242813
2 KP2 98.66667±0.438986
3 KP3 98.25±0.450694
4 KPG1 99.025±0.15
5 KPG2 98.10833±0.448144
6 KPG3 98.08333±0.401819
7 KPVP1 99.36667±0.500208
8 KPVP2 98.61667±0.58648
9 KPVP3 98.51667±0.57027
10 KPEG1 98.91667±0.496446
11 KPEG2 97.94167±0.312583
12 KPEG3 98.08333±1.127035

RESULTS
3) IN-VITRO DISSOLUTION STUDIES:
Table-28: Dissolution Release Profile of Ketoprofen from Physical Mixture.
Time Cumulative Mean Percent Drug Release ± Standard Deviation

(min) Pure KP1 KP2 KP3 KPG1 KPG2 KPG3
drug
0 0 0 0 0 0 0 0
5 1.89 5.265 10.2 14.1075 4.38 8.8725 12.03
±0.2025 ±0.2475 ±0.225375 ±0.2475 ±0.213849 ±0.202916 ±0.213849
10 3.7071 12.73335 19.52633 26.19818 12.27487 17.46986 25.08587
±0.259056 ±0.225649 ±0.214098 ±0.214124 ±0.236576 ±0.225225 ±0.236576
15 6.028717 20.18749 26.68052 34.46977 20.531 29.07676 33.82123
±0.236852 ±0.225898 ±0.225862 ±0.237562 ±0.24834 ±0.225475 ±0.236839
30 13.92541 34.4374 42.73013 50.86552 37.80379 43.16403 50.43376
±0.237114 ±0.226148 ±0.226112 ±0.248275 ±0.237114 ±0.248564 ±0.225763
45 24.35837 44.66062 53.42753 62.36694 49.23825 54.54443 61.43971
±0.237376 ±0.237364 ±0.226358 ±0.214898 ±0.214885 ±0.237339 ±0.21486
60 34.2854 52.37515 61.87928 70.82108 54.94037 62.32241 67.83783
±0.226673 ±0.248788 ±0.226609 ±0.237626 ±0.215123 ±0.237601 ±0.20375
Table-29: Dissolution release profile of Ketoprofen from solid dispersion

(min) KPVP1 KPVP2 KPVP3 KPEG1 KPEG2 KPEG3
0 0 0 0 0 0 0
5 7.29 23.2725 36.465 9.93 16.59 25.02
±0.225 ±0.202916 ±0.213849 ±0.236339 ±0.236339 ±0.225
10 18.6156 38.98836 57.04802 23.62853 30.94093 45.3203
±0.22525 ±0.214074 ±0.248077 ±0.248103 ±0.236602 ±0.22525
15 28.70128 54.93165 74.11386 34.62728 43.74029 60.09313
±0.203415 ±0.203379 ±0.236852 ±0.236877 ±0.214373 ±0.203415
30 49.23813 75.73761 90.71859 54.96821 66.06383 78.79731
±0.248564 ±0.172529 ±0.248615 ±0.248641 ±0.214611 ±0.248564
45 61.69028 85.75162 99.81168 68.0492 75.34713 88.3347
±0.214848 ±0.130698 ±0.172872 ±0.237415 ±0.226 ±0.248839
60 70.81119 93.16666 - 74.41716 82.78815 94.59759
±0.226238 ±0.226 ±0.226338 ±0.22625 ±0.249115

RESULTS
Figure-21: Cumulative Percent Release of Ketoprofen from Physical Mixtures of

Ketoprofen-PVP K-30 and Ketoprofen-PEG-6000 Systems
Figure-22: Cumulative Percent Release of Ketoprofen from Solid Dispersions of

Ketoprofen-PVP K-30 and Ketoprofen-PEG-6000 Systems

RESULTS
4. DISSOLUTION EFFICIENCY:
Table-30: Dissolution Efficiency of Ketoprofen-PVP K30 &/ Ketoprofen-PEG

6000 Physical Mixtures and Solid Dispersions.
FORMULATION Dissolution Efficiency (%)

DE 15 DE 30
Pure drug 2.92 6.46
KP1 9.58 18.13
KP2 13.33 23.96
KP3 18.75 30.42
KPG1 8.33 18.95
KPG2 12.91 24.58
KPG3 17.92 29.17
KPVP1 12.91 25.83
KPVP2 30 47.92
KPVP3 44.16 63.33
KPEG1 17.50 31.67
KPEG2 23.33 39.17
KPEG3 34.17 52.08
5. FT-IR STUDY:
97.5
%T
90
82.5
75
67.5
60
52.5
45
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
PVP K30 1/cm
Figure-23: FT-IR Spectra of PVP K 30.

RESULTS
105
%T
97.5
90
82.5
75
67.5
60
52.5
45
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
PVP K30 +KETOPROFEN 1/cm
Figure-24: FT-IR Spectra of Ketoprofen and PVP K 30.
100
%T
90
80
70
60
50
40
30
20
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
PEG-6000 1/cm
Figure-25: FT-IR Spectra of PEG-6000.

RESULTS
100
%T
90
80
70
60
50
40
30
20
10
4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500
PEG-6000+KETOPROFEN 1/cm
Figure-26: FT-IR Spectra of Ketoprofen and PEG-6000.
Table-31: Interpretation of drug polymer interaction study
Code Functional group Charecteristics absorption

peak cm-2
PEG 6000 OH str 3200.50
CH str 2985.01
CHdf 1105.23
PEG 6000+Ketoprofen CH str 2800.01
CHdf 1110.23
C=O str 1700
Ar-H 890
PVP K30 OH str 3550.12
CH str 2980.01
C-N 800.00
C=N str 1650.00
PVP K30+ Ketoprofen CH str 3000.01
CHdf 1280.23
C=O str 1700
Ar-H 710

RESULTS
5. DIFFERENTIAL SCANNING CALORIMETRY ANALYSIS:
Differential Scanning Calorimetry analysis was performed on 5 mg samples.

Samples were heated in an open aluminum pans at a rate of 100 per min–1 in a 30 to
300°C temperature range under a nitrogen flow of 40 mL/min.
Figure-27: DSC of PEG-6000
Figure-28: DSC of PVP K-30

RESULTS
Figure-29: DSC of KPVP-3
Figure-30: DSC of KPEG-3

RESULTS
6. X- Ray Diffraction (XRD)
XRD patterns were recorded using Philips PW 1729 X-ray generator. Powder
X-ray diffraction patterns were traced for Ketoprofen, various carriers and solid
dispersions.
Figure-31: X- Ray Diffraction Ketoprofen
Figure-32: X- Ray Diffraction PVP K-30

RESULTS
Figure-33: X- Ray Diffraction PEG-6000
Figure-34: X- Ray Diffraction KPVP-3

RESULTS
Figure-35: X- Ray Diffraction KPEG-3
7. SCANNING ELECTRON MICROSCOPY:
The external morphology of solid dispersions was analyzed by Scanning

Electron Microscope (SEM). The samples were examined under a scanning electron
microscope JSM 6100 JEOL JAPAN.
Figure-36: Scanning Electron Photomicrograph of Ketoprofen

RESULTS
Figure-37: Scanning Electron Photomicrograph of PVP K-30
Figure-38: Scanning Electron Photomicrograph of Solid Dispersion (KPVP-3)

RESULTS
5.4. Characterization of Blends for Fast Dissolving Tablets:
Table-32: Characterization of Blends.
Formulation Bulk Tapped Hausners Compressibilit Angle

