CHARACTERISTIC STUDIES AND QUALITY

CONTROL ANALYSIS OF OLANZAPINE

Thesis submitted to St. Joseph’s college of Arts and Science (Autonomous)

in partial fulfillment of the requirements for the award of the degree of

BACHELOR OF SCIENCE IN CHEMISTRY

Submitted by

K. PADMAVATHI

(REG.NO: A15CHE31)

Under the Guidance of

Mr. K. VENGADESAN, M.Sc., M.Phil.

LECTURER

DEPARTMENT OF CHEMISTRY

GRADUATE DEPARTMENT OF CHEMISTRY

ST. JOSEPH’S COLLEGE OF ARTS AND SCIENCE (AUTONOMOUS)

CUDDALORE - 607001.

APRIL - 2018
 CERTIFICATE
This is to certify that thesis entitled “CHARACTERISTIC STUDIES
AND QUALITY CONTROL ANALYSIS OF OLANZAPINE”, Submitted to
St. Joseph’s college of Arts and Science (Autonomous) in partial fulfillment for the
award of the Degree of Bachelor of Science in Chemistry is bonafide record of
work carried out by K. PADMAVATHI (A15CHE31) under the guidance for the
academic period 2017 – 2018.

Signature of the guide EXTERNAL EXAMINER

(Mr. K. VENGADESAN)

Sign of the head of the department

PRINCIPAL

Viva – vioce examination held on ……………………………

 ACKNOWLEDGEMENT

I praise the “GOD ALMIGHTY” from the depth of my heart who has been a
unfailing source of strength, comfort and support.

I taken this golden opportunity to express my sincere thanks and gratitude to

our institution and secretary Rev. FR. G. PeterRajendiran, M.A., M.Sc.,
M.Ed., M.phil., St. Joseph’s college of Arts and Science, (Autonomous)
Cuddalore for graning me a permission to undertake the dissertation work.

I am extremely grateful to and thankful to Mr. A. Amalorpavadoss,

M.Sc., B.Ed., M.phil., professor and head of the department of chemistry, St.
Joseph’s college of Arts and Science, Cuddalore for his valuable support towards
the successful completion of this work.

Whole heartedly, I express my deep sense of gratitude thanks and sincerity

to my research supervisor Mr. K.VENGADESAN, M.Sc., M.phil., assistant
professor department of chemistry, St. Joseph’s college of Arts and Science,
(Autonomous) Cuddalore for his encouragement, valuable suggestions, guidance,
motivation and support at all stage in course of this study.

PADMAVATHI. K
Reg. no: A15CHE31
 DECLARATION

I hereby declare that the dissertation entitled “CHARACTERISTIC

STUDIES AND QUALITY CONTROL ANALYSIS OF OLANZAPINE”,
submitted by me for the award of degree of BACHELOR OF SCIENCE IN
CHEMISTRY (2015 – 2018) is my original work and that it not been previously
formed the basis for award of any Degree, Diploma, Associate ship, Followship or
any similar titles.

Signature of the candidate

PADMAVATHI. K
(Reg. no: A15CHE31)
 CONTENT

CHAPTER DESCRIPTION

1 INTRODUCTION

2 AIM AND SCOPE OF THE WORK

3 EXPERIMENTAL METHODS

4 QUALITY CONTROL ANALYSIS

5 RESULTS AND DISCUSSION

6 SUMMARY & CONCLUSION

7 REFERENCE
INTRODUCTION
 CHAPTER – I
INTRODUCTION
SHASUN HISTORY
 From the modest beginning in 1976 SHASUN has acquired a worldwide and
their intermediates.
 The company products are exported to customers in countries across Europe,
North America and Latin Amerce & Asia.
 SHASUN is derived from the name of the founder, late Shrishankarlal Jain
and his wife Smt. Sundarbai.
 MILESTONES
 1976 – 1990.
 Incorporated as a private limited company, Shasun chemicals in Chennai.
 First production facility established at Velachery, Chennai for manufacture
of analgin (anti pyretic).
 Second production facility was established at Puducherry for manufacture of
Ibuprofen (anti – inflammatory).
 1990 – 2000.
 Third manufacturing unit setup at Cuddalore to manufacture anti –ulcerative
ranitidine HCL.
 Shasun converted into public limited company, incorporating its present
name.
 Us subsidiary, Shasun inc., is established the company shares were listed on
Mumbai, Ahmedabad and Chennai stock exchanges.2002 – 2005.
 Board approves for hiving of its manufacturing unit manufacturing
Ibuprofen into separate joint venture company with a foreign drug major.
 From an alliance with eastiman chemical Co., Ltd of US to license the letters
technology for the manufacture of a acrylic emulsion.
 Fire accidents in one of the packing sections of Cuddalore factory.
 Obtains US FDA approval of its 3 bulk active pharmaceuticals products.
 Enters into alliances with suven pharmaceutical Ltd and innovasynth
technologies Ltd for drug discovery.
 Enters into a pact with Eli Lilly and Co., for manufacture of APL
tuberculosis.
 Brings down the average effective cost of its loans to 5% from the level 10%
in last year.
 Board approved for the issue and allotment of 9,40,000 shares on a
preferential basis.
 2007 – 2009.
 Shasun chemicals sings technology licensing agreement with lund beck.
 Shasun chemicals technology has announced that it has entered into a non
exclusive licensing agreement with merck & Co., Inc.
 Shasun chemical board recommends divided of 5 % equity share of 2/- each.
 2014.
 Shasun pharma successful completion of US FDA and Mexican COFEPRIS
inspection. Shasun pharma updates joint venture agreement with sequent
Ltd, Shasun pharma acquisition of global rights of Ibuprofen 12hr extened
release OTC & nuprin brand. Shasun & strides acrolab Ltd, have approved a
scheme of amalgamation between the two compound.
INTRODUCTION
Olanzapine, chemically known as 2 - methyl -4 - (4-methyl – 1-
piperazinyl) – 10H – thieno (2,3 – b) (1,5) benzodiazepine which is an a typical
antipsychotic medication used to treat schizophrenia and manic episodes of bipolar
disorder. Olanzapine is structurally similar to clozapine, but is classified as a
thienobenzodiazepine. The exact mechanism of action of Olanzapine is not
known. It may work by blocking receptors for several neurotransmitters
(chemicals that nerves use to communicate with each other) in the brain. It binds
to alpha – 1, dopamine, histamine H-1, muscarinic, and serotonin type 2 (5 – HT2)
receptors. Olanzapine was approved by the FDA in 1996.
Through survey of literature on the cited drug reveals that the following
methods are reported for the determination of OLZ in pharmaceutical / biological
fluids. These includes, HPLC method for the determination of OLZ in plasma,
serum, human breast milk and rat brain. High performance liquid chromatography
(HPLC) has also been used for the assay of OLZ in pharmaceutical formulations
when present either alone or in combination with fluozetine. Various other
techniques including HPTLC, capillary zone electrophoresis cyclic voltammetry,
derivative spectrometry , non aqueous titrimetry and UV – spectrophotometry and
visible spectrohotometric methods have also been reported for the assay of OLZ in
pharmaceuticals.
Many of the reported methods are time consuming, required expensive
experimental set up, and capillary zone electrophoresis and voltammetric methods
are less sensitive. Besides, the reported spectrophotometric methods suffer from
one or the other disadvantage such as lesser sensitivity, lesser stability period and
requires high acidic conditions, scrupulous control of experimental variables, time
consuming, tedious extraction procedures and heating steps.

