1.

INTRODUCTION

FAST-DISSOLVING TABLETS

Fast-disintegrating and fast-dissolving tablets are becoming popular as novel

delivery systems for drug administration. They are more convenient for children, elderly
patients, patients with swallowing difficulties, and in the absence of potable liquids. The most
desirable formulation for use by the elderly is one that is easy to swallow easy to handle. Taking
these requirements into consideration, attempts have been made to develop a fast-disintegrating
tablet. Since such a tablet can disintegrate in only a small amount of water in the oral cavity, it is
easy to take for any age patient, regardless of time or place. For example, it can be taken
anywhere at any time by anyone who do not have easy access to water. It is also easy to dose the
aged, bed-ridden patients, or infants who have problems swallowing tablets and capsules.
Recently, many companies have researched and developed various types of fast-disintegrating
dosage forms [16, 17].

Advantage of fast disintegrating drug delivery system (FDDS): [16,17]

 Ease of administration to patients who refuse to swallow a tablet, such as pediatric and
geriatric patients, mentally ill, disabled and uncooperative.
 Convenience of administration and accurate dosing as compared to liquids.
 No need of water to swallow the dosage from, which is highly convenient feature for
patients who are traveling and do not have immediate access to water.
 Good mouth feel property of FDDS helps to change the basic view of medication as
"bitter pill", particularly for pediatric patients.
 Ability to provide advantages of liquid medication in the form of solid preparation.
 Rapid dissolution of drug and absorption, which may produce rapid onset of action.
 Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes
down into the stomach; in such cases bioavailability of drugs is increased.
  Pregastric absorption can result in improved bioavailability and as a result of reduced
dosage, improved clinical performance through a reduction of unwanted effects.

Limitations of FDDS: [16,17]

 The tablets usually have insufficient mechanical strength. Hence, careful handling is
required.
 The tablets may leave unpleasant taste and/or grittiness in mouth if not formulated
properly.

Disintegration Mechanisms: [5,7]

 The materials used as disintegrants include starches, agar, amylose, cellulose and its
derivatives, gum and its derivatives, gelatin, resins, and silicone compounds.
 A few mechanisms of action of disintegrants have been proposed. The first mechanism
is evolution of gas from an effervescent couple, e.g., sodium bicarbonate with citric acid
upon absorption of water. The expansion of gas can be enough to cause the tablet to
disintegrate.
 Another mechanism is swelling of disintegrants by absorbing water to break up the
tablet structure.
 In the tablet disintegration process, several factors may affect the disintegration. They
include the rate of water absorption, porosity of the tablet, processing parameters, and
effect of active ingredients, surfactants, binders, and lubricants. Fast disintegration
always requires fast absorption of water into the center of the tablet. Thus, having open
pore structures inside the tablets is very important for making fast dissolving tablets.
 Fig 2 : Disintegration of fast dissolving tablets

Conventional Techniques Used in the Preparation of Fast Dissolving Drug Delivery

Systems: [16,17]

1) Freeze drying / lyophilization

2) Tablet Moulding
3) Direct compression
4) Spray drying
5) Sublimation
6) Mass extrusion
Freeze drying:
A process, in which water is sublimated from the product after freezing, is called freeze
drying. Freeze-dried forms offer more rapid dissolution than other available solid products.
The lyophilization process imparts glossy amorphous structure to the bulking agent and
some times to the drug, thereby enhancing the dissolution characteristics of the formulation.
However, the use of freeze drying is limited due to high cost of the equipment and
processing. Other major disadvantages of the final dosage forms include lack of physical
resistance in standard blister packs.
Moulding: Tablets produced by moulding are solid dispersions. Physical form of the drug in
the tablets depends whether and to what extent, it dissolves in the molten carrier. The drug
can exist as discrete particles or micro particles dispersed in the matrix. It can dissolve
 totally in the molten carrier to form solid solution or dissolve partially in the molten carrier
and the remaining particles stay undissolved and dispersed in the matrix. Disintegration
time, drug dissolution rate and mouth feel will depend on the type of dispersion or
dissolution.
Direct compression: It is the easiest way to manufacture tablets. Conventional equipment,
commonly available excipients and a limited number of processing steps are involved in
direct compression. Also high doses can be accommodated and final weight of tablet can
easily exceed that of other production methods. Directly compressed tablet's disintegration
and solubilization depends on single or combined action of disintegrates, water soluble
excipients and effervescent agent. Disintegrate efficacy is strongly affected by tablet size
and hardness. Large and hard tablets have disintegration time more than that usually
required. As consequences, products with optimal disintegration properties often have
medium to small size and /or high friability and low hardness. Breakage of tablet edges
during handling and tablet rupture during the opening of blister alveolus, all result from
insufficient physical resistance.