Density density ratio y Index repose
F1 0.681092 0.783293 1.150054 13.04752 23.99959
±0.001094 ±0.001873 ±0.000933 ±0.070577 ±0.520574
F2 0.591251 0.673251 1.13869 12.17977 23.14928
±0.001069 ±0.001386 ±0.000285 ±0.022013 ±0.50656
F3 0.61501 0.704891 1.146146 12.75107 23.2435
±0.002005 ±0.002071 ±0.000411 ±0.031322 ±0.485106
F4 0.670249 0.75873 1.132016 11.66196 23.82844
±0.002695 ±0.002303 ±0.001117 ±0.087151 ±0.837309
F5 0.598567 0.680278 1.13651 12.01126 22.40116
±0.001802 ±0.002444 ±0.001053 ±0.081509 ±0.719261
F6 0.677508 0.755288 1.114806 10.29793 23.7341
±0.000918 ±0.001141 ±0.002766 ±0.222876 ±0.591321
F7 0.567537 0.641849 1.130937 11.57776 23.70906
±0.000644 ±0.000824 ±0.000168 ±0.013142 ±0.491507
F8 0.61535 0.697039 1.132748 11.71899 23.05747
±0.00239 ±0.003689 ±0.001647 ±0.128243 ±0.747942
F9 0.553101 0.630258 1.139499 12.24204 24.26282
±0.001621 ±0.00243 ±0.001186 ±0.091409 ±0.744986
F10 0.608027 0.68151 1.120855 10.78234 23.69731
±0.001129 ±0.00142 ±0.000871 ±0.069326 ±0.999613
F11 0.612746 0.700609 1.143392 12.54091 20.72383
±0.000751 ±0.001501 ±0.001105 ±0.084452 ±0.51672
F12 0.560748 0.656169 1.170168 14.5419 23.11178
±0.000363 ±0.000861 ±0.002224 ±0.16249 ±0.676691
F13 0.608027 0.699304 1.150119 13.05239 25.66395
±0.001129 ±0.001956 ±0.001191 ±0.089995 ±0.45653
F14 0.594061 0.691291 1.163659 14.0602 25.01529
±0.001079 ±0.006953 ±0.009671 2±0.71082 ±0.541887
F15 0.666076 0.75567 1.134509 11.85616 23.78599
±0.001356 ±0.001746 ±0.000311 ±0.024141 ±0.471261
F16 0.585941 0.66756 1.139296 12.22651 23.81718
±0.001727 ±0.001783 ±0.000485 ±0.037362 ±0.730814
F17 0.609016 0.694448 1.140278 12.30212 23.70906
±0.001484 ±0.001929 ±0.00039 ±0.029969 ±0.491507
F18 0.624222 0.722552 1.157521 13.60825 24.3578
±0.001559 ±0.003132 ±0.002128 ±0.158823 ±0.714602
F19 0.657607 0.751127 1.142213 12.45062 23.79845
±0.001 ±0.000652 ±0.000744 ±0.057075 ±0.661456
F20 0.634788 0.741109 1.167491 14.34621 26.10666
±0.001232 ±0.001679 ±0.000379 ±0.027839 ±0.462065

RESULTS
5.5. CHARACTERIZATION OF FAST DISSOLVING TABLETS
Table-33: Characterization of Fast Dissolving Tablets.
Formulation Thickness (mm) Weight (mg) Friability (%) Hardness

(Kg/cm2)
F1 6.325±0.014 500.6667 0.478151 3.166667
±1.527525 ±0.000291 ±0.057735
F2 6.342±0.026 496.6667 0.440411 3.133333
±3.785939 ±0.000269 ±0.057735
F3 6.343±0.034 497.3333 0.639744 2.8
±0.57735 ±0.000256 ±0.1
F4 6.325±0.004 501.3333 0.781955 2.8
±2.081666 ±0.045364 ±0.1
F5 6.349±0.037 496.6667 0.876262 2.733333
±1.527525 ±0.000533 ±0.152753
F6 6.342±0.029 502.6667 0.719904 3
±1.527525 ±0.0006 ±0.173205
F7 6.348±0.043 500.3333 0.519308 3.6
±1.527525 ±0.000432 ±0.1
F8 6.349±0.021 500.3333 0.800108 3
±2.309401 ±0.00103 ±0.173205
F9 6.334±0.034 499.3333 0.638808 3.266667
±1.527525 ±0.00039 ±0.057735
F10 6.325±0.008 498.6667 0.519654 3.533333
±2.081666 ±0.000523 ±0.11547
F11 6.345±0.016 499.3333 0.519792 3.433333
±3.21455 ±0.000208 ±0.11547
F12 6.372±0.031 498.6667 0.719138 3.133333
±0.57735 ±0.000994 ±0.152753
F13 6.346±0.034 501.6667 0.76132 3.166667
±2.081666 ±0.000466 ±0.152753
F14 6.335±0.031 499.3333 0.519662 3.066667
±1.527525 ±0.002573 ±0.208167
F15 6.348±0.031 501.3333 0.478151 3.3
±1.527525 ±0.000396 ±0.2
F16 6.344±0.034 498.6667 0.760102 2.666667
±0.57735 ±0.000978 ±0.152753
F17 6.363±0.035 498.6667 0.67991 2.8
±1.527525 ±0.000415 ±0.173205
F18 6.343±0.016 499.3333 0.840785 2.566667
±2.081666 ±0.000514 ±0.208167
F19 6.366±0.041 498.6667 0.919755 2.5
±3.05505 ±0.000212 ±0.173205
F20 6.321±0.339 500.6667 0.958467 2.7
±1.527525 ±0.000383 ±0.264575

RESULTS
Table-34: Characterization of Fast Dissolving Tablets.
Formulation Disintegration time Wetting time Dispersion time

(Seconds) (Seconds) (Seconds)
F1 95.53333 87.37 114.3467
±1.507459 ±1.770339 ±3.381262
F2 86.50333 80.13667 101.4433
±2.360452 ±3.928897 ±2.408513
F3 70.25667 65.34333 84.76
±3.769726 ±3.674647 ±4.26522
F4 60.65 55.04 71.81
±1.85696 ±3.125972 ±3.404453
F5 51.94667 49.22333 64.70667
±3.34403 ±3.511885 ±4.265024
F6 134.2233 125.6633 142.7133
±5.162183 ±5.760046 ±4.83864
F7 119.93 110.2733 124.9033
±4.994207 ±3.544014 ±4.639874
F8 59.48 80.09333 86.23333
±1.509073 ±4.400231 ±2.717174
F9 45.11333 62.69 69.72333
±2.155327 ±2.507349 ±1.804476
F10 35.60667 48.98333 55.07333
±1.471915 ±3.493799 ±3.127944
F11 47.48333 60.04333 67.46667
±1.878546 ±3.823354 ±2.541679
F12 36.01333 42.94 54.35
±1.651676 ±3.040049 ±2.626385
F13 29.02333 31.83667 42.83667
±1.708489 ±2.848233 ±1.180777
F14 27.71 29.67 33.69667
±1.141753 ±1.477329 ±2.080993
F15 25.68 27.44667 30.91
±1.411063 ±1.404754 ±1.681547
F16 68.31333 59.38333 69.56
±2.26809 ±1.8037 ±1.915385
F17 51.65667 49.47333 56.48
±2.110126 ±2.941451 ±3.137276
F18 39.41 43.66333 49.44667
±2.201704 ±2.033749 ±3.786322
F19 31.52667 36.40667 42.74333
±3.023183 ±1.420047 ±2.555902
F20 29.16 31.11667 34.19
±1.746396 ±2.146214 ±1.93