Considering these demerits, there was a need to develop more advantageous

spectrophotometric method for the determination of OLZ in bulk and in
pharmaceutical samples. The present communication describes a highly sensitive,
rapid, simple, accurate and cost – effective spectrophotometric method for the
determination of OLZ in pure and in pharmaceutical preparations.

Active Substance:
Olanzapine which has the chemical name 2-methyl-4-(4-methyl-1-piperazinyl)- 1
0H – thieno (2,3-b)-(1-5) benzodiazepine is a yellow or off – white crystalline
solid which is not hygroscopic. Polymorphism has been observed for olanzapine.
MEDICAL USES :
Olanzapine is used to treat certain mental / mood conditions (Such as
schizolphrenia, bipolar disorder). It may also be used in combination with other
medication to treat depression. This medication can help to decrease
hallucinations and help you to think more clearly; and positively about yourself,
feel less agitated, and take a more active part in everyday life.
` Olanzapine belongs to class of drugs called a typical antipsychotics. It
works by helping to restore the balance of certain natural substances in the brain.
Talk to the doctor about the risks and benefits of treatment (especially when used
by teenagers). See also Precautions section.
OTHER USES :
This section contains used of this drug that are not listed in the approved
professional labeling for the drug but that may be prescribed by your health care
professional. Use this drug for a condition that is listed in this section only if it has
been so prescribed by your health care professional. This medication may also be
used to prevent nausea and vomiting caused by cancer drug treatment
(chemotherapy).
Read the Medication Guide provided by your pharmacist before you start
taking Olanzpaine and each time you get a refill. If you have any questions, ask
your doctor or pharmacist. Take this medication by mouth with or without food as
directed by your doctor, usually once daily.
The dosage is based on your medical condition and response to treatment.
To reduce your risk of side effects, your doctor may direct you to start this
medication at a low dose and gradually increase your dose. Follow your doctor’s
instructions carefully.
Take this medication regularly to get the most benefit from it. To help you
remember, take it at the same time each day. It is important to continue taking this
medication as prescribed even if you feel well. Do not stop taking this medication
without consulting your doctor.
PRECAUTIONS :
Before taking Olanzapine, tell your doctor or pharmacist if you are allergic
to it; or if you have any other allergies. This product may contain inactive
ingredients, which can cause allergic reactions or other problems. Talk to your
pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical
history, especially of; liver problems, seizures, difficulty swallowing, low white
blood cell count, dementia, difficulty urinating (for example, due to enlarged
prostate), glaucoma (narrow angle), stomach / intestinal disease (such as blockage,
paralytic ileus), smoking, personal or family history of diabetes, heart disease, high
cholesterol / triglyceride levels.
BEFORE USING OLANZAPINE :
Some medical conditions may interact with olanzapine. Tell your doctor or
pharmacist if you have any medical conditions, especially if any of the following
apply to you:
 If you are pregnant, planning to become pregnant, or are breast – feeding
  If you are taking any prescription or nonprescription medicine, herbal
preparation, or dietary supplement
 If you have allergies to medicines, foods, or other substances
 If you have a history of seizures, heart problems (eg, fast, slow or irregular
heartbeat; heart failure), an abnormal electrocardiogram (ECG), a heart
attack, a stroke or “mini stroke”, blood vessel problems, high blood
cholesterol levels, high or low blood pressure, or low white blood cell levels
 If you have a history of liver problems, stomach or bowel problems (eg,
decreased muscle movement), enlarged prostate, narrow – agnle glaucoma,
neuroleptic malignant syndrome (NMS), aspiration pneumonia, or suicidal
thoughts or attempts
 If you have Alzheimer disease, bowel blockage, dementia, or trouble
swallowing
 If you have diabetes or are very overweight, or if a family member has had
diabetes
 If you have had high blood prolactin levels or a history of certain types of
cancer (eg, breast, pancreas, pituitary), or if you are at risk of breast cancer
 If you are dehydrated or have low blood volume, if you drink alcohol or
smoke, or if you will be exposed to high temperatures
 If you have never taken olanzapine by mouth
OVERDOSE :
If overdose is suspected, contact a poison control centre or emergency room
right away. US residents can call their local poison control centre at 1-800-222-
1222. Canada residents can call a provincial poison control centre. Symptoms of
overdose may include: seer drowsiness / dizziness, fast / irregular heartbeat,
unusual / uncontrolled movements, seizures.
Olanzapine has a higher affinity for 5 – HT2A serotonin receptors than D2
dopamine receptors, which is a common property of all atypical antipsychotics,
aside from the benzamide antipsychotics such as amisulpride. Olanzapine also had
the highest affinity of any second generation antipsychotic towards the P-
glycoprotein in one in vitrostudy. P-glycoprotein transports a number of different
biological membranes including the blood – brain barrier, which could mean that
brain exposure to olanzapine results from this interaction with the P-glycoprotein.
SIDE EFFECTS :
Drowsiness, dizziness, lightheadedness, stomach upset, dry mouth,
constipation, increased appetite, or weight gain may occur. If any of these persist
or worsen, tell your doctor or pharmacist promptly. To reduce the risk of dizziness
and lightheadedness, get up slowly when rising from a sitting or lying position.
Remember that your doctor has prescribed this medication because he or she has
judged that the benefit to you is greater than the risk of size effects. Many people
using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including:
difficulty swallowing, shaking (tremor), signs of infection (such as fever, persistent
sore throat), slow heartbeat, fainting, mental / mood changes (such as confusion,
restlessness), numbness / tingling of arms / legs, yellowing eyes / skin, trouble
urinating.
This drug may rarely make your blood sugar level rise, which can cause or
worsen diabetes. Tell your doctor rights away if you develop symptoms of high
blood sugar, such as increased thirst and urination. If you already have diabetes,
be sure to check your blood sugars regularly. Your doctor may need to adjust your
diabetes medication, exercise program, or diet.
AIM AND SCOPE
OF THE WORK
 CHAPTER – 2

