RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM

DISSERTATION

1. Name of the candidate MOHAMMED UBAIDULLAH

And address. S/o Md.Ataullah
H.No: 1-3-63
Inside Naikaman
Bidar-585402
Karnataka
2. Name of Institution Karnataka College of Pharmacy, Bidar-585401.
3. Course of study and subject.
M.PHARM (PHARMACEUTICS).
4. Date of admission to the course
6-6-2012
5. Title of Topic:
FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF
GLIMEPIRIDE.

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6.
BRIEF RESUME OF THE INTENDED WORK:

6.1. Need for the study:

The poor dissolution of relatively water insoluble drugs as for long had been a problem
in the formulation of oral dosage forms. This limits such as absorption and Bioavailability.
Several approaches have been followed in improving solubility of the drugs, one being
microwave irradiation method to prepare a solvent-free solid dispersion1.
The oral route of drug administration is more common and convenient where tablets
and capsules emerged as popular dosage form but many patients have dysphagia or difficulty in
swallowing which is currently affecting 35% general population. From this perspective Quick
dissolving oral films offer a new and novel drug delivery system.

Quick dissolving tablets (QDT) are those, which disintegrate or dissolve or

disperse quickly in a few seconds after placement in the mouth i.e. in saliva
without the need of water, which can alleviate the problem of swallowing
tablets. This could enhance the clinical effect of drug through pre-gastric absorption from
the mouth, pharynx and oesophagus by avoiding first pass liver metabolism and useful in
administering drug in pediatric and geriatric, mentally ill, unco-operative
and nauseated patients those with condition of motion sickness2.

Glimepiride is one of the third generation sulphonylurea, antidiabetic drug which

stimulates insulin release. It is used for treatment of non-insulin-dependent diabetes mellitus.
Glimepiride is classified under class II according to biopharmaceutical classification system.
The drug shows low, pH dependent solubility. In acidic and neutral aqueous media, glimepiride
exhibits very poor solubility at 370C (<0.004 mg/ml). In media pH>7, solubility of drug is
slightly increased to 0.02 mg/ml. This poor solubility may cause poor dissolution and
unpredicted bioavailability. However, attempts have been made to improve its bioavailability3.

To increase the solubility and bioavailability, Glimepiride can be formulated in the

form of complexes with HPCD by microwave irradiation method and then further formulated
into Fast Dissolving Tablets (FDT) by Direct Compression Technique using Super-disintegrants
like Crosscarmelose Sodium, Crospovidone and Sodium Starch Glycolate.

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6.2 Review of Literature:

A thorough literature survey on the topic has been done and very prominent are.

Development of -cyclodextrin complexes of tenoxicam were tried in order to increase the

solubility features of drug. The complex prepared by neutralization method was found to yield very
reliable and best results over that of the common solvent and kneading method.4

Development of nimodipine complex with and hydroxyl propyl cyclodextrein were tried to
enhance the solubility of the drug. The solubility and dissolution rate of nimodipine were markedly
enhanced by complexazation with -cyclodextrein and Hydroxy propyl -cyclodextrin needed
complexes gave higher dissolution rate than co evaporation method.5

The design and evaluation of Hydroxy propyl -cyclodextrin with camptothecin was done to
enhance the solubility and dissolution rate the solubility of camptothecin found to increase with both
increase in PH and Hydroxy propyl -cyclodextrein concentration.6

The development of celecoxib complexes was done to enhance the inclusion complex, the
solubility and dissolution rate of celecoxib were increased. The solid inclusion complex of celecoxib
and CD were prepared by the kneading method using different molar proportions of CD.
Enhancement of dissolution rate with increasing quantity of CD in the complex was observed. It was
also observed that the complexes exhibit higher dissolution rate than the pure drug and physical
mixture.7

An attempt was made to improve the in vitro dissolution behavior of Roficoxib cyclodextrin
inclusion complexes thus enhancing its dissolution rate, their by lading to a faster onset of action and
less G I mucosal toxicity. The inclusion complex found to have improved in vitro drug release compared
with a pure drug it was also found that a significant decrease in the gastric ulcerogenic activity of the in
the complex form.8