The understanding of disintegrant properties and their effect on formulation has advanced
during last few years, particularly regarding so called superdisintegrants. Disintegration
efficiency is based on force equivalent concept, which is the combined measurement of swelling
force development and amount of water absorption.

Spray-drying: Highly porous and fine powders can be produced by spray drying, as the
processing solvent is evaporated rapidly during spray drying. Spray drying technique has been
employed to prepare fast dissolving tablets. When immersed in an aqueous medium, the tablets
compressed from spray-dried powder, disintegrated within 20 seconds.

Sublimation: Because of low porosity, compressed tablets composed of highly water-soluble

excipients as tablet matrix material often do not dissolve rapidly in the water. Porous tablets that
exhibit good mechanical strength and dissolve quickly have been developed. Inert solid
ingredients (e.g.; urea, urethane, ammonium carbonate, camphor, naphthalene) were added to
other tablet excipients and the blend was compressed into tablet. Removal of volatile material by
sublimation generated a porous structure.
Mass-extrusion: This technology involves softening the active blend using the solvent mixture
of water soluble polyethylene glycol, using methanol and 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. The dried cylinder can also be used to coat granules of bitter tasting drugs and
thereby masking their bitter taste.

Evaluation Tests For Fast Dissolving Tablet: [16,17]

Tablets from all the formulation were subjected to following quality control test.

General Appearance: The general appearance of a tablet, its visual identity and over all
“elegance” is essential for consumer acceptance. Include in are tablet’s size, shape, colour,
presence or absence of an odour, taste, surface texture, physical flaws and consistency and
legibility of any identifying marking.

Size and Shape: The size and shape of the tablet can be dimensionally described, monitored
and controlled.

Tablet thickness: Tablet thickness is an important characteristic in reproducing appearance and

also in counting by using 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.
Uniformity of weight: I.P. procedure for uniformity of weight was followed, twenty tablets
were taken and their weight was determined individually and collectively on a digital weighing
balance. The average weight of one tablet was determined from the collective weight. The
weight variation test would be a satisfactory method of determining the drug content uniformity.
Tablet hardness: Hardness of tablet is defined as the force applied across the diameter of the
tablet in the order to break the tablet. The resistance of the tablet to chipping, abrasion or
breakage under condition of storage transformation and handling before usage depends on its
hardness. Hardness of the tablet of each formulation was determined using Monsanto Hardness
tester.
Friability: It is measured of mechanical strength of tablets. Roche fribilator was used to
determine the friability by following procedure. A preweighed tablet was placed in the fribilator.
Fribilator consist of a plastic-chamber that revolves at 25rpm, dropping those tablets at distance
of 6 inches with each revolution. The tablets were rotated in the fribilator for at least 4 minutes.
At the end of test tablets were dusied and reweighed, the loss in the weight of tablet is the
measure of friability and is expressed in percentage as
%Friability = loss in weight / Initial weight x 100
Modified disintegration test: The standard procedure of performing disintegration test for these
dosage forms has several limitations and they do not suffice the measurement of very short
disintegration times. The disintegration time for ODT needs to be modified as disintegration is
required without water, thus the test should mimic disintegration in salivary contents. For this
purpose, a petridish (10cm diameter) was filled with 10 ml of water. The tablet was carefully put
in the center of petridish and the time for the tablet to completely disintegrate into fine particles
was noted.