AIM AND SCOPE OF THE WORK

 To synthesis and characteristic study of Olanzapine
 To study of quality control by use of High performance liquid
chromatography for quantitative analysis of Olanzapine
 To study of quality control by the use of UV – visible spectroscopy for
quantitative analysis of Olanzapine
 To study of quality control by use of FT- IR spectroscopy for quantitative
analysis of the Olanzapine
 To check the retention time of the major peak in the chromatogram for the
sample and standard using the Chromatography method.
 To check the absorption peaks of sample with the standard using
spectroscopic method.
 To measure the moisture content, melting point, solubility and pH value to
assure the purity and good quality of the medicine Olanzapine.
EXPERIMENTAL
METHODS
 CHAPTER – 3
Experimental Section
Apparatus
All absorbance measurements were performed using a Systronics Model 166
digital spectrophotometer provided with 1 –cm matched quartz cells.
Reagents and Standards
All the chemicals used were of analytical reagent grade. All the solutions
were prepared in distilled water and freshly prepared solutions were used always.
1. N-bromosuccinimide (NBS, 4.5 x 10-3M). It was prepared by dissolving
0.08 g of NBS in hot water and dilute to 100 ml with distilled water.
2. Isonicotinic acid hydrazide (INH, 0.007M). It was prepared by
dissolving 0.096g of INH in 100 ml of distilled water
3. p-N-Methylaminophenol sulphate (Metol, 1.1 x 10-3M). Prepared by
dissolving 0.038 g of metol in 100ml of distilled water.
4. Acetic acid (2x10-3M) was used.
Standard drug solution
The pure grade OLZ certified to be 99.99 % pure was received from Cipla,
Ltd., Mumbai India as a gift sample and used as received. A stock standard
solution equivalent to 100 µg ml-1 of OLZ was prepared by dissolving 10 mg of
the pure drug in 2 M HCl and made up to 100 ml with distilled water. Working
solutions were prepared as required by dilution from the stock solution.
Procedure for calibration graph
Various aliquots of standard drug solution in the range 0.0, 0.1,0.2, 0.4,
0.8,…2.0 ml of standard OLZ (100 µg ml-1) solution was transferred into a series
of 25 ml volumetric flasks. To this was added 2 ml of NBS and the total volume in
each flask was made up to 4 ml with DMF:H2O (1:9) and kept for 10 min at room
temperature. Then, 5 ml of acetic acid and 3 ml of metol solution were added
successively. After 1 min, of INH was added and the volume was made up to the
mark with methanol and mixed well. The absorbance was measured against
distilled water at 610 nm during the stability period of 5-40 min. A blank
experiment was conducted by omitting drug. The decrease in absorbance of drug
solution from the blank. The calibration curve was constructed by taking the
difference in absorbance against the concentration of OLZ. The amount of drug
was computed from the concurrent calibration curve.
Procedure for pharmaceutical sample
Ten tablets were weighed accurately and ground into fine powder. A
quantity of the powder equivalent to 20 mg of OLZ was weighed accurately into
100ml calibrated flask. To this 5 ml 2 M hydrochloric acid was added. Then, 75
ml distilled water was also added into 100 ml calibrated flask and shaken
thoroughly for about 30 min to extract the drug completely. Then, the volume was
diluted to the mark with water and mixed well and filtered using a Whatman No.41
filter paper. The filtrate containing 200 µg ml-1 of OLZ, and the appropriate dilute
solution of drug was subjected to analysis by the procedure described above.
Pharmaceutical samples of OLZ such as Olan – 10 (Micro Synapse) was
purchased from local markets and used for the study.

Results and Discussion

Chemistry of the colored product
The method developed involves the formation of a colored charge – transfer
complex in two steps. In the first step, NBS oxidize olanzapine into its oxidation
product (sulfoxide form), and in the second step, unreacted NBS oxidize metol to
form p-N-methylbenzoquinonemonoimine (PMBQMI), which react with INH to
form a colored charge – transfer complex. This is believed to be the involvement
of electron donor and acceptor property between INH and PMBQMI, respectively.
The proposed reaction pathway is depicted in Scheme 1.
Optimization of experimental variables
To establish the optimum condition for the determination of olanzapine, the
effect of temperature, time and the order of addition of reagents were studied by
means of control experiments, and are discussed below.
 Scheme 1 – Probable reaction scheme

Effect of NBS
Under optimum experimental conditions, 2 ml of NBS solution was found to
be suitable for oxidation of OLZ and its determinations.
Effects of time and temperature
The effects of time and temperature on oxidation of OLZ were studied by
conducting the oxidation at different time intervals. Oxidation time ranging from 5
to 15 min at room temperature (27+ 3oC) gave constant and reproducible
absorbance values.
Effects of pH, metol and INH
In order to study the effect of pH, the pH of the solution was maintained by
the addition of 5 ml of 2 x 10-3 M acetic acid. This helps for attaining highest
sensitivity. Use of 3 ml of metol solution and 1.5 ml of INH solution afforded the
highest absorbance value. 1 to 3 min was necessary betwee4n the addition of
metol and INH it beyond 3 min otherwise, it will results in low absorbance value.
Effect of solvent
Methanol was found to be best solvent for final dilution of the reaction
mixture. Use of water will cause the rapid reduction in the absorbance of the
colored species. Maximum color intensity attained within 5 min after final dilution
of the solution and the colored product was stable up to 40 min.
Specification
The active substance specification includes tests for description,
identification, (HPLC, IR) water content (KF), sulphated ash (Ph Eur), heavy
metals (Ph Eur), purity (HPLC), assay (HPLC), residual solvents (GC),
polymorphic form (XRD).
The specifications reflect all relevant quality attributes of the active
substance and were found to be adequate to control the quality of the active
substance. Impurities have been qualified and found to be acceptable form the
point of view of safety.
Batch analysis data of 3 batches of active substance are provided. The
results are within the specifications and consistent from batch to batch.
Stability
Four batches of olanzapine synthesized according to the defined synthetic
process were placed under ICH storage conditions (2-8oC up to 18 months and
25oC / 60 % RH up to 6 months) in double aluminium laminated bags in HPDE
containers. The parameters tested are description, identification street testing was
also performed on one batch and included acid, base, oxidative, heat and light
stress, conditions.
The proposed re – test period is justified based on the stability results when
the active substance is stored in the original packing material.
Finished Product
Film coated tablets
 Pharmaceutical Development
The aim of the development was to obtain immediate release tablets
containing qualitatively and quantitatively the same drug substance as the
innovator product, and exhibit the same bioavailability. Dissolution tests were
used as discriminating tests in order to select suitable formulations for further
derived from this strength.
The bioequivalence study was performed with the 10 mg strength. The
excipients percentage composition is similar for all strengths, the only difference is
the colouring agent. The bioequivalence study performed can be extrapolated to
the other strengths according to the “Note for Guidance on Bioavailability and
Bioequivalence”.
The excipients used are lactose monohydrate, hydroxypropylcellulose,
crospovidone, silica colloidal anhydrous, microcrystalline cellulose and
magnesium stearate. The colourants used are : Titanium, dioxide (E171), Indigo
carmine lake (E132) and Iron oxide (172).
All the excipients are well known and commonly used in the pharmaceutical
industry. Statements of the suppliers of lactose on the risk of BSE/TSE were
provided.
Olanzapine Teva film-coated tablets are packaged in oriented polyamide
(OPA) / Aluminium / Polyvinylchloride (PVC) cold formable foil – aluminium foil
blisters.
The components of the OPA/Alu/PVC films comply with Directive 2002 /
72 / AC as amended. The suitability of the packaging system was determined in
the stability studies.
 Manufacture of the Product
The manufacturing process includes blending, granulation, tabletting,
coating and packaging.
 The manufacturing process has been validated by a number of studies for the
major steps of the manufacturing process.
The batch analysis datashow that the tablets can be manufactured
reproducibly according to the agreed finished product specification, which is
suitable for control of this oral preparation.
 Product Specification
The Product Specifications include tests by validated methods for
description, identification (HPLC, TLC), identification of titanium dioxide,
indigocarmine, and iron oxide, content uniformity (HPLC), dissolution (Ph Eur),
assay (HPLC), impurities / degradation products (HPLC), microbial limit test (Ph
Eur).
Degradation products have been evaluated and found to be acceptable from the
point of view of safety.
The tests and limits of the specifications for the finished product are
appropriate to control the quality of the finished product for their intended purpose.
Batch analysis data submitted for all strengths confirm satisfactory uniformity of
the product at release.
 Stability of the Product
Batches of 2.5 ( 2 Batches), 5 (1Batch), 7.5 (1 Batch),10 (2 Batches), 15 ( 1
Batch ) and 20 (2Batches) mg film coated tablets packed in intended market
containers were placed on stability under ICH conditions (25o C / 60 % RH, 30o C /
65 % RH ) for 12 months and 40o C / 75% RH for 6 months.
Photostability study was performed on one batch of 2.5 and 5 mg tablets stored
according to Note of Guidance on photostability test.
Based on available stability data, the proposed shelf life and storage conditions as
stated in the SPC are acceptable.
Method validation
Linearity, detection and quantification limit
Under the optimized experimental conditions a linear relationship was
observed between the absorbance and concentration of drug from 0.4 – 0.8 µg ml-1
for OLZ. The optical characteristics such as absorption maxima, Beer’s law limit,
molar absorptivity and Sandell’s sensitivity are presented in Table1. The
regression analysis using method of least squared was made for the slope (b),
intercept (a) and correlation coefficient (r) obtained from different concentrations
and the results are summarized in Table 1. The calibration curve of the proposed
method is given in Fig. 2.
Accuracy and precision
The intra – day precision and accuracy of the methods developed were
evaluated by replicate analysis of drug samples at three different concentrations
(low, medium and high) (Table 2) within the working limits, each being repeated
five times. The RE (%) and RSD (%) values of intra – day studies were
satisfactory and showed that the best appraisal of the procedures in daily use. The
analytical results obtained from this investigation are summarized in Table 2 and
showed the high accuracy of the methods.