RESULTS
Figure-39: Effect of Concentration of Superdisintegrant and Effervescent Agent

on Disintegration Time.

on Dispersion Time

on Wetting Time

RESULTS
Table-35: Drug content in the Fast Dissolving Tablets of Ketoprofen
Formulation Drug content Drug content

(mg per tablets) %
F1 49.34167 98.68333
±0.339424 ±0.678847
F2 48.88333 97.76667
±0.440407 ±0.880814
F3 49.46667 98.93333
±0.398696 ±0.797392
F4 48.65833 97.31667
±0.146487 ±0.292973
F5 49.59167 99.18333
±0.177365 ±0.35473
F6 49.06667 98.13333
±0.330088 ±0.660177
F7 49.65 99.3
±0.139194 ±0.278388
F8 49.10833 98.21667
±0.473242 ±0.946485
F9 49.225 98.45
±0.229129 ±0.458258
F10 50.54167 101.0833
±0.052042 ±0.104083
F11 49.24167 98.48333
±0.376109 ±0.752219
F12 49.425 98.85
±0.388104 ±0.776209
F13 49.19167 98.38333
±0.357363 ±0.714726
F14 49.71667 99.43333
±0.177365 ±0.35473
F15 50.36667 100.7333
±0.028868 ±0.057735
F16 48.99167 97.98333
±0.189297 ±0.378594
F17 49.15 98.3
±0.417582 ±0.835165
F18 49.90833 99.81667
±0.23094 ±0.23094
F19 49.025 98.05
±0.238485 ±0.47697
F20 49.06667 98.13333
±0.300347 ±0.600694

RESULTS
5.6. DETERMINATION OF IN-VITRO DRUG RELEASE:
Table-36: Zero Order Dissolution Release Profile of Ketoprofen from F1-F5.

(min) F1 F2 F3 F4 F5
0 0 0 0 0 0
4 38.655 44.565 50.34 54.78 59.655
±0.311769 ±0.340735 ±0.432406 ±0.578619 ±0.343693
8 48.08795 52.32452 60.61093 68.92587 73.49128
±0.289652 ±0.289688 ±0.332174 ±0.579262 ±0.37508
12 55.44633 59.6726 65.38822 73.14238 81.16287
±0.237475 ±0.290009 ±0.350381 ±0.579905 ±0.426119
16 61.08783 68.64878 78.09073 82.0885 86.86288
±0.23774 ±0.290331 ±0.325734 ±0.580548 ±0.358443
20 64.35053 73.31487 83.38228 86.30447 90.55913
±0.238004 ±0.290652 ±0.376293 ±0.327051 ±0.477898

(min) F6 F7 F8 F9 F10
0 0 0 0 0 0
4 27.855 32.085 41.805 54.195 61.035
±0.3245 ±0.38448 ±0.45 ±0.687386 ±0.542494
8 35.29595 41.72065 53.62645 70.93522 77.27282
±0.595313 ±0.306727 ±0.382633 ±0.663655 ±0.496284
12 46.58513 51.66697 67.11098 81.04897 86.1486
±0.375121 ±0.350297 ±0.450425 ±0.451475 ±1.039054
16 52.75682 56.43428 76.66543 84.99387 89.43915
±0.344469 ±0.325651 ±0.687676 ±0.342792 ±0.45225
20 56.4003 61.01183 82.94542 88.26805 91.29325
±0.307538 ±0.474162 ±0.676062 ±0.483679 ±0.45275

RESULTS

(min) F11 F12 F13 F14 F15
0 0 0 0 0 0
4 45.9 50.04 54.345 59.91 63.54
±0.518965 ±0.45 ±0.93675 ±0.687386 ±0.54
8 55.026 59.5456 67.42538 72.12657 82.3456
±0.496258 ±0.474603 ±0.708264 ±0.68815 ±0.473278
12 67.92708 72.3467 76.54523 81.10163 91.69202
±0.680594 ±0.451025 ±0.901775 ±0.4515 ±0.708338
16 73.25243 78.24695 84.32513 87.10158 94.79372
±0.497553 ±0.527136 ±0.452775 ±0.689405 ±0.768666
20 77.60862 85.81867 91.13858 93.8581 99.54875
±0.430121 ±0.938291 ±0.633803 ±0.47544 ±0.45275

(min) F16 F17 F18 F19 F20
0 0 0 0 0 0
4 24.66 45.24 49.785 57.465 63.54
±0.45 ±0.800359 ±0.610962 ±0.518965 ±0.495
8 40.4374 55.28027 63.11532 72.37885 81.1606
±0.4505 ±0.344582 ±0.203281 ±0.590734 ±0.519514
12 57.5973 64.08663 73.71538 77.7692 85.7207
±0.473678 ±0.496918 ±0.473446 ±0.541225 ±0.688499
16 62.56622 68.20772 77.08215 85.28045 90.67577
±0.474203 ±0.497468 ±0.923888 ±0.197644 ±0.956807
20 67.13558 72.6933 81.96757 90.35495 94.75123
±0.519713 ±0.857738 ±0.665137 ±0.78961 ±0.948269

RESULTS
Figure-42: Zero Order Dissolution Release Profile of Ketoprofen from F1-F5

RESULTS
Figure-45: Zero Order Dissolution Release Profile of Ketoprofen from F15-F20.

RESULTS
Table-40: First Order Release Profile of Ketoprofen from F1-F5.
Time Cumulative Mean Percent Drug Retain ± Standard Deviation

(min) F1 F2 F3 F4 F5
0 2 2 2 2 2
4 1.787137 1.743189 1.695663 1.654145 1.605371
±0.001914 ±0.00213 ±0.002499 ±0.00437 ±0.002529
8 1.714759 1.67774 1.594699 1.490651 1.422364
±0.001901 ±0.00207 ±0.002774 ±0.00638 ±0.004533
12 1.649755 1.604942 1.538543 1.427029 1.273178
±0.0022 ±0.002451 ±0.003193 ±0.007398 ±0.007435
16 1.591083 1.495403 1.339686 1.250001 1.116111
±0.002522 ±0.003159 ±0.00462 ±0.011149 ±0.00914
20 1.553143 1.425265 1.218891 1.135015 0.970332
±0.002756 ±0.003718 ±0.007276 ±0.007452 ±0.017108

(min) F6 F7 F8 F9 F10
0 2 2 2 2 2
4 1.857931 1.831815 1.764873 1.660154 1.590298
±0.001392 ±0.001555 ±0.001943 ±0.004465 ±0.003815
8 1.804592 1.765118 1.664228 1.462246 1.356155
±0.00375 ±0.001707 ±0.003353 ±0.00674 ±0.005771
12 1.727155 1.683761 1.517007 1.277506 1.134667
±0.002247 ±0.002283 ±0.003449 ±0.006014 ±0.025065
16 1.673972 1.638683 1.373464 1.181646 1.02329
±0.002167 ±0.002316 ±0.008384 ±0.010476 ±0.01087
20 1.638938 1.590815 1.22344 1.07293 0.939256
±0.002293 ±0.003136 ±0.012335 ±0.014005 ±0.013235

RESULTS

(min) F11 F12 F13 F14 F15
0 2 2 2 2 2
4 1.732997 1.698605 1.657974 1.602161 1.561769
±0.002577 ±0.002264 ±0.006589 ±0.005106 ±0.003728
8 1.65279 1.606694 1.511876 1.443891 1.246512
±0.002906 ±0.003174 ±0.006355 ±0.007373 ±0.006938
12 1.506651 1.441689 1.369905 1.276296 0.921493
±0.004857 ±0.004107 ±0.009743 ±0.006031 ±0.018891
16 1.426966 1.331485 1.195016 1.107392 0.71432
±0.00491 ±0.009831 ±0.007304 ±0.016137 ±0.036197
20 1.350146 1.14619 0.941629 0.786447 #NUM!
±0.004714 ±0.021633 ±0.023239 ±0.020371 ±#NUM!