In-Vitro Dissolution test: USP 2 Paddle apparatus was used and paddle was allowed to rotate at
50 rpm .phosphate buffer (PH 6.8) (900 ml) was used as a dissolution medium.

LITERATURE REVIEW

 Gnanaprakash et al,. prepared fast dissolving tablets of valdecoxib in the oral cavity
with enhanced dissolution rate. The fast dissolving tablets of valdecoxib was prepared
with some carriers (polymers) and super disintegrants such as polyvinyl pyrrolidone
(PVP), sodium carboxy methyl cellulose (SCMC), crospovidone NF and β –
cyclodextrin. The above mentioned all carriers and superdisintegrants were taken in
different proportions of 5, 10, and 15%. All the formulations of the fast dissolving
tablets of valdecoxib were prepared by direct compression technique. The blend was
examined for angle of repose, bulk density, compressibility index and Hausner’s ratio.
The prepared tablets were evaluated for hardness, drug content uniformity, friability,
 disintegration time and dissolution rate. The prepared formulations drug release was
found to be comparable with the marketed dispersible tablets.
 Gohel et al., developed mouth dissolving tablets of nimesulide. Granules containing
nimesulide, camphor, crospovidone and lactose were prepared by wet granulation
technique. Camphor was sublimed from the dried granules by exposure to vacuum. The
porous granules were then compressed. Alternatively, tablets were first prepared and
later exposed to vacuum. The tablets were evaluated for percentage friability, wetting
time, and disintegration time. In the investigation, a 32 full factorial design was used to
investigate the joint influence of 2 formulation variables: amount of camphor and
crospovidone. The results of multiple linear regression analysis revealed that for
obtaining a rapidly disintegrating dosage form, tablets should be prepared using an
optimum concentration of camphor and a higher percentage of crospovidone. A contour
plot is also presented to graphically represent the effect of the independent variables on
the disintegration time and percentage friability. A checkpoint batch was also prepared
to prove the validity of the evolved mathematical model. Sublimation of camphor from
tablets resulted in superior tablets as compared with the tablets prepared from granules
that were exposed to vacuum. The systematic formulation approach helped in
understanding the effect of formulation processing variables.
 Shirsand et al., prepared fast dissolving tablets of clonazepam by direct compression
method with a view to enhance patient compliance. A 32 full factorial design was applied
to investigate the combined effect of two formulation variables: amount of crospovidone
and microcrystalline cellulose. Crospovidone (2-8% w/w) was used as superdisintegrant
and microcrystalline cellulose (20-40% w/w) was used as diluent, along with directly
compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness,
friability, thickness, drug content uniformity, in vitro dispersion time, wetting time and
water absorption ratio. Based on in vitro dispersion time (approximately 16 s); the
formulation containing 2% w/w crospovidone and 40% w/w microcrystalline cellulose
was found to be promising and tested for in vitro drug release pattern (in pH 6.8
phosphate buffer). Short-term stability (at 40 degrees /75% relative humidity for 3 mo)
and drug-excipient interaction. The optimized tablet formulation was compared with
conventional commercial tablet formulation for drug release profiles. This formulation
 showed nearly five-fold faster drug release (t(50%) 3.5 min) compared to the
conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability
studies on the formulation indicated that there are no significant changes in drug content
and in vitro dispersion time (P<0.05).
 Narmada et al., formulated fast dissolving tablet of amlodipine besylate for rapid action
by sublimation method using a 23 full factorial design. FT-IR and D.T.A studies
revealed that there was no physico-chemical interaction between amlodipine besylate
and other excipients. All formulations are evaluated for pre-compression and post-
compression parameters, wetting time, water absorption ratio. The results obtained
showed that the quantity of starch potato, sodium starch glycolate, camphor significantly
affect response variables. The results indicate that the optimized tablet formulation
provides a short DT of 8 sec with sufficient crushing strength and acceptable friability.
Stability studies of optimized formulation revealed that formulation is
stable.
 Bhupendra et al., formulated directly compressible orally disintegrating tablets of
cinnarizine with sufficient mechanical integrity, content uniformity, and acceptable
palatability to assist patients of any age group for easy administration. Effect of varying
concentrations of different superdisintegrants such as crospovidone, croscarmellose
sodium, and sodium starch glycolate on disintegration time was studied. Absorption
ratio (R) for each of three superdisintegrants at concentrations studied. Considering the
‘R’ values and disintegration time, crospovidone was significantly superior compared to
other two superdisintegrants tested. Release of drug was faster from formulations
containing 6% crospovidone (CP5) compared to the marketed convetional cinnarizine
tablet. Finally concluded that directly compressible orally disintegrating tablets of
cinnarizine with lower friability, acceptable taste, and shorter disintegration times were
obtained using crospovidone at optimized concentrations.
 Ganesh kumar et al., studied about the fast dissolving tablets of chlorpromazine Hcl in
the oral cavity with enhanced dissolution rate. The tablets were prepared with five
superdisintegrants eg: Sodium starch glycolate, crospovidone, croscarmellose, L-HPC,
pregelatinised starch, The blend was examined for angle of repose, bulk density, tapped
density, compressibility index and Hausners ratio. The tablets were evaluated, It was
 concluded that the fast dissolving tablets with proper hardness, rapidly disintegrating
with enhanced dissolution can be made using selected superdisintegrants.