Application to analysis of pharmaceutical samples

To check the validity of the proposed method according to the ICH

guidelines30, OLZ was determined in some pharmaceutical formulations. The
results of an assay of Olan (Micro Synapse) was found to be 101.31 + 0.48 and
was statistically compared with the literature method23 by applying the Student’s
t-test for accuracy with t-value 1.012 and F-test for precision with F-values were
2.530. The results obtained showed that there is no significant difference between
the proposed and reference method23 at the 95 % confidence level with respct to
accuracy and precision. The calculated t-and F-values did not exceed the tabulated
values (t=2.77 and F=6.39).
 Table 1 – Optical characteristics and precision
Parameter Method
λmax, nm 610
Linear range (µg ml-1) 0.4 - 08
Molar absorptivity (ε), (1 mol-1 cm-1) 2.08 x 104
Sandell sensitivity (µg cm-2) 0.0151
Regression equation (Y*)
Intercept (a) -0.0018
Slope (b) 0.0663
Correlation coefficient (r) 0.9994
LOQ (µg ml-1) 0.3696
LOD (µg ml-1) 0.1219
*y=bc + a where c is the concentration of drug in µg ml-1 and y is the absorbance
at the respective λmax., Sa is the standard deviation of intercept, Sb is the standard
deviation of slope.

With respect to accuracy and precision. The calculated t-and F-values did not
exceed the tabulated values (t=2.77 and F=6.39).
Recovery study
The accuracy and precision of the proposed method were further ascertained
by performing recovery studies. Pre – analyzed tablet powder was spiked with
pure drug at three different concentrations and the total was found by the proposed
method. Each determination was repeated three times. The recovery of the pure
drug added was quantitative and revealed that frequently encountered common
ingredients of formulations were found not to interfere. The results of recovery
study are compiled in Table 3.
Table 2 – Evaluation of accuracy and precision (within – day)
Drug Drug Drug RE SD RSD ROE**
Studied taken in found* in % (µg ml-1) % %
(µg ml-1) (µg ml-1)
2 2.031 1.53 0.046 2.278 +2.276

OLZ 4 3.952 1.19 0.026 0.669 +0.668

6 5.924 1.27 0.060 1.007 +1.006
RE: Relative error; SD: Standard deviation; RSD : Relative Standard
deviation; ROE : Range of error,
*Mean value of five determinations,
*At the 95% confidence level for 4 degrees of freedom.

Table 3 – Results of recovery by standard – addition method

Tablet Labeled Tablet Pure drug Total % Recovery +
Studied Amount, added added found* S.D
mg/tab (µg ml-1) (µg ml-1) (µg ml-1)
Olan 5 1 2 3.05 102.41+0.41
(Micro 1 4 5.02 100.45+0.50
Synapse) 1 6 7.06 101.06+0.53
*Mean of three determinations
Conclusions
The present study describes a sensitive method for the determination of OLZ
without interference from common tablet excipients. The proposed
spectrophotometric method is simple, sensitive, accurate, precise, reproducible and
economical and can be successfully applied to the routine estimation of Olanzapine
in bulk and in pharmaceutical preparations. The value of relative standard
deviation was Satisfactory low and recovery was close to 100 % which indicates
the reproducibility of the developed method for routine quality control analysis is
well established by the assay of OLZ in bulk form as well as pharmaceutical
preparations.

Acknowledgements
The authors are grateful to Cipla, India Ltd, for the generous supply of pure drug
sample. The authors are thankful to the University of Mysore, Mysore of
providing necessary facilities.
Ultraviolet – Visible Spectroscopy :
Ultraviolet – Visible spectrometry (UV – V is or UV / V is) refers to
absorption spectroscopy or reflectance spectroscopy in the ultraviolet – visible
spectral region. This means it uses light in the visible and adjacent (near – UV and
near – infrared (NIR)) ranges. The absorption or reflectance in the visible range
directly affects the perceived color of the chemicals involved.
PRINCIPLE OF UNTRAVIOLET – VISIBLE ABSORPTION :
Molecules containing – electrons or non – bonding electrons can absorb the
energy in the form of ultraviolet or visible light to excite these electrons to
higheranti – bonding molecular orbital. The more easily excited the electrons (i.e.
lower energy gap between the HOMO and the LUMO), the longer the wavelength
of light it can absorb.
An example of a UV / V is readout
UV / visible spectroscopy is also used in the semiconductor industry to
measure the thickness and optical prosperities of thin films on a wafer. UV – Vis
spectrometers are used to measure the reflectance of light, and can be analyzed via
a forouhi – Bloomer dispersion equations to determine the index of regraction (n)
and the extinction coefficient (k) of a given film across the measured spectral
range. The method is most often used in a quantitative way to determine
concentrations of an absorbing species in solution, using the Beer – Lambert law:
A = log10(Io/I) = εcL,

UV / visible spectroscopy is routinely used in analytical chemistry for the

quantitative determination of different analysis such as transition metal irons
highly conjugated organic compounds, and biological macromolecules.
Spectroscopic analysis is commonly carried out in solutions but solids and gases
may also be studied.