(min) F16 F17 F18 F19 F20
0 2 2 2 2 2
4 1.877018 1.739072 1.701126 1.628484 1.561777
±0.0015 ±0.003194 ±0.002799 ±0.00328 ±0.003416
8 1.774961 1.650852 1.56808 1.441851 1.274383
±0.0019 ±0.001673 ±0.001913 ±0.00483 ±0.007451
12 1.62729 1.555035 1.41951 1.346827 1.151927
±0.002878 ±0.003646 ±0.004647 ±0.006143 ±0.014526
16 1.573142 1.502065 1.359681 1.169857 0.960707
±0.003265 ±0.004125 ±0.010346 ±0.00314 ±0.033532
20 1.516572 1.435818 1.25414 0.983189 0.711549
±0.004071 ±0.00816 ±0.010936 ±0.02068 ±0.049413

RESULTS
Figure-46: First Order Release Profile of Ketoprofen from F1-F5

RESULTS

RESULTS
Table-44: Fit of various kinetics Models for fast dissolving Tablets of Ketoprofen
Formulatio Zero order First order

Code Intercept R2 Slope K Intercept R2 Slope K t1/2
-1
(mg/min) (min )
F1
16.29 0.797 2.831 6.519793 1.922 0.9 0.02 0.04606 15.04559
F2
17.88 0.808 3.187 7.339661 1.921 0.935 0.026 0.059878 11.57353
F3
20.23 0.806 3.606 8.304618 1.923 0.955 0.035 0.080605 8.597482
F4
23.89 0.757 3.697 8.514191 1.892 0.944 0.04 0.09212 7.522796
F5
26.56 0.734 3.872 8.917216 1.881 0.956 0.048 0.110544 6.268997
F6
10.19 0.891 2.628 6.052284 1.957 0.952 0.017 0.039151 17.7007
F7
12.76 0.856 2.771 6.381613 1.945 0.938 0.019 0.043757 15.83747
F8
15.63 0.883 3.805 8.762915 1.962 0.99 0.037 0.085211 8.132753
F9
24.39 0.76 3.884 8.944852 1.889 0.946 0.044 0.101332 6.838906
F10
28.2 0.711 3.932 9.055396 1.856 0.93 0.051 0.117453 5.900232
F11
18.78 0.812 3.45 7.94535 1.919 0.946 0.03 0.06909 10.0304
F12
20.05 0.821 3.76 8.65928 1.932 0.974 0.039 0.089817 7.715689
F13
22.67 0.8 3.962 9.124486 1.933 0.978 0.048 0.110544 6.268997
F14
25.69 0.761 3.998 9.207394 1.92 0.973 0.055 0.126665 5.471125
F15
29.06 0.761 4.291 9.882173 1.993 0.972 0.091 0.209573 3.306724
F16
8.74 0.924 3.332 7.673596 1.976 0.974 0.024 0.055272 12.53799
F17
19.4 0.774 3.151 7.256753 1.906 0.907 0.025 0.057575 12.03647
F18
21.73 0.776 3.588 8.263164 1.9 0.936 0.035 0.080605 8.597482
F19
25.26 0.752 3.861 8.891883 1.896 0.961 0.046 0.105938 6.541562
F20
29.32 0.704 3.998 9.207394 1.874 0.962 0.059 0.135877 5.100201

RESULTS
5.7. STABILITY STUDY:

Table-45: Effect of Storage Condition (40°C/75%RH) on Weight of the
Ketoprofen Tablets.
FORMULATION PERIOD Weight (mg/tablet)

Initial 501.3333±2.081666
st
F4 1 month 501±1
2nd month 500.6667±1.154701
3rd month 499.6667±0.57735
Initial 498.6667±2.081666
F10 1st month 497.6667±0.57735
2nd month 497±1
rd
3 month 496.6667±0.57735
Initial 501.3333±1.527525
F15 1st month 500.6667±0.57735
nd
2 month 500.3333±0.57735
3rd month 499.3333±1.154701
Initial 499.3333±2.081666
F18 1st month 499.3333±0.57735
nd
2 month 499±1
rd
3 month 498.3333±1.527525
Table-46: Effect of Storage Condition (40°C/75%RH) on Hardness of the
Ketoprofen Tablets
FORMULATION PERIOD HARDNESS (Kg/cm2)

Initial 2.8±0.1
st
F4 1 month 2.766667±0.057735
2nd month 2.733333±0.057735
rd
3 month 2.633333±0.057735
Initial 3.533333±0.11547
st
F10 1 month 3.5±0.1
nd
2 month 3.466667±0.057735
3rd month 3.4±0.1
Initial 3.3±0.2
F15 1st month 3.233333±0.057735
2nd month 3.133333±0.11547
rd
3 month 3.1±0.1
Initial 2.566667±0.208167
F18 1st month 2.533333±0.057735
2nd month 2.5±0.1
rd
3 month 2.466667±0.057735

RESULTS
Table-47: Effect of Storage Condition (40°C/75%RH) on Friability of the
Ketoprofen Tablets
FORMULATION PERIOD FRIABILITY (%)

Initial 0.781955±0.045364
F4 1st month 0.770353±0.022919
nd
2 month 0.770454±0.02283
3rd month 0.770353±0.022919
Initial 0.519654±0.000523
st
F10 1 month 0.505719±0.022938
2nd month 0.492471±0.022763
rd
3 month 0.479425±0.000383
Initial 0.478151±0.000396
F15 1st month 0.478723±0.00022
2nd month 0.465539±0.022727
3rd month 0.452306±0.02299
Initial 0.840785±0.000514
F18 1st month 0.840448±0.000194
nd
2 month 0.827441±0.02321
3rd month 0.814198±0.046149
Table-48: Effect of Storage Condition (40°C/75%RH) on Disintegration Time of
FORMULATION PERIOD Disintegration time (Sec.)

Initial 60.65±1.85696
st
F4 1 month 59.96667±1.028462
2nd month 57.41333±0.276827
rd
3 month 56.25±1.166576
Initial 35.60667±4.400231
F10 1st month 35.07±0.343948
2nd month 33.91±0.765441
rd
3 month 31.84±1.557337
Initial 25.68±1.404754
F15 1st month 24.96667±0.341516
2nd month 23.19±0.629603
3rd month 21.91667±0.658584
Initial 39.41±2.033749
F18 1st month 38.52±0.52915
nd
2 month 36.51667±0.835244
rd
3 month 34.16667±0.501631

RESULTS
Table-49: Effect of Storage Condition (40°C/75%RH) on Drug Content of the
Ketoprofen Tablets
FORMULATION PERIOD DRUG CONTENT (%)

Initial 97.31667±0.146487
F4 1st month 96.8±0.163936
nd
2 month 96.35±0.222205
3rd month 95.68333±0.076376
Initial 101.0833±0.052042
st
F10 1 month 100.2333±0.112731
2nd month 99.6±0.163936
rd
3 month 99.06667±0.052042
Initial 100.7333±0.028868
F15 1st month 100.3167±0.152753
2nd month 99.86667±0.062915
rd
3 month 99.08333±0.112731
Initial 99.81667±0.11547
F18 1st month 99.43333±0.146487
2nd month 98.71667±0.101036
3rd month 97.81667±0.062915
Table-50: In-vitro release profile of F4 during Stability studies at (40°C/75%RH)
Time Cumulative % drug release (X± S.D)*