AIM & OBJECTIVE

Aim of the study:
The aim of present work is to develop a fast dissolving solid oral dosage form of Almotriptan.
Objectives:
Primary Objective:
1. To formulate and evaluate fast release Almotriptan.
Secondary Objectives:
1. To perform preformulation studies.
2. To develop various formulations with different super disintegrants.
3. To study the effect of excipient concentrations on the tablet characteristics.
4. To achieve fast release profile for the developed formulation.
 PLAN OF WORK

 LITERATURE SURVEY
 SELECTION OF DRUG, MATERIALS & FORMULATION DESIGN
 PREFORMULATION STUDIES
 Description
 Melting point.
 Solubility
 UV spectroscopy
 Drug – Excipient Compatibility Studies
 FORMULATION DEVELOPMENT
 EVALUATION STUDIES
 Tapped Density
 Angle of Repose
 Compressibility Index
 Hardness, thickness.
 Weight variation
 Assay
 In-vitro disintegration
 In-vitro dissolution studies
 DRUG PROFILE

ALMOTRIPTAN

Description
Almotriptan is used to treat migraines. It helps to relieve headaches, pain and other symptoms of
migraines, including sensitivity to light/sound, nausea, and vomiting. Prompt treatment allows
you to get back to your normal routine and may decrease your need for other pain medications.
Almotriptan does not prevent future migraines or reduce how often you may get a headache.
Trade name : Axert
Structure

IUPAC Name: N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine

Formula C17H25N3O2S

Mol. mass 335.465 g/mol

Mechanism of action:
Almotriptan has a high and specific affinity for serotonin 5-HT1B/1D receptors. Binding of the
drug to the receptor leads to vasoconstriction of the cranial blood vessels and thus affects the
redistribution of cranial blood flow. Almotriptan significantly increases cerebral blood flow and
reduces blood flow through extracerebral cranial vessels. Even though it affects cranial blood
vessels a single dose of almotriptan (12.5 mg) has no clinically significant effect on blood
pressure or heart rate in both young and elderly healthy volunteers. However larger doses seem
to slightly increase blood pressure but not beyond clinical relevance.