INSTRUMENTATION :-
An instrument is a device that measures a physical quantity such as flow,
temperature, level, distance, angle, or pressure. Instruments may be as simple as
direct reading thermometers or may be complex multi – variable process analyzers.
PRISM :-
In optics, a prism is a transparent optical element with flat, polished surfaces
that refract light. At least two of the flat surfaces must have an angle between
them. The exact angles between the surfaces depend on the application.
DIFFRACTION GRATING :-
In optics, a diffraction grating is an optical component with a periodic
structure, which splits and diffracts light into several beams travelling in different
directions.
FILTER :-
In signal processing, a filter is a device or process that removes from a signal
some unwanted component or feature filtering is a class of signal processing, the
defining feature of filters being the complete or partial suppression of some aspect
of the signal.
DETECTOR :-
In electronics, a detector is an order term for an electronic component in a
radio receiver that recovers information contained in a modulated radio wave.
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)

It is a technique in analytical chemistry used to separate, identify and

quantify each component in a mixture. It relies on pumps to pass a pressurized
liquid solvent containing the sample mixture through a column filled with a solid
adsorbent material. Each component in the sample interacts slightly differently
with the absorbent material, causing different flow rates for the different
components and leading to the separation of the components as they flow out the
column.
 HPLC has been used for manufacturing (e.g during the production process
of pharmaceutical and biological products), legal (e.g detecting performance
enhancement drugs in urine), research (e.g separating the components of a complex
biological sample, or of similar synthetic chemicals from each other), and medical
(e.g detecting vitamin D levels in blood serum) purposes. Chromatography can be
described as a mass transfer process involving adsorption. HPLC relies on pumps
to pass a pressurized liquid and a sample mixture through a column filled with a
sorbent, leading to the separation of the sample components. The active
component of the column, the sorbent, is typically a granular material made of
solid particles (e.g silica, polymers, etc.), 2-50 micrometers in size. The
components of the sample mixture are separated from each other due to their
different degrees of interaction with the sorbent particles. The pressurized liquid is
typically a mixture of solvents (e.g water, and / or methanol) and is referred to as a
“mobile phase”. Its composition and temperature play a major role in the
separation process by influencing the interactions taking place between sample
components and sorbent. These interactions are physical in nature, such as
hydrophobic (dispersive), dipole – dipole and ionic, most often a combination.
HPLC is distinguished from traditional (“low pressure”) chromatography
because operational pressures are significantly higher (50 – 350 bar), while
ordinary liquid chromatography typically relies on the force of gravity to pass the
mobile phase through the column. Due to the small sample amount separated in
analytical HPLC, typical column dimensions are 2.1 0- 4.6 mm diameter, and 30 –
250 mm length. Also HPLC columns are made with smaller sorbent particles (2-
50 micrometer in average particle size). This gives HPLC superior resolving
power (the ability to distinguish between compounds) when separating mixtures,
which makes it a popular chromatographic technique.
PRINCIPLE OF HPLC
 The principle of separation in normal phase mode and reverse phase mode is
adsorption.
 When a mixture of components are introduced into a HPLC column, they
travel according to their relative affinities towards the stationary phase.
  The component which has more affinity towards the adsorbent, travels
slower.
 The component which has less affinity toward the stationary phase travels
faster.
 Since no two components have the sane affinity towards the stationary
phase, the components are separated.

The schematic of a HPLC instrument typically includes a sampler, pumps,

and a detector. The sampler brings the sample mixture into the mobile phase
stream which carries it into the column. The pumps deliver the desired flow and
composition of the mobile phase through the column. The detector generates a
single proportional to the amount of sample component emerging from the column,
hence allowing for quantitative analysis of the sample components. A digital
microprocessor and user software control the HPLC instrument and provide data
analysis. Some models of mechanical pumps in a HPLC instrument can mix
multiple solvents together in ratios changing in time, generating a composition
gradient in the mobile phase. Various detectors are in common use, such as
UV / V is, photodiode array (PDA) or based on mass spectrometry. Most HPLC
instruments also have a column oven that allows for adjusting the temperature the
separation is performed at.
CHARACTERISTIC FEATURES OF HPLC:-
1. High resolution power.
2. Speed of separation
3. Accurate quantitative measurement
4. Continuous monitoring of the column effluent
5. Repetitive and reproducible analysis using the column and
6. High performance liquid chromatography has promoted the discovery of ion
chromatography and supercritical fluid chromatography
INSTUMENTATION OF HPLC :-
A typical modern liquid chromatography consists of the following components:
1. Solvent delivery system which includes a pump
2. Sample injection system
3. Column
4. Solvent detector and
5. Recorder
COMPONENTS :-
1. PUMPS :
A pump is a device that moves fluids (liquids or gases), or sometimes
slurries, by mechanical action. Pumps can be classified into three major groups
according to the method thy use to move the fluid: direct lift, displacement, and
gravity pumps.
2. COLUMN :
A column or pillar in architecture and structural engineering is a structural
element that transmits, through compression, the weight of the structure above to
other structural elements below. In other words, a column in compression
member.
3. DETECTOR :
In HPLC the function of detector monitor the mobile phase as it emerges
from the column. Unlike gas chromatography, HPLC has no reliable detection
system.
Ultraviolet Absorbance Detectors :
UV detectors are the most popular and are commercially available for HPLC
use in a variety of configurations.
4. RECORDER :
The signals from the detectors are recorded as deviation from a base line.
Two open recorder are used with instruments having two detectors. The peak
position along the curve relative to the starting point denotes the particular
component with proper calibration. The height or area of peak is a measure of the
amount of the component present in the sample.
Performances :
Column efficiency is defined in terms of number of theoretical plates per meter (N)
by the expression. N= 5.54 V/L.W
Where,
V= distance along the baseline between the point of injection and A perpendicular
dropped from the maximum peak.
L= Length of the column in meters.
W= Width of the peak at half peak height.
Resolution factor (Rs) between the measure peaks in the chromatogram should be
greater than 1.0 and is given by
(VRB – VRS)
Rs = 1.18 ------------------
(Whs – Whb)
Where,
V & W are the distance along the base between the point of injection and
perpendicular drawn from the maximum of two adjacent peaks. W and W are the
peak width measured at half peak height.