(min) Initial 1month 2 month 3 month
0 0 0 0 0
4 54.78 54.225 53.28 48.57
±0.578619 ±0.16225 ±0.862076 ±0.706275
8 68.92587 68.41525 67.1842 60.98397
±0.579262 ±0.09005 ±1.024416 ±0.40575
12 73.14238 72.7512 72.1487 68.23667
±0.579905 ±0.315977 8±0.31787 ±0.563844
16 82.0885 81.45688 80.7338 76.99735
±0.580548 ±0.203206 ±0.348173 ±0.434243
20 86.30447 85.79215 84.60327 80.66768
±0.327051 ±0.248372 ±0.213942 ±0.40811

RESULTS
Table-51: In-vitro release profile of F10 during Stability studies at

(40°C/75%RH)

0 0 0 0 0
4 61.035 60.285 56.715 53.595
±0.542494 ±0.226495 ±0.274955 ±0.18
8 77.27282 76.43198 74.73302 72.17955
±0.496284 ±0.324749 ±0.248143 ±0.34389
12 86.1486 85.08183 83.90598 80.47968
±1.039054 ±0.231533 ±0.338327 ±0.300171
16 89.43915 88.7912 87.92905 84.57395
±0.45225 ±0.182528 ±0.33263 ±0.338649
20 91.29325 90.52458 89.42148 87.38267
±0.45275 ±0.274748 ±0.22781 ±0.473953

(40°C/75%RH)

0 0
0 0 0
4 63.54 63.36 62.505 60.315
±0.54 ±0.623538 ±0.433964 ±0.226495
8 82.3456 82.1654 81.26445 79.71702
±0.473278 ±0.574036 ±0.468855 ±0.206467
12 91.69202 91.34662 90.23467 88.07052
±0.708338 ±0.848396 ±0.522542 ±0.406302
16 94.79372 94.35793 92.83975 90.4032
±0.768666 ±1.04017 ±0.644826 ±0.341573
20 99.54875 99.20248 98.83762 96.93837
±0.45275 ±0.751317 ±0.314367 ±0.543773

RESULTS

(40°C/75%RH)

0 0
0 0 0
4 49.785 49.47 47.955 47.685
±0.610962 ±0.774645 ±0.655725 ±0.230922
8 63.11532 62.82997 62.03328 61.50798
±0.203281 ±0.3252 ±0.350264 ±0.2263
12 73.71538 73.54972 72.81215 72.37627
±0.473446 ±0.560165 ±0.230413 ±0.612642
16 77.08215 76.6313 75.08292 74.27155
±0.923888 ±1.217887 ±0.43459 ±0.868621
20 81.96757 81.38122 80.53612 79.46885
±0.665137 ±0.317976 ±0.48254 ±0.852313
Figure-50: In-vitro release profile of F4 during Stability studies at
(40°C/75%RH)

RESULTS
(40°C/75%RH)
(40°C/75%RH)

RESULTS
(40°C/75% RH)
Stability studies were conducted for the formulations F4, F10, F15 and F18.
The reasons for selection is, these four formulation have shown best results in term of
weight, hardness, friability, in-vitro disintegration, drug content, in-vitro drug release
studies. Stability studies of the prepared fast dissolving tablets were performed at
different temperatures (400C/75RH). The tablets were analyzed for weight, hardness,
friability, in-vitro disintegration time, and for drug content in each formulation at a
time interval of one month for the period of three months.
All the formulations showed no significant variation in all the parameters
under the test period conditions.

DISCUSSION
CHAPTER-6.
DISCUSSION
In the present project FDT of Ketoprofen were prepared and evaluated for
achievement of fast action of active moiety. The tablets were prepared by direct
compression method by using solid dispersion technology. Fast disintegration of
tablets was achieved by using superdisintegrants and effervescent agents. The
Ketoprofen is water insoluble drug so this is necessary to increase the water solubility
of the drug for that purpose firstly the solid dispersion of Ketoprofen were prepared
with PVP K-30 and PEG-6000 and evaluated. The optimized solid dispersion was
incorporated in FDTs. These prepared tablets were evaluated for there quality control
parameter.
The gift sample of Ketoprofen was analyzed by various organoleptic,
physicochemical and spectrophotometric methods. The sample of Ketoprofen
possesses similar color, odor, taste and texture as given in officials. The melting point
of procured sample was analyzed by capillary fusion method and found 950 C. The
FT-IR spectrum of drug sample was concordant with reference spectra as given in IP
1996. The IR spectra of reference and sample are shown in Figure 10 (A) and 11 (B)
respectively. The FT-IR spectra verified the authenticity of the procured sample,
characteristics peak of Ketoprofen are present at 1700 cm-1 and 1650 cm-1 in sample
spectra. The absorption maxima of Ketoprofen was observed at 260 nm in 5%
methanolic Sorenson’s buffer, which is concordant with the value given in IP 1996.
The UV spectra of Ketoprofen were shown in Figure 13. The DSC of drug sample

DISCUSSION
shows a sharp endothermic peak at 94.540C, which further support the authenticity of
the procure sample.
The qualitative solubility of Ketoprofen was determined in various solvent
systems. The maximum solubility was found in methanol and ethanol and least in
distilled water. The solubility of Ketoprofen was shown in Table 22. Solubility of
Ketoprofen was also determined quantitatively in different buffers (pH), results were
shown in Table 23. The calibration curve of Ketoprofen was prepared in Sorenson’s
buffer (pH 6.8). The plot of different concentrations of Ketoprofen versus absorbance
was found linear in the concentration range of 0-25 μg/ml at 260 nm. The absorbances
at different concentrations were shown in Table 24. The data of standard curve was
linearly regressed. The slope and correlation coefficient values were found 0.0409 and
0.9991 respectively. The intercept on Y-axis found 0.0083. The calibration curve was
shown in Figure 14.
Drug-polymer interaction study was carried out and evaluated for physical
changes, change in absorption maxima and by FT-IR studies. Results were shown in
Figure 15-20. There was not any sign of physical change and change in absorption
maxima at the end of study. The FT-IR spectra of the various physical mixtures retain
all the peaks of the pure drug. So there was no significant shift in the peaks
corresponding to the drug were observed on storage. Both the drug and polymers were
compatible with each other. Hence the drug and polymers can be successfully
incorporated in the design of solid dispersion as well as fast dissolving tablets.
Physical mixtures and solid dispersions of Ketoprofen with PVP K-30& solid
dispersions of Ketoprofen with PEG-6000 (1:1 to 1:3) were prepared by solvent
evaporation technique, the prepared PM and SD were evaluated for drug content,

DISCUSSION
solubility, FT-IR, XRD, DSC and SEM. The composition of various formulations of
physical mixtures and solid dispersion were shown in Table 8-12.
The drug content of physical mixtures (KP1-KP3 & KPG1-KPG3) and solid
dispersions (KPVP1-KPVP3 & KPEG1-KPEG3) was found to be from 97.94 to
99.37, which is found to be within the range of ±1 % of the theoretical claim (Table
27), which shows the uniformity and reproducibility of the obtained method. The
saturation solubility of pure drug, PM and SD was found to be 0.014mg/ml,
0.228mg/ml to 0.711mg/ml and 0.252 mg/ml to 0.894 mg/ml. The results were shown
in Table 26.
It was observed that the saturation solubility of drug was increased by 20 to 50
folds by converting the drug into solid dispersion, due to change in physical state of
Ketoprofen from crystalline to amorphous state which was confirmed by the IR,
XRD, DSC and SEM studies.
The comparison of FT-IR of the physical mixture of PVP K30 and drug &/
PEG-6000 and drug with the FT-IR of its individual components was done to observe
any interactions between drug and polymer. The FT-IR spectra of Ketoprofen, PVP
K30, PEG-6000, and the corresponding physical mixture are shown in Figure 11 (B)
and 23-26. The FT-IR of various mixtures revel all the peaks of the drug. As it can be
seen, a strong absorption peaks at 1696 and 1655 cm−1 occurs in the IR spectrum of
Ketoprofen. So there is no significant shift in the peak corresponding to the drug or
the polymer was observed in the physical mixtures and solid dispersions. The results
clears that there is no chemical interaction in with the chemical entity of Ketoprofen,
only the physical entrapment is observed which is further evaluated by DSC and SEM
studies.