Development of ketoprofen and natural -cyclodextrin, Hydroxy propyl -cyclodextrin

complexes was done in order to develop a new dosage form with enhanced dissolution rate and
bioavailability. The drug cyclodextrin complexes were prepared by kneading method, co-evaporation
method and freeze drying. The formation of inclusion complexes with cyclodextrin were confirmed by
differential scanning techniques like Fourier transform infrared spectroscopy,X-
diffractometry,Scanning electron microscopy studies and comperative studies on in-vitro dissolution
and in-vivo absorption of ketoprofen in human volunteers, were carried out. The initial dissolution rate
of ketoprofen in the inclusion complex was 15 Fold higher than, that of plain drug.9

An development of -cyclodextrin-Satranidazole inclusion complex was done

In order to increase the aqueous solubility and dissolution rate of drug. Phase solubility profile
indicated that the solubility of Satranidazole was significantly increased in the presence of -
cyclodextrin. The complex prepared by kneading method was characterized using differential scanning
calorimetry, powder X-ray diffractometry. In vitro study showed that the solubility and dissolution rate
of Satronidazole was significantly improved by complexation with -cyclodextrin10.

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 The fast dissolving edible film composition comprising a safe and
effective amount of a cellulose based film forming agent comprising a mixture
of atleast one low viscosity cellulose based film forming agent; where in the
film composition rapidly dissolves in the oral cavity. In one embodiment the
edible film is a breath freshening film11.

A consumable film adapted to adhere and dissolve in the oral cavity

of a warm blodded animal including humans, comprising atleast one water
soluble polymer, a taste masking effective amount of a sweetner, a mucosa-
coating effective amount of a mucosa coating agent and pharmaceutically
active agent having a sufficiently unpleasant taste that it is desirably masked
by the sweetner12.

Complexation of Glimepiride with HP-cyclodextrein has been reported, but no work has been
reported by microwave irradiation techinique. So it is planed to prepare the complexation by microwave
irradiatio technique and compare the complexes prepared by physical mixture. Further the complex is
formulated into Fast Dissolving Tablets (FDT) by Direct Compression Technique using Super-
disintegrants like Crosscarmelose Sodium, Crospovidone and Sodium Starch Glycolate.

6.3 Objective of the study:

The main objective of this work is formulation and evaluation of Glimepiride-HPCD

complex to enhance the solubility.

The major objectives of the investigation are as follows:

1] To prepare the complexes of Glimepiride using cyclodextrin by microwave irradiation method.

2] To study the phase solubility and stability constant for the intended complexes.
3] To study the dissolution performance of different complex formulations.
4] To perform Compatible studies by using IR spectroscopy.
5] To characterize the complexes for E.g., XRD, DSC etc.
6] To perform aqueous solubility and partition coefficients.
7] To formulated complex into Fast Dissolving Tablets (FDT) by Direct Compression Technique using
Super-disintegrants like Crosscarmelose Sodium, Crospovidone and Sodium Starch Glycolate.
8] To perform the characterization studies like weight variation, thickness, drug content uniformity,
disintegration test of the prepared formulations.
9] To study the in vitro drug release kinetics of the prepared formulation.
10] To perform stability studies as per the ICH guidelines.

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7. 7 MATERIALS AND METHODS:

7.1 SOURCE OF DATA:

It is mainly laboratory based methed.All the basic facilities required are available
in our college laboratories.
The survey of literature on the area of present investigation will be done by
referring to pharmaceutics abstracts, all the national and international journals.
The information about formulation and evaluation parameters will be collected by
referring to Indian journal of pharmaceutical science, Indian journal of
pharmaceutical education, European journal of pharmaceutical science, Indian
drugs, etc.
The day to day development in the area will be updated by literature survey
through e-publishing and internet. For this purpose, the library and internet facility
are available in our college.
For the drug dissolution studies, dissolution test apparatus USPXXIV is used. For
the estimation of drug UV-Visible spectrophotometer is used. For compatibility
studies IR spectrophotometer is used.
All the above facilities are availability in our college.

