Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore s17

“PREPARATION AND EVALUTION OF CONTROLLED RELEASE MATRIX TABLET OF ANTIDIABETIC DRUG ”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

BY PATEL HARSHALKUMAR BHARATBHAI M.Pharm, Part- I

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

RAVADA RAMESH, M.Pharm PROFESSOR DEPARTMENT OF PHARMACEUTICS Dr.H.L.T College of Pharmacy, Kengal, Channapatna-571502 2008-2009

1 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the candidate and MR. PATEL HARSHALKUMAR B. address DEPARTMENT OF PHARMACEUTICS, Dr.H.L.T. COLLEGE OF PHARMACY, KENGAL, CHANNAPATANA - 571502. BANGALORE (RURAL), KARNATAKA.

2. Name of the institution Dr.H.L.T. COLLEGE OF PHARMACY, KENGAL, CHANNAPATANA – 571502

3. Course of study & subject MASTER OF PHARMACY IN PHARMACEUTICS.

4. Date of admission to course 18TH JAN 2008

5. Title of the topic

“PREPARATION AND EVALUTION OF CONTROLLED RELEASE MATRIX TABLET OF ANTIDIABETIC DRUG”

6. Brief resume of the intended work:

2 6.1 Need for the study:

Antidiabetic agent12 which is important for the treatment of hyperglycemic disorders.

A Categories of antidiabetic drugs12 are rapid and almost completely absorbed from the GIT following oral administration, but undergoes extensive first pass metabolism. Therefore the peak plasma concentration occurs 1 to 3 hrs. After a single oral doses. The half life of elimination ranges from 2 to 4.5 hrs. In normal subject. The most common side effect observed are GIT disturbances, nausea, vomiting etc. 1

Hence it is required to design a drug delivery system which may deliver anti diabetic agents like Metformin1 in controlled manner for a prolonged period of time to circumvent the drug related side effects. Considering all these problems associated with oral administration of anti diabetic agents i.e. Metformin attempt has been made to develop matrix tablet in order to achieve a better release pattern. 1

Matrix tablet is a novel dosage form wherein drug delivery is controlled by diffusion, therefore this work is planned to formulate matrix tablet of Metformin and evaluate the tablet. It is also planned to conduct studies at different temperatures and humidity .17

Advantages of matrix tablet: -

1. Taste and odor masking of drug

2. Protection of drug against the environment (moisture, light, heat and oxidation)

3. To increase the patient compliance

4. To reduce the dose frequency

5. To have better therapeutic efficacy

6. To reduce the fluctuation in plasma drug concentration

7. To decrease the side effects

6.2 Review of Literature:

3 An explicit literature review was done by exploring through various national & international journals, official standard reference books and by surfing through various website on the internet.

1) Tapan Kumar Pal , Uttam Mandal et al. have formulate and optimized sustained release matrix tablet of Metformin HCL 500mg using Release Surface Methodology using HPMC K15M and PVP K30.1

2) Mutalik Srinivas and Haremath doddaya have formulate and evaluate of Chitosan matrix tablet of Nifedipine by wet granulation method using water, PVP, ethyl cellulose and shellac solution and have carried out dissolution test in simulated gastric acid fluid of PH 12.2

3) S.Vidyadhara has worked on development of controlled release matrix tablet of Propranolol HCL using HPMC as polymer along with electrolytes. At concentration of 1:1.5, electrolyte are used in different concentration for various formulation.3

4) K.P.R.Chowdary et al. has worked on formulation and evaluation of Olibanum and its resin as rate controlling matrix for controlled release of Diclofenac. In- vitro studies was carried out in phosphate buffer of pH 6.8 showing incorporation of Olibanum and its resin component provide slow and controlled release of Diclofenac over more than 24 hrs. 4 5) P. Vasantha Lakshmi et al., carried in-vitro evaluation of controlled release tablets of Nifedipine using 900m1 of HCL buffer of pH 1.2 for first 2hrs and phosphate buffer of pH 7.2 up to 8 hrs as dissolution media. 5 6) Kale V.V. et al., has shown the effect of matrix geometry on drug release from

guar gum matrix tablet, using dissolution medium as 900ml of distilled waters. 6 7) S.C. Basak et al., studied the development and in-vitro evaluation of an oral floating matrix tablet formulation of Ciprofloxacin using 900m1 of O.IN HCL as dissolution medium. 7 8) Pandey V.P., Suresh Kumar D. et. al., studied release pattern of Salbutamol Sulphate from matrix tablet formulation using various polymers along with