Bioavailability 70%

Protein binding 35%

Metabolism Hepatic

Half-life 3–4 hours

Pharmacokinetics:
Almotriptan has a linear pharmacokinetic up to 200 mg dose. Its half life is 3 hours and nearly
70% bioavailability.Cmax is observed 1.5–4 hours after oral administration and approximately
50% of the drug is excreted unchanged in the urine. Metabolism is mediated through MAO-A
and CYP3A4 and CYP2D6 oxidation. Almotriptan clearance is moderately reduced in the
elderly but does not require dose adjustment. Sex does not alter the pharmacokinetics of the
drug. However, patients with moderate-to-severe renal dysfunction should limit their total daily
dose to 12.5 mg.
Drug interactions:
Studies of drugs used as preventive against migraine (propranolol and verapamil), anti-
depressants (moclobemide and fluoxetine) yielded results that showed significant altering of the
pharmacokinetics of almotriptan
Side effects
Drowsiness
dizziness
nausea
sensations of tingling
numbness/prickling
dry mouth
STORAGE

Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture.

REFERENCES

 Amin PD, Gupta SS, Prabhu NB, Wadhwani AR. Fast disintegrating dosage form of
Ofloxacin and Metroniadazole benzoate. Indian Drugs 2005 Sept; 42(9): 614-17.

 Shirwaiker AA, Ramesh A. Fast disintegrating tablets of Atenolol by Dry granulation

method. Indian J Pharm Sci 2004 Jul-Aug; 66(4): 422-26.
 Ajaykumar Patil, Taqiuddin Aman, Nithin Bhargava B., Abhilash P., Madhuri Turaga,
Supriya Kulkarni. “Formulation and evaluation of mouth dissolving tablets of montelukast
sodium”. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2011; 2(3):
268.
 Keny R.V., Desouza C., Lourenco C.F. “Formulation and evaluation of rizatriptan benzoate
mouth disintegrating tablets”. Indian J Pharm. Sci. 2010; 72(1): 79-85.
 Shenoy V., Agrawal S., Pandey S. “Optimizing fast dissolving dosage forms of Diclofenac
sodium by rapidly disintegrating agents”. Indian Journal Pharm. Science. 2003; 65(3): 197-
200.
 Mahajan H.S., Kuchekar B.S., Badhan A.C. “Mouth dissolve tablets of sumatriptan
succinate”. Indian Journal of Pharm. Science. 2004; 66(2): 238-240.
 Patel D.M. and Patel M.M. “Optimization of fast dissolving eterocoxib tablets prepared by
sublimation technique”. Indian Journal of Pharmaceutical sciences. 2008; 70(1): 71-76.
 Raghavendrarao N.G., Patel T., Gandhi S. “Development and evaluation of carbamazepine
fast dissolving tablets prepared with a complex by direct compression technique”. Asian
Journal of Pharmaceutics. 2009; 97-103.
 Gnanaprakash K., Mallikarjuna Rao K., Chandra Sekhar K.B., Madhusudhana Chetty C.,
Alagusundaram M., Ramkanth S. “Formulation and evaluation of fast dissolving tablets of
valdecoxib”. International Journal of PharmTech Research(USA): 0974-4304.
 Gohel M., Patel M., Amin A., Agarwal R., Dave R., Bariya N. “Formulation design and
optimization of mouth dissolve tablets of nimesulide using vacuum drying
technique”. AAPS Pharm. Sci. Tech. 2004; 5(3): 1-6.
 Shirsand S.B., Suresh S., Swamy P.V. “Formulation design and optimization of fast
dissolving clonazepam tablets”. Indian J Pharm Sci. 2009; 71(5): 567-72.
 Narnada G. Y., Mohini K., Prakash Rao B., Kumar K. S. “Formulation, evaluation and
optimization of fast dissolving tablets containing amlodipine besylate by sublimation
method”. Ars Pharm. 2009; 50(3): 129-144.
 Bhupendra G. Prajapati and Satish N. Patel. “Formulation, evaluation and Optimization of
orally disintegrating tablet of cinnarizine”. e -Journal of Science & Technology. 2010; 5(5):
9-21.