DISCUSSION
The DSC runs for Ketoprofen, PVP K30, PEG-600 and solid dispersions
(KPVP3, KPEG3) are shown in Figure 27-30. The DSC curve for Ketoprofen showed
a sharp melting endotherm at 94.540C. The DSC curve for PEG-6000 showed a sharp
melting endotherm at 63.270C The DSC curve for PVP K30 showed glass transition
peaks at 178.140C. The Solid dispersions KPVP3 & KPEG3 showed no shift in the
melting endotherm for Ketoprofen indicating that there is no chemical interaction
between the Ketoprofen and PVP K30 &/ PEG-6000 in the solid dispersions. All the
solid dispersion exhibited no endothermic peak corresponding to the melting of
Ketoprofen indicating that the drug is dispersed amorphously in the PVP K30 and
PEG-6000 matrix.
The X-ray diffraction patterns for pure Ketoprofen, PVP K 30, PEG-6000 and
solid dispersions (KPVP3, KPEG3) are depicted in Figure 31-35. The pure drug
showed numerous sharp peaks demonstrating the crystalline nature of the drug
whereas, Polyvinylpyrolidone K 30 showed diffused peaks indicating the amorphous
nature of the polymer and PEG-6000 also showed diffused peak. Ketoprofen showed
characteristic intense peaks between the 2θ of 6.5o and 23o due to its crystalline
nature. Whereas, in case of solid dispersions, no intense peaks related to drug were
noticed between the 2θ of 6.5o and 23o. All the SD granules showed diffused peaks
indicating that the drug is dispersed at the molecular level in the polymer matrix and
hence, no crystals were found in the solid dispersion.
The SEM of pure Ketoprofen, pure PVP K30 are shown in Figure 36 and 37
respectively. It was seen that Ketoprofen is highly crystalline material. PVPK30 was
present in globular form. It was found that the crystals of Ketoprofen were dispersed
between the carriers in the KPVP3 formulations as shown in Figure 38. The change in

DISCUSSION
crystalline nature of Ketoprofen in solid dispersion can be easily seen in SEM, which
revels that the drug is completely dispersed in polymeric matrix. The SEM also
supports data obtained from IR, XRD and DSC.
The in-vitro release profile of Ketoprofen of PVP K30 physical mixtures,
Ketoprofen of PEG-6000 physical mixture, and solid dispersions formulations KP1,
KP2, KP3, KPG1, KPG2, KPG3, KPVP1, KPVP2, KPVP3, KPEG1, KPEG2 and
KPEG3 are shown in Table 26-27 and the graph for the comparison of the cumulative
percent release is illustrated in Figure 21-22. In all the cases, cumulative percent
release was much greater than pure Ketoprofen. It is apparent from the Table and the
Figure that as the percent of carrier (PVP K30 & PEG-6000) is increased the
dissolution rate is increased. Pure Ketoprofen yield the low release due to its
hydrophobic property causing the powder to float on the surface of the dissolution
media and prevented its surface to make contact with medium for initial time
intervals.
The percentage drug dissolved from the solid dispersions of Ketoprofen-PVP
K30 & Ketoprofen-PEG-6000 was compared with that dissolved from an equal
amount of physical mixtures and pure crystalline Ketoprofen. In all cases, increasing
the proportion of carrier resulted in the enhancement of the dissolution rate. This
extent of enhancement was markedly greater for the solid dispersions in comparison
with the pure drug and physical mixtures.
Several mechanisms may be possible for the enhanced release of Ketoprofen
in the solid dispersion formulation with the water soluble polymer PVP K30 and PEG
6000. The reduction of crystallinity of drug resulting in improved release (supported
by X-ray diffraction and SEM studies).

DISCUSSION
This suggests that a uniform distribution of drug in the polymer crust at
molecular level in a highly dispersed state. Thus, when such system comes in contact
with an aqueous dissolution medium, the hydrophilic carrier dissolves and results in
precipitation of the embedded drug into fine particles, which increases the dissolution
surface available. Moreover, other factors such as absence of aggregation and/or re-
agglomeration phenomenon during dissolution and particle size reduction may be
attributed to better dissolution profile.
The enhancement of dissolution of Ketoprofen from solid dispersions may be
due to the amorphous nature of the drug in solid dispersions.
Dissolution efficiency of pure Ketoprofen and all the physical mixtures and
solid dispersion formulations at 15 minutes and 30 minutes were calculated which is
shown in Tables 30. As the dissolution time was increased from 15 to 30 minutes, the
dissolution efficiency was increased in all the formulations. Among the formulations
KPVP3 has shown maximum dissolution efficiencies of 44.16% and 63.33% at fifteen
minutes (DE15) and thirty minutes (DE30) respectively. However, KP1, KP2, KP3,
KPG1, KPG2, KPG3, KPVP1, KPVP2, KPEG1, KPEG2 and KPEG3 also produce
comparable results on terms of dissolution efficiency.
From the above characterization of solid dispersions the KPVP3 (solid
dispersion of Ketoprofen with PVP K30 in ratio 1:3) found to be more approachable
for incorporation in fast dissolving tablets.
In the present study, total twenty drug formulations were formulated using
KPVP3 (1:3 ratio Solid dispersion). Ingredients for prepared tablets are shown in
Table 13-16. The formulated blends and prepared tablets were examined for their
physical properties.
DISCUSSION
The characterization of mixed blend was done for determination of mass
volume relationship parameters. The evaluated parameters are bulk density, tapped
density, Hausners ratio, Compressibility index, angle of repose.
The bulk density of mixed blend varied between 0.553 to 0.681 gm/cm3. The
results indicating good packaging capacity of tablets. The tapped density was found in
the range of 0.630 to 0.783 gm/cm3. By using these two density data Hausners Ratio
and compressibility index was calculated. If the bed particle is more compressible
then the powder will be less flowable and vice versa. Material having value less than
16% termed as free flow materials. The powder blends of all formulation had
Hausners ratio of 1.2 or less indicating the good flowablity. The compressibility index
was found between 10.782 to 14.542 %. The compressibility-flowability correlation
data indicating a good flowability of the powder blend.
The flowability of the powder was also evidenced by the angle of repose. The
angle of repose is below than 30o range good to excellent flow properties of powder.
Lower the friction occurring within the mass and the better flow rate. The angle of
repose was found to be 20.72-26.11o. The results for characterization of blend were
shown in Table 32. This indicates the good flow property of the formulated mixed
blend due to the addition of talc as lubricant and magnesium stearate as glidant in the
2% w/w and 2% w/w of the tablet weight respectively.
After compression of powder, the tablets were evaluated for their organoleptic
(Color, Odour, Taste), physical (Size, Shape and Texture) and quality control
parameters (Diameter, Thickness, Hardness, Friability, Disintegration Time and
Wetting Time). All the formulations were white in color, odorless, flat in shape with
smooth surface not having any defects.