4 starch. In vitro studies were conducted for 2 hours in 0.1N HCL and for 6 hours in buffer medium of PH 7.2 .15

6.3 Objectives of the Study: The objectives of proposed study are: 1. To formulate matrix tablet of antidiabetic using different rate controlling polymer like hydroxyl propyl methyl cellulose (HPMC), Polyvinyl pyrrolidine (PVP), ethyl cellulose (EC), Chitosan, etc.for optimum delivery of antidiabetic drug. 2. To evaluate for pre-compression characteristics like Bulk Density, Tapped Density, Angle of Repose, Carr’s Index, and Compressibility Index for tablet mixture. 3. To evaluate the tablet for various tablet characteristic like Hardness, Thickness, Weight Variation, friability, content Uniformity and Assay. 4. To perform In-vitro dissolution studies and compare with conventional tablets. 5. To perform the stability studies at various temperatures as per ICH guidelines.

7. Materials and Methods: Materials:- 1) Drug: Antidiabetic 2) Polymers: hydroxyl propyl methyl cellulose (HPMC), Polyvinyl pyrrolidine (PVP), Ethyl cellulose (EC), Chitosan, etc.

Method:-  Wet granulation  Dry granulation  Direct compression method, etc.

7.1 Source of Data: 5 The preliminary data required for the experimental study was obtained from:

1. CD-Rom search available at national Center for Scientific Information (NCSI). Indian Institute of Sciences, Bangalore; Dr.H.L.T. college of pharmacy library; Scientific abstracts; Journals; Internet sources; Relevant books.

2. The data will be collected by laboratory investigation at Pharmaceutics Department Laboratory of Dr. HLTCP and recording observation. Matrix tablet shall prepare by using suitable methods.

7.2 Method of collection of data : (Including sampling procedure, if any) Core and coat tablets shall prepare by using various polymers like hydroxyl propyl methyl cellulose (HPMC), Polyvinyl pyrrolidine (PVP), ethyl cellulose (EC), chitosan, etc.The effect of these polymers and their ratios on drug release shall be studied.

1. The analytical method for the drug shall be developed and validated using UV- Spectrophotometer(UV-1700 SHIMADZU,JAPAN)

2. The formulation shall be evaluated for pre-compression characteristics like Bulk Density, Tapped Density, Angle of Repose, Carr’s Index, and Compressibility Index.

3. Compression characteristic and In-Vitro dissolution studies shall be carried out in the USP Dissolution Apparatus(DISSO 2000,LAB INDIA)

4. To perform the stability studies 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 mention briefly. Not applicable.

6 7.4 Has ethical clearance been obtained from your institution in case of 7.3? Not applicable.

8. List of References: 1. Tapan Kumar Pal and et al. , “Formulation and Optimization of Sustained Release Matrix Tablet of Metformin HCL 500mg using RESPONSE SURFACE METHODOLOGY”, Yakugaku Zasshi, 127(8), 1281-1290 (2007) © 2007 The Pharmaceutical Society of Japan

2. Mutalik Srinivas and Haremath Doddaya,”Formulation and Evaluation of Chitosan Matrix Tablet of Nifedipine", The Eastern Pharmacist, February 2000, volume-XLIII, no.-506, page: 109-111. 3. S. Vidyadhara and et al., “Development and In-vitro Kinetics of Propranolol HCL Controlled Release Matrix Tablets", The Indian Pharmacist, February 2006, volume-V, no.-44, page: 66-70. 4. K.P.R. Chowdary and et al., “Evaluation of Olibanum and its Resin as Rate Controlling Matrix for Controlled Release of Diclofenac", Indian Journal of Pharmaceutical Sciences, July-Aug. 2006, volume-68, no.-4, page: 497-500. 5. P. Vasantha Lakshmi and et al., “In-vitro Evaluation of Controlled Release Tablets of Nifedipine", The Indian Pharmacist, October 2005, volume-4, no.-40, page: 71-73.

6. Kale V. V. and et al., " Effect of Matrix Geometry on Drug Release from Guar gum Matrix Tablet", Indian Drugs, February 2005, volume-42, no.- 2, page: 84-86

7. S. C. Basak and et al., “Development and In-vitro Evaluation of an Oral Floating Matrix Tablet Formulation of Ciprofloxacin", Indian Journal of Pharmaceutical Sciences, May- June 2004, volume-66, no.-3, page: 313-316.