7.2 METHOD OF COLLECTION OF DATA:

Preformulation study like phase solubility, stability constant are performed for
complexes.
Drug content uniformity will be known by performing assay of the prepared
formulations using UV-visible spectrophotometer method at 236nm.
Compatibility studies between drug & HPCD will be carried out by IR
spectroscopy.
Drug release data of Complexes will be obtained by performing in vitro
dissolution studies using USP dissolution apparatus type II with 500ml and water
as dissolution medium at 370 C and 50 rpm.
Aqueous solubility and partition co- efficient of the complexes will be conducted.
Characterization of the complexes (DSC, XRD, SEM, etc.,) will be get it done
from the institutions where the facilities available.
Statistical analysis of data obtained from the results.
Stability studies are performed for formulation as per ICH guidelines.

7.3 Does the study require any investigation or intervention to be conducted on

patients or other humans or animals?(if so please describe briefly)

-----------Not under the plan of work--------------

7.4 Has ethical clearance been obtained from your institution in case of 7.3?
--------Not applicable------------

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8. LIST OF REFERENCES:

1) Mariarosa M, Guglielmo Z, Nicola DZ. Influence of the microwave technology on the

physical-chemical properties of solid dispersion with Nimusulide. Powder
Technology. 2009 Nov 10; 195(3): 259-263.
2) Dixit RP, Puthi SP, Oral strip technology: Over view and future potential. Journal of
controlled release 2009 June 24; 139: 94-107.
3) Kiran T, Shastri N, Ramakrishna S, Sadanandam M. Surface solid dispersion of
glimepiride for enhancement of dissolution rate. International Journal of PharmTech
Research 2009; 1(3): 822-31

4) Sanoferjan AM, Cajuns Swamy NG, Mahesh S, Narasimha

Murthy S. Formulation and Evaluation of - cyclodextrin complexes of Tenoxicam.
Indian J Pharm Sci 2000; 62 (2): 199-121

5) Chowdhary KPR & Kamalakar RG. Investigation of complexation of Nemodipin with

- cyclodextrin and hydroxy propyl - cyclodextrin. Indian Drugs 2001; 38(11): 552-
. 558

6) Ann MS, Nguyen BN, Annectte BB. & Martin B. Effect of Hydroxy propyl -
cyclodextrin complexation and PH on solubility of Camtothecin Int J pharmaceutics
2004; Vol 284, 1-2: 61-68.

7) Swati Rawat and Sanjay K Jain, Solubility enhancement of Celecoxib using -

cyclodextrin complexes. European Journal of Pharmaceutics and Biopharmacetics
Volume 57, 2, 2004, 263-267

8) Baboota S, Dhaliwal M, Kohli K., Physiochemical chemical characterization of in-

vitro dissolution behavior and Pharmaco-dynamic studies of Rofecoxib- -
cyclodextrin inclusion compounds of preparation and properties of Rofecoxib-
Hydroxy propyl -cyclodextrin inclusion complexes: A technical note. AAPS, Pharma
Sci Tech 2005-06 E83-E90.

9) Tayade PT, and Vivia PR Inclusion complex of Ketoprofen with - cyclodextrin:

Indian J Pharm Sci.,2006, 68(2): 164-170.

10) Deelip Derle, Sai Hanuman Sagar Boddu and Manoj Magar Studies of the
preparation,characterization and solubility of -Cyclodextrin inclusion complexes:
Indian j. Pharm.
Educes. Res. 40(4) Dec 2006
11) Ann AI, Rossman JM, Mark LK. Rapidly dissolving edible film compositions with
cellulose film forming polymers. US Patent 2004 Oct 14.

12) Kulkarni N, Sorg AF, Kumar LD. Fast dissolving orally combustable films. US
Patent 2008 Jan 24.

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 Signature of the candidate
9.
(MOHAMMED UBAIDULLAH)

Industry oriented technology

Remarks of the Guide

10.

11. Name and Designation of

(in block letters)

11.1 Guide
AJAYKUMAR PATIL
Asst. Prof.
Karnataka college of pharmacy
Bidar-585403.

11.2 Signature

12. Name and Designation

(In block letters)

12.1 Co Guide ------------

12.2 Signature ------------

13. 13.1 Remarks of the Chairman and

Principal.

13.2 Signature

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