APPLICATIONS OF HPLC TO PHARMACEUTICAL DRUGS :

Psychoactive pharmaceuticals of the type barbiturates, benzodiazepine,
derivatives etc…., can be separated on C – 18 reversed phases.
Advantages of HPLC :
1. High speed
2. High resolution
3. High sensitivity
4. High accuracy and
5. Automated system
INFRARED SPECTROSCOPY :
Infrared spectroscopy (IR spectroscopy or Vibrational Spectroscopy) is the
spectroscopy that deals with the infrared region of the electromagnetic spectrum,
that is light with a longer wavelength and lower frequency than visible light. It
covers a range of techniques, mostly based on absorption spectroscopy. As with
all spectroscopic techniques, it can be used to identify and study chemicals. For a
given sample which may be solid, liquid, or gaseous, the method or technique of
infrared spectroscopy uses an instrument called an infrared spectrometer (or
spectrophotometer) to produce an infrared spectrum. A basis IR spectrum in
essentially a graph of infrared light absorbance (or transmittance) on the vertical
axis vs. frequency or wavelength on the horizontal axis. Typical units of frequency
used in IR spectra are reciprocal centimeters (sometimes called wave numbers),
with the symbol cm -1. Units of IR wavelength are commonly given in
micrometers (formerly called “microns”), symbol µm, which are related to wave
numbers in reciprocal. A common laboratory instrument that uses this technique is
Fourier transform infrared (FTIR) spectrometer. Two – dimensional IR is usually
divided into three regions; the near, mid – and – far – infrared, name for their
relation to the visible spectrum. Infrared spectroscopy exploits the fact that
molecules absorb specific frequencies that are characteristic of their structure.
These absorptions are resonant frequencies, i.e. the frequency of the absorbed
radiation matches the transition energy of the bond or group that vibrates. The
energies are determined by the shape of the molecular potential energy surfaces,
the masses of the atoms, and the associated ironic coupling.
Number of vibrational modes :-
In order for vibrational mode in a molecule to be “IR active”, it must be
associated with changes in the dipole. A permanent dipole is not necessary, as the
rule requires only a change in dipole moment. A molecule cab vibrate in many
ways, and each way is called a vibrational mode. For molecules with N number of
atoms in them, linear molecules have 3N – 5 degrees of vibrational modes,
whereas nonlinear molecules have 3N – 6 degrees of vibrational mode (also called
vibrational degrees of freedom). As an example H2O, a non- linear molecule, will
have 3x3-6=3 degrees of vibrational freedom, or modes.
Simple diatomic molecules have only one bond and only one vibrational
band. If the molecule is symmetrical, e.g N2, the band is not observed in the IR
spectrum, but only in the Raman spectrum. A symmetrical diatomic molecules,
e.g. CO, absorb in the IR spectrum. More complex molecules have many bonds,
and their vibrational spectra are correspondingly more complex, i.e. big molecules
have many peaks in their IR spectra.
The atoms in a CH2x2 Group, commonly found in organic compounds and
where X can represent any other atom, can vibrate in nine different ways. Six of
these involve only the CH2 portion: Symmetric and ant symmetric stretching,
scissoring, rocking, wagging and twisting, as shown below. Structures that do not
have the two additional X groups attached have fewer modes because some modes
are defined by specific relationships to those other attached groups.
For example, in water, the rocking, wagging, and twisting modes do not
exist because these types of motions of the H represent simple rotation of the
whole molecule rather than vibrations within it. These figures do not represent the
“recoil” of the C atoms, which, though necessarily present to balance the overall
movements of the molecule, are much smaller than the movements of the lighter H
atoms.
Special effects
The simplest and most important IR bands arise from the “normal modes”,
the simplest distortions of the molecule. In some cases, “overtone bands” the
observed. These bands arise from the absorption of a photon that leads to a doubly
excited vibrational state. Such bands appear at approximately twice the energy of
the normal mode. Some vibrations, so called combination modes,” involve more
than one normal mode. The phenomenon of Fermi resonance can arise when two
modes are similar in energy; Fermi resonance results in an unexpected shift in
energy and intensity of the bands etc.
INSTUMENTATION:-
In order for a vibrational mode in a molecule to be “IR active”, it must be
associated with changes in the dipole. A permanent dipole is not necessary, as the
requires only a change in dipole moment.
A molecule can vibrate in many ways, and each way is called a vibrational
mode. For molecules with N number of atoms in them, linear molecules have
3N – 5 degrees of vibrational mode, whereas nonlinear molecules have 3N – 6
degrees of vibrational modes (also called vibrational Degree of freedom). As an
example H2O, a non-linear molecule, will have 3x3-6=0 degrees of vibration
freedom, or modes.
QUALITY CONTROL
ANALYSIS
 CHAPTER – 4

QUALITY CONTROL ANALYSIS (QC)

Quality control for short, is process by which entities review the quality of
all factors involved in production. ISO 9000 defines quality control as “ A part of
quality management focused on fulfilling quality requirements”. This approach
places an example on three aspects:
1. Elements such as controls, job management, defined and well managed
processes, performance and integrity criteria, and identification of records
2. Competence, such as knowledge, skills, experience, and qualifications
3. Soft elements, such a personnel, integrity, confidence, organizational
culture, motivation, team spirit, and quality relationships.
Controls include product inspection, where every product is examined
visually, and often using a stereo microscope for fine details before the product is
sold into the external market. Inspectors will be provide with lists and descriptions
of unacceptable product defects such as cracks or surface blemishes for example.
The quality of the outputs is at risk if any of these aspects is deficient in any
way.
Quality control emphasized testing of products to uncover defects and
reporting to management who make the decision to allow or deny product release,
whereas quality assurance attempts to improve and stabilize production (and
associated processes) to avoid, or at least minimize, issues which led to the
defect(s) in the first place.
For contract work, particularly work awarded by government agencies,
quality control issues are among the top reasons for not renewing a contract.
Notable approaches to quality control:
There is a tendency for individual consultants and organizations to name
their own unique approaches to quality control a few of these have ended up in
widespread use:
 Terminology Approximate Description
year of first
use
Statistical quality 1930s The application of statistical methods
control (SQC) (specifically control charts and acceptance
sampling) to quality control
Total quality control 1956 Popularized by Armand V. Feigenbaum in
(TQC) a Harvard Business Review article and
book of the same name. Stresses
involvement of departments in addition to
production (e.g accounting, design,
finance, human resources, marketing,
purchasing, sales).
Statistical process 1960s The use of control charts to monitor an
control (SPC) individual industrial process and feedback
performance to the operators responsible
for the process. Inspired by control
systems.
Company – wide 1968 Japanese – style total quality control
quality control
(CWQC)
Total Quality 1985 Quality movement originating in the
Management united states Department of Defense that
(TQM) uses (in part) the techniques of statistical
quality control to drive continuous
organizational Improvement.
Six Sigma (6α) 1986 Statistical quality control applied to
business strategy Originated by Motorola.
Quality control in project management :
In project management, quality control requires the project manager and the
project team to inspect the accomplished work to ensure its alignment with the
project scope. In practice, projects typically have a dedicated quality control team
which focuses on this area.
1.0 DESCRIPTION :
The sample was taken in a clean watch glass. The appearance and color of
the sample was sufficient light. The odour of the material was examined by
smelling it. The observation were noted.
2.0 SOLUBILITY :
Solubility is the property of a solid, liquid, or gaseous chemical substance
called solute to dissolve in a solid, liquid, or gaseous solvent to form a solution of
the solute in the solvent. The solubility of a substance fundamentally depends on
the physical and chemical properties of the solute and solvent as well as on
temperature, pressure and the pH of the solution. The extent of the solubility of
substance in specific solvent is measured as the saturation concentration, where
adding more solute does not increase the concentration of the solution and begins
to precipitate the excess amount of solute. The solubility of a substance is an
entirely differently property from the rate of solution, which is how fast it
dissolves.