8. Yie. W. Chein, Novel Drug Delivery System, 2"d edition, Revised and Expanded, Volume- 50, Marcel Dekker Inc. Madison, New York, page: 8-12. 9. Robinson. Lee, Controlled Drug Delivery, Fundamental and Applications, 2"d edition,

7 Revised and Expanded, Volume- 29, Marcel Dekker Inc. Madison, New York, page: 373-412. 10. Donald L. Wise, Hand book of Pharmaceutical Controlled Release Technology, First Indian Reprint, Marcel Dekker Inc. Madison, New York, page:192-204

11. James Swarbick, Boylan, Encyclopedia Of Pharmaceutical Technology, 2nd edition, Volume - 3, Marcel Dekker Inc. Madison, New York, page: 26692688, 2701-2731, 2766-2789. 12. Goodman and Gilman, The Pharmacological Basis Of Therapeutics, 10 th edition, Mc Graw Hill, Page: 1705-1706, 1942. 13. Martindale, The Complete Drug Reference, 34th edition, Pharmaceutical Press, Page: 188-192, 333, 1438-1439.

14. Rowe, Sheskey, Weller, Hand Book Of Pharmaceutical Excipients, 4 t h edition, Pharmaceutical Press Page:132-135, 271-273, 323-331

15. Pandey V. P, Suresh Kumar D. et al., "RELEASE PATTERN OF SALBUTAMOL SULPHATE FROM MATRIX TABLET FORMULATION" The Indian Pharmacist Oct 2003, volume-2, no.-16.

16. G. V. Murali, Mohan Babu et al.," PREPARATION AND EVALUATION OF INDOMETHACIN-ETHYL CELLULOSE POLYMER MATRIX SYSTEM BY USING SOLVENT EVAPORATION TECHNIQUE" The Eastern Pharmacist, April 2000, volume-XLIII, no.-508, page-113-115.

17. Roland A.Bodmeier "ENCYCLOPEDIA OF PHARMACEUTICAL TECHNOLOGY second edition, Volume-III By page No. 812-813, 2990.

8 9. Signature of candidate

10. Remark of the guides The above given information is true and this work will be done under my guidance.

Mr. RAVADA RAMESH M.Pharm 11. Name & Designation of PROFESSOR (in block letters) DEPARTMENT OF PHARMACEUTICS 11.1 Guide Dr.H.L.T. COLLEGE OF PHARMACY KENGAL, CHANNAPATNA-571502 KARNATAKA.

11.2 Signature

Mr.G.S.Pancholi , M.sc 11.3 Co-guide (if any) Q.A.Manager.

Norris Medicines Ltd, Ankleshwar

801/P, 901/4-5 , GIDC Estate.

11.4 Signature 11.5 Head of the Department Mr. RAVADA RAMESH M.Pharm PROFESSOR DEPARTMENT OF PHARMACEUTICS Dr.H.L.T. COLLEGE OF PHARMACY KENGAL, CHANNAPATNA-571502 KARNATAKA.

11.6 Signature

12. 12.1 Remarks of the Chairman & Principal The above-mentioned information is correct and I recommend the same for approval.

12.2 Signature

9 From PATEL HARSHALKUMAR BHARATBHAI M.Pharm, PART I Dept.Pharmaceutics, Dr.H.L.T College of Pharmacy, Kengal, Channapatna. TO The Registrar (Evaluation), Rajiv Gandhi University of Health Sciences, Karnataka Bangalore, 4 t h ‘‘T’’ Block, Jaynagar, Bangalore-560 041 (Through Proper Channel)

Sub: Submission of Synopsis of Dissertation

Respected Sir,

Herewith, I am submitting synopsis of dissertation work “ PREPARATION AND EVALUTION OF CONTROLLED RELEASE MATRIX TABLET OF ANTIDIABETIC DRUG” for registration in M.Pharm (Pharmaceutics) of Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka. Kindly accept the same and acknowledge. Thanking you,

Yours Faithfully,

(PATEL HARSHAL)

Place: Channapatna Date: 24-11-2008

Guide:

RAVADA RAMESH M.Pharm, PROFESSOR DEPT OF PHARMACEUTICS, PRINCIPAL Dr. H.L.T.College of Pharmacy, Dr. H.L.T.College of Pharmacy, Kengal, Channapatna. Kengal, Channapatna. Bangalore (Rural)-571 502 Bangalore (Rural) 571502