DISCUSSION
The thickness of the tablet was found 6.321-6.372 mm. The average weight of
the prepared tablet was found 496.67-502.67 mg. So it was predicted that all the
tablets exhibited uniform weight with low standard deviation values within the
acceptable variation as per IP. The results are shown in Table 33. The friability of all
the formulations was found to be less than 1.0 %, which indicates the tablet’s ability
to withstand abrasion in handling, packaging and shipment. The hardness of tablet
was varied from 2.5-3.6 kg/cm2, which has satisfactory strength to withstand with the
applied mechanical shocks. Friability of F5, F19 and F20 are found very near to one
so these formulations are not forwarded for further studies.
A disintegrant was incorporated in all the formulations to facilitate a breakup
or disintegration of the tablet when it contacts with water or saliva in mouth.
Disintegrants drawing the water into the tablet causes swelling and burst apart. In the
formulation of fast dissolving tablet the three superdisintegrants (croscarmallose
sodium, Sodium Starch Glycolate and Crospovidone) and effervescent agent (Citric
acid and Sodium bicarbonate) were used in different concentrations. The tablets with
Crospovidone disintegrate faster then the tablets with the Citric acid, Sodium Starch
Glycolate and croscarmalose sodium. The tablets prepared with effervescent
technology elaborates the carbon di oxide gas when the tablet comes in contact with
little amount of saliva or water due to reaction between citric acid and sodium
bicarbonate which results in breakup of tablets. The disintegration time of all the
formulations were found between 25.68±1.41 sec to134.22±5.16 Sec. The results
were shown in Table 34. The disintegration process of the tablet was fully dependable
on nature and concentration of used superdisintegrant. The in-vitro wetting time was
also studied to know the time required for complete wetting of tablets when placed on
tongue. The in-vitro wetting time of all the formulations were varied between

DISCUSSION
27.45±1.40 to 125.66±5.76. The results were shown in Table 34. The swelling
properties of the superdisintegrant were depend upon their concentration and the
results shows that as the concentration of the superdisintegrant increased the time
taken for swallowing was reduced. The swelling time was rapid in Crospovidone
followed by citric acid, croscarmalose sodium and Sodium starch glycolate. The same
sequence was observed in case of measurement of dispersion time of the tablet. The
results were tabulated in 34.
The drug content of all the tablet formulations was determined
spectrophotometrically at 260 nm. It varied from 48.65833 ±0.146487 to 50.54167
±0.052042 mg per tablet. The correlation of variation was found to be less than 0.5,
indicating uniformity of the drug content in the prepared tablets. The results of the
content uniformity and percent drug content were shown in Table 35.
In-vitro drug release experiments were performed at 37±1oC in eight basket
dissolution apparatus. The results of dissolution profile are shown in Table 36-39 and
Figure 42-45. The maximum drug release was found in formulation F15 (99.56%).
The order of drug release was found to be:
F15>F20>F14>F10>F13>F5>F19>F9>F4>F12>F3>F8>F18>F11>F2>F17>F16>
F7>F1>F6
Formulations F5, F10, F15 and F20 which contains 5% of Croscarmallose
sodium, Sodium starch glycolate, Crospovidone and citric acid + sodium bicarbonate
respectively. The release was estimated after twenty minutes was 90.559%, 91.293%,
99.548% and 94.751% respectively. The formulation with Crospovidone shows more
release than the tablets with Citric acid, Croscarmallose sodium and Sodium starch
glycolate.

DISCUSSION
The experiment proves that the disintegration is also a release rate-limiting
step for the drug release. The disintegrant Crospovidone shows the faster
disintegration than other. So release of drug and release rate was higher from these
tablets. From the observed data, it can be clear that less time in disintegration enhance
the release rate of Ketoprofen from Fast Dissolving Tablet
Next the release data obtained were subjected for the kinetic treatment to
know the type and order of drug release.
The obtained data from in-vitro Drug release study are tabulated and
represented graphically as:
(a) Cumulative percentage drug release v/s Time (Zero order release
kinetics)
(b) Log cumulative percentage drug retained v/s Time (First order release
kinetics)
The zero order kinetics models data are shown in Table 36-39, and graphically
as Figure in 42-45.
The first order kinetics model data are shown in Table 40-43, and graphically
as Figure 46-49.
For the in-vitro drug release profile it is evident that the kinetics of drug
release is first order for all the prepared fast dissolving tablets as the plot between Log
cumulative percent drug retained versus Time showed the good linearity of ‘R2’
obtained was near to one. The prepared final preparation gives better in terms of
release profile.

DISCUSSION
Formulations which show maximum drug release from each disintegrants and
also having friability less than 0.9 % were selected for the stability studies. These
include F4, F10, F15 and F18.
Stability studies of the prepared fast dissolving tablets were performed at
temperatures (400C/75RH). The tablets were analyzed for weight, hardness, friability,
in-vitro disintegration time, and for drug content in each formulation at a time interval
of one month for the period of three months.
All the formulations showed no significant variation in all the parameters
under the test period conditions.

CONCLUSION
CHAPTER-7.
CONCLUSION
The data obtained from the study of “Formulation and evaluation of
fast dissolving tablets of Ketoprofen” reveals following conclusion:
For improved the solubility of Ketoprofen solid dispersion was prepared by
using PVP K30 and PEG 6000 in different drug: polymer ratio (1:1 to 1:3) by
solvent evaporation method.
Solid dispersions were evaluated for solubility, percent drug content,
dissolution efficiency, in-vitro drug release studies and drug polymer
interaction studied by FT-IR, DSC, XRD, and surface morphology by SEM,.
Formulations containing Ketoprofen-PVP K30 solid dispersions in 1:3 ratio
(KPVP3) showed better dissolution rate, dissolution efficiency. And on the
basis of in-vitro release formulation (KPVP3) was chosen for FDT.
Fast dissolving tablets were prepared by adding different concentrations
(1-5%) of superdisintegrants and by effervescent technology.
The characterization of mixed blend was carried out for all formulation.
The bulk density of mixed blend varied between 0.553±0.001621 to 0.681
±0.001094 gm/cm3.
The tapped density was found in the range of 0.630 ±0.00243 to 0.783
±0.001873 gm/cm3.
The powder blends of all formulation had Hausners ratio less than 1.2
indicating the good flowablity.
The compressibility index was found between 10.298±0.222876 to 14.542
±0.16249%.

CONCLUSION
The angle of repose was found between 20.72±0.51672 to 26.11o±0.462065.
The tablets were prepared & characterized.
The weight of the tablets of all formulation was found to be 496.67±1.527525
to 502.6667±1.527525 mg.
The friability of all formulation was found to be 0.440411±0.000269 to
0.958467±0.000383%.
The hardness of all formulation was found to be 2.5±0.173205 to 3.6±0.1
kg/cm2.
The disintegration time of all the formulations were found between
25.68±1.41 to134.22±5.16 secs.
The in-vitro wetting time of all the formulations were varied between
27.45±1.40 to 125.66±5.76 secs.
The dispersion time of all formulation were varied between 30.91±1.681547 to
142.7133±4.83864 secs.
Drug content of all formulation varied from 48.65833 ±0.146487 to 50.54167
±0.052042 mg per tablet.
The order of drug release was found to be: F15>F20>F14>F10>F13>F5>
F19>F9>F4>F12>F3>F8>F18>F11>F2>F17>F16>F7>F1>F6
Formulations F5, F10, F15 and F20 which contains 5% of Croscarmallose
sodium, Sodium starch glycolate, Crospovidone and citric acid + sodium
bicarbonate respectively. The release was estimated after twenty minutes was
90.559%, 91.293%, 99.548% and 94.751% respectively. The formulation with
Crospovidone shows more release than the tablets with Citric acid + Sodium
bicarbonate, Croscarmallose sodium and Sodium starch glycolate.