Most often, the solvent is a liquid, which can be substance or a mixture.

One may also speak of solid solution, but rarely of solution in a gas (see vapor –
liquid equilibriuminstead). The extent of the solubility ranges widely, from
infinitely soluble (without limit) (fully miscible) such as ethanol in water, to poorly
soluble, such as silver chloride in water. The term insoluble in often applied to
poorly or very soluble compounds. A common threshold to describe something as
insoluble is less than 0.1 g per 100ml of solvent.
 Under certain conditions, the equilibrium solubility can be exceeded to give
a so called supersaturated solution, which is mestastable. Metastability of crystals
can also lead to apparent differences in the amount of a chemical that dissolves
depending on its crystalline form or particle size. A supersaturated solution
generally crystallizes when ‘seed’ observable substance when fully melted and
then cooled below its fusion point.
Solubility is not to be confused with the ability to ‘dissolve’ a substance,
because the solution might also occur because of a chemical reaction. For
example, zinc ‘dissolves’ (with effervescement reaction. The zinc ions are soluble
in the acid.
The smaller a particle is, the faster it dissolves although there are many
factors to add to this generalization. Crucially solubility applies to all areas of
chemistry, geochemistry, inorganic, physical, organic and biochemistry. In all
cases it will depend on the physical conditions (temperature, pressure and
concentration) and the enthalpy and entropy directly relating to the solvents and
solutes concerned. By far the most common solvent in chemistry is water which is
a solvent for most ionic compounds as well as a wide range of organic substances.
This is a crucial factor in acidity / alkalinity and much environment and
geochemical work.
3.0 IDENTIFICATION :-
UV ABSORPTION SPECTRUM :-
Ultraviolet – visible spectrometry (UV – V is or UV / V is) refers to
absorption spectroscopy or reflectance spectroscopy in the ultraviolet – visible
spectral region. This means it used light in the visible and adjacent (near – UV and
near – infrared (NIR) ranges. The absorption or reflectance in the visible range
directly affects the perceived color of the chemicals involved. In this region of the
electromagnetic spectrum, molecules undergo electronic transitions. This
technique is complementary to fluorescence spectroscopy, in that electronic
fluorescence deals with transitions from the excited state to the ground state, while
absorption measures transitions from the ground state to the excited state.
Calculation
Absorptive differences in 230nm and 310nm is calculated as follows:

Sample Absorbance Standard Weight

Difference% = (---------------------- X ------------------------- X 100) – 100
Standard Absorbance Weight of sample

0.468 0.10070g
Percentage difference at 230 = ( -------------- X --------------- * 100) – 100
482 0.10075g

= 0.68 %

0.473 0.10070g
Percentage difference at 310 = (-------------- X --------------- X 100) – 100
0.472 0.10075g
= 1.76 %
MELTING POINT :
The melting point (or, rarely, liquefaction point) of a solid is the temperature
at which it changes state from solid to liquid at atmosphere pressure. At the
melting point the solid and liquid phase exist in equilibrium. The melting point of
a substance depends on pressure and is usually specified at standard pressure.
When considered as the temperature of the reverse change from liquid to solid, it is
referred to as the freezing point or crystallization point. Because of the ability of
some substance to super cool, the freezing point is not considered as a
characteristic property of a substance. When the “characteristic freezing point” of
a substance is determined, in fact the actual methodology is almost always “the
principle of observing the disappearance rather than the formation of ice”, that is,
the melting point. Of the sample was found to the 190o C – 195o C.
Melting point (in blue) and boiling points (in pink) of the first eight
carboxylic acids (oC) for most substance, melting and freezing points are
approximately equal. For example the melting point and freezing point mercury is
234.32 kelvins (-38.83 o
C or – 37.89o F). However, certain substances possess
differing solid – liquid transition temperature for example, agar melts at 85 oC
(185oF) and solidifies from 31o C to 40 oC (89.6oF to 104oF); such direction
dependence is known as hysteresis.
The melting point of ice at I atmosphere of pressure is very close 0o C (32oF,
237.15K); this is also known as the ice point. In the presence of nucleating
substances the freezing point of water is the same as the melting point, but in the
absence of water can super cool to – 42oC (-43.6oF, 231 K) before freezing.
The chemical element with the highest melting point is tungsten, at 3687 K
(3414 oC, 6177oF) making it excellent for use as filaments in light bulbs. The often
– cited carbon does not melt at ambient pressure but sublimes at about 4000 K; a
liquid phase only exists above pressures of IMPa and estimated 4300 – 4700 K
(see Carbon phase diagram). Tantalum hafnium carbide (Ta4HfC5( is a refractory
compound with a very high melting point of 4215K (3942oC, 7128oF). At the
other end of the scale, helium does not freeze at all at normal pressure, even at
temperatures very close to absolute zero; pressures over 20 times normal
atmospheric pressure are necessary.
4.0 pH of 1 % w/v acqueous solution :
1 g of sample was dissolved in 100ml of Milli – Q water. The pH of the
solution was measured using pH meter. After analysis the electrode was lifted,
cleaned properly and kept immersed in Milli – Q water.
pH determination :
pH of the olanzapine was determined by the use of pH meter which is
atomized and the pH was found to be 5.6
LOSS ON DRYING (LOD) :
Lod is a mixed Jewish – Arab city 156 km (9.3 mi) southeast of Tel Aviv in
the Centre District of Israel. At the end of 2012, it had a population of 71,060.
The name is derived from the ABiblical city of Lod, and it was a significant Judean
town from the Maccabean Period to the early Christian period. By modern times
the city had only retained a very small Jewish community, who were forced to
leave by the 1921 Arab riots. During the 1948 Arab – Israeli war most of the city’s
Arabinhabitans were expelled in the 1948 plaestinian exodus from Lydda and
Ramle. The town was resettled by Jewish immigrants, most of them regugees from
Arab countries, alongside 1,056 Arabs who remained. Israel’s main international
airport, Ben Gurion International Airport (previously known as Lydda Airport,
RAF Lydda, and Lod Airport) is located on the outskirts of the city.
Loss of Weight (w2-w3)
Loss on drying (%w/w = ---------------------------------------------------- X 100
Weight of sample (w2-w1)
Where, w1 – Empty weight of the LOD bottle
W2 = Weigh of the LOD bottle and sample before drying
W3 = Weight of the LOD bottle and sample after drying
Calculation :
Loss on drying (LOD) :
Weight of LOD bottle with sample : 82.8095g
Weight of empty LOD bottle : 81.8085g
Weight of sample : 1.0010g

After drying:
Weight of LOD bottle with sample of drying : 82.8098g
Weight of empty LOD bottle : 82.8081g
Loss of Weigh : 0.0017g

Loss of drying
Loss of drying = ---------------------------------------------------- X 100
Weight of sample
0.0017
= ------------------------------------------ X 100
1.0010
= 0.17%(w/w)
The USP specification for olanzapine is given below :
1. Description : White to pale yellow, crystalline powder practically odourless.
2. Solubility : Ethyl acetate + water.
3. Identification :
a. IR : Should exhibit the maxima only at the same wavelength as of
spectrum of the working references standard, sample in oil depression.
b. UV Absorption : Should exhibit max and min at the same wavelength as
spectrum of working references standard. Respective absorptive 1:100,000
solution of Max. absorbance at about 230nm and 310 nm do not differ by more
than 3.0 %.
4. Melting point : 190o C – 195oC
5. pH (1%w/v aqueous solution) : 4.0 to 5.6
6. Loss on drying : NMT 0.45 – 6 (w/w)
RESULTS AND
DISCUSSION
 CHAPTER – 5

RESULTS AND DISCUSSION

Based on the study of quality control of olanzapine, the following results are
obtained.
1. Description : White color, crystalline odourless
free flowing powder
2. Solubility : Water
3. Identification : UV Absorption : QC
Sample : 230nm, 310 nm
Standard : 230nm, 310nm
4. Melting point : 190oC -195oC
5. pH (1% w/v aqueous solution : 4.0 – 5.6
6. Loss on drying : 0.5 (w/w)
SUMMERY AND
CONCLUSION
 CHAPTER – 6

SUMMARY & CONCLUSION

 Characteristic study of Olanzapine and study of the various techniques in the

analysis of olanzapine chemicals and drugs Ltd. Cuddalore give a clear idea
about the instrumental analysis.
 The pH and moisture content are studied by the quality control Experiments.
The quality of the sample is checked with the reference standard by using
UV.
 The chapter deals with introduction of the industry and the compound
olanzapine.
 The second chapter enlightens the scope of the work.
 The third chapter discusses the various experimental methods involved in
the quality control studies.
 The given olanzapine sample was analyzed as procedure given in the
standard specification table and all the test gives positive response and
within the limited value.
The following results are drawn from the project work
 The given sample was found to be have 99.16 % purity. The acidity and
purity of raw materials should satisfies the required conditions.
 Ultraviolet spectrum of given sample material exhibits maximum and
minimum at the same wavelength as of working reference standard.
Hence the given materials complies as per united state pharmacopeia – interpharm
specification.
REFERENCE
 CHAPTER – 7

REFERENCE

1. Gohlke, R.S., Time – of – flight mass spectrometry and gas – liquid partition
Chromatrography. Anal. Chem. 1959,31 535- 41
2. Gohlke, R.S., McLafferty, F.W., Eartly gas chromatography / mass
spectrometry. J. Am. Soc. Mass Spectrum. 1993,4,(5),367-371.
3. Skooget.A 1. Principles of Instrumental analysis. 6th ed. Thomson Brooks /
cole.2007, 169-173.
4. Skoog, et.al. Principles of Instrumental Analysis. 6th ed. Thomson Brooks /
cole.2007,349-351.
5. Skoog, et.al. Principles of Instrumental Analysis. 6th ed. Thomson Brooks /
cole.2007, 351.
6. Dr. H. Kaur, “Introduction to chromatography”, PragathiPrakashan Press, p-37
(1989).
7. J.M. Miller, J.B. Crowther, “Analytical Chemistry in a Good Manufacturing
particles”, John Wiley & Sons, (2000).
8. Y.R. Sharma, “Elementary Organic Spectroscopy:, S. Chand and co Ltd, (2002)
9. Vecchia, CL and Tavani A. Fruits, vegetables, and human cancer. Eur. J.
Cancer 1998; 7: 3-8
10. Dey SK. Banerjee D. Chattapadhyay S and Karmaker KB. Antimicrobial
activities of some Medicinal Plants of West Bengal. International Journal of
pharma and Bio Science 2010; 1(3) : 1-10.
11. Okwu DE. Phytochemicals and vitamin content of indigenous spices of South
Eastern Nigeria. J. Sustain Agric. Environ 2004; 6: 30-34.
12. Gilani SJ. Khan SA. Siddiqui N.Verma SP, Mullick P and Alam O. Synthesis
and in vitro antimicrobial activity of novel N-(6-chlorobenzo(d) thiazon – yl)
hydrazine carboxamide derivatives of benzothiazole class. J Enzyme Inhib Med
Chem 2011; 2693) : 332 – 40
13. Babula P. Adam V. Havel L and Kizek R. “Naphtoquinenes and their
pharmacological properties”. Ceska Slov Farm 2007; 56 (3): 114-120.
14. Block JH and Beale JM. Central Nervous System Depressant. Wilson and
Gisyold’s textbook of organic medicinal and pharmaceutical chemistry.
Philadelphia, Pa: Lippincott Williams and Wilkins. 2004; p.495.
15. Perez AS, mendez JH, Barez JAG. Polarographic and spectrophotometric
determination of citrate in commercial orange and lemon drink. Food
chem….1989; 32;69.
16. Mollering H, Gruber H, Determination of citrate withcitrate lyase. Anal
Biochem. 1966; 17; 369.
17.Chinnici F, Spinabelli U, Piponi C, et al. Optimization of the determination of
orange acid and sugars in fruit juice by ion – exclusion liquid chromatography. J
Food Compost Anal. 2005; 18 ; 121.
18. 10 Wu SM, Ho YH, Wu HL, Chen SH, Ko HS, Head – column field –
amplified sample stacking in capillary electrophoresis for the determination of
cimetidine, famotidine, nizatidine, and ranitine – HCL in plasma. Electrophoresis,
2001; 22 (13) ; 2717 – 22.
19. Wu SM, Ho YH, Wu HL, Chen SH, Ko HS. Simultaneous determination of
cimetidine, famotidine, nizatidine, ranitidine and olanzapine in tablets by capillary
zone electrophoresis,Electrophoresis. 2001; 22 (130 : 2758 – 62. www.wjpps.com
Vol 3, Issue 12, 2014. 642 Zameeruddin et al. World Journal of Pharmacy and
Pharmaceutical Sciences
20. Yin – Xia Chang, Yue – Qui Qiu, Li-Ming Du, Chang – Feng Li and Min Guo.
Determination of rantidine, nizatidine, and cimetidine, olanzapine by a sensitive
fluorescent probe. Analyst, 2011; 136: 4168-4173.