CONCLUSION
Stability study for F4, F10, F15 and F18 were performed at temperatures
(400C/75%RH). All the formulations showed no significant variation in all the
parameters evaluated under the test period condition.
From the above studies it was concluded that the F15 is best formulation for
Fast Dissolving Tablets of Ketoprofen.

SUMMARY
CHAPTER-8.
SUMMARY
Compounds with poor aqueous solubility are extremely challenging to be
developed as new formulations. It is well known that drug dissolution rather than
permeation through the epithelia of the gastrointestinal tract is responsible for a low oral
absorption. One of the pharmaceutical strategies to improve the oral bioavailability that
is solid dispersions. Ketoprofen was selected a model drug for the research work because
it has a poor aqueous solubility and low dissolution rate, while high permeability.
The Ketoprofen was formulated as physical mixture and solid dispersions with
PVP K30 & PEG-6000 in different ratios in order to improve the drug dissolution.
Ketoprofen-PVP K30 solid dispersions & Ketoprofen- PEG-6000 solid dispersions were
prepared by solvent evaporation technique.
Solid dispersions were evaluated for solubility, percent drug content, dissolution
efficiency (DE15 and DE30), in-vitro drug release studies and characterized by FT-IR,
DSC, XRD, SEM.
Formulations containing Ketoprofen-PVP K30 solid dispersions in 1:3 ratio
(KPVP3) prepared by solvent evaporation technique showed better dissolution rate and
dissolution efficiency. And on the basis of in-vitro drug release study formulation
(KPVP3) was selected for preparation of FDT.
Fast dissolving tablets were prepared
• by adding different concentrations (1-5%) of superdisintegrants
• by effervescent technology
The disintegration properties of tablet were observed as Crospovidone > Citric
acid + Sodium bicarbonate >Sodium starch glycolate > Ac-Di-Sol. The rapid drug
DEPT. OF PHARMACEUTICS, Dr.. H. L. T. COLLEGE OF PHARMACY. Page 180

SUMMARY
dissolution might be due to the easy and fast breakdown of tablet and rapid absorption
of drug into the dissolution media.
The drug release was found as F15>F20>F14>F10>F13>F5>F19>F9>F4>
F12> F3>F8>F18>F11>F2>F17>F16>F7>F1>F6.
The selected tablet formulations which possess the best physical quality were
Croscarmallose sodium 4% w/w (F4), Sodium starch glycolate 5% w/w (F10),
Crospovidone 5% w/w (F15) and Sodium bicarbonate + citric acid (1:2) 5% w/w
(F18). All prepared tablets followed First order release.
Stability study for F4, F10, F15 and F18 were performed at temperatures
(400C/75%RH). All the formulations showed no significant variation in all the
parameters evaluated under the test period condition.
On experimental data it was concluded that Fast dissolving tablet of
Ketoprofen would be an effective alternative approach for management of various
inflammatory disorders and pain. Formulation (F15) containing 5% w/w
Crospovidone is the most promising formulation for rapid release of Ketoprofen.
DEPT. OF PHARMACEUTICS, Dr.. H. L. T. COLLEGE OF PHARMACY. Page 181

BIBLIOGRAPHY
CHAPTER-9.
BIBLIOGRAPHY
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ANNEXURES

DEPT. OF PHARMACEUTIC, Dr.H.L.T COLLEGE OF PHARMACY. Page 195

ANNEXURES

DEPT. OF PHARMACEUTIC, Dr.H.L.T COLLEGE OF PHARMACY. Page 196

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FORMULATION AND EVALUATION OF FAST DISSOLVING

MAHAJAN ANIL ARUN

Reg. No: 09PU178

Under the guidance of

DECLARATION BY THE CANDIDATE

I hereby declare that this dissertation entitled “FORMULATION AND

EVALUATION OF FAST DISSOLVING TABLETS OF KETOPROFEN” is a

Mr. R. RAMESH, Professor.

Date: Signature of the candidate

Place: Channapatna MAHAJAN ANIL ARUN

CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled “FORMULATION AND

EVALUATION OF FAST DISSOLVING TABLETS OF KETOPROFEN” is a

bonafide research work done by MAHAJAN ANIL ARUN in partial fulfillment

of the requirement for the degree of Master of Pharmacy in Pharmaceutics.

Date: Mr. R. RAMESH

ENDORSEMENT BY THE H.O.D., PRINCIPAL/HEAD OF

This is to certify that the dissertation entitled “FORMULATION AND

Mr. R.RAMESH Mr. R.RAMESH

Declaration by the Candidate

I hereby declare that the Rajiv Gandhi University of Health Sciences,

this dissertation/ thesis in print or electronic format for academic / research

Date: Signature of the candidate

© Rajiv Gandhi University of Health Sciences, Karnataka.

I take it as a privilege to sincerely express my deep sense of gratitude and

I express my heartfelt thank to Mr. S. Murlidhar, Associate Professor,

It is my pleasure to thank Dr.T.V.Narayana, Chairman of Dr. H.L.T. College

It’s a great pleasure to utilize this unique opportunity to express my deep

I would like to take this opportunity to express my heartfelt gratitude and

I am thankful for utilizing the services of Library and Information Centre of

I am also thankful Mr. Gangadhar, Mr. Srinivas, Mrs. B. Pramila and to

I would like to thank my seniors, my juniors Nawaz, Kranthiteja, Pragnesh,

My special thanks to my classmates Naresh, Rakesh, Aakif, Sachin, Jaypal,

I am blessed indeed to have such caring and loving parents, my mother

I again thank all those who were involved in my accomplishments directly or

Place: (MAHAJAN ANIL ARUN)

Ketoprofen is non-steroidal anti-inflammatory drug; mainly used for osteoarthritis

by direct compression technique by addition of superdisintigrant like Sodium starch glycolate,

Crosscarmalose sodium, and Crospovidone in different concentration (1-5% w/w) and by

in-vitro drug release pattern.

Keywords: Ketoprofen, Solid dispersion, Direct compression, Fast dissolving Tablets,

Superdisintigrants, Effervescent method, Stability Study.

S. NO. PARTICULARS PAGE NO.

2 AIM AND OBJECTIVES 45-47

3 REVIEW OF LITERATURE 48-100

Figure No. Title Page No.

30 Dissolution Efficiency of Ketoprofen-PVP K30 &/ Ketoprofen 136

ease of administration, patient compliance, least sterility constraints and flexible

design of dosage forms.

accomplished by delivery of drugs to patients using conventional drug delivery

pharmaceutical products commonly seen in the prescription. Conventional oral drug

administration to obtain rapid and complete systemic drug absorption.

Drug absorption is defined as the process of movement of unchanged drug

from the site of administration to systemic circulation1.

Systemic drug absorption from a drug product consists of a succession of rate

process for solid oral, immediate release drug products.

The rate process include

¾ Dissolution of the drug in an aqueous environment.

¾ Absorption across cell membranes into systemic circulation.

DEPT. OF PHARMACEUTICS, Dr. H. L. T. COLLEGE OF PHARMACY. Page 1

membrane is the slowest or rate limiting step.2, 3.

Together with the permeability, the solubility behavior of a drug is a key

solubility has presented a challenge to the development of a suitable formulation for