Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore s20

“DESIGN AND EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEM OF ANTI DIABETIC DRUG”

DISSERTATION PROTOCOL

Submitted to the

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

BY DETROJA PURUSHARTH M. M.Pharm, PART- I

DEPARTMENT OF PHARMACEUTICS

UNDER THE GUIDANCE OF

Mr.K.SENTHIL KUMAR, M.Pharm ASSISNANT PROFESSOR DEPARTMENT OF PHARMACEUTICS Dr.H.L.T. College of Pharmacy, Kengal, Channapatna-571502 2008

1 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the candidate and DETROJA PURUSHARTH M. 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:- 12TH JAN.2008

5. Title of the topic:-

“DESIGN AND EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEM OF ANTI DIABETIC DRUG”

2 6. Brief resume of the intended work:

6.1 Need for the study:

The principle of transdermal drug delivery systems is to deliver drug across epidermis to achieve systemic effect over a prolonged period of time. Because of these attributes, transdermal drug delivery systems offer many advantages such as reduced side effects, improved patient compliance, elimination of first-pass metabolism, and sustained drug delivery. 1 More recently, there is an increasing recognition that the skin can also serve as the port of administration for systematically active drug where the drug applied topically will be first in to blood circulation and then be transported to target tissue which could be rather remote from the site of drug application to achieve its therapeutic purpose 15 The successful introduction of trandermal therapeutic system (TTS) has created extremely high interest in this route. This route of drug delivery among pharmaceutical industries and has accelerated transdermal drug delivery research activities in the field of pharmaceutics 16

Anti diabetic drug which is important for the treatment of hyperglycemic disorders. A Categories of anti diabetic drugs 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 hrs. in normal subject. The most common side effect observed are GIT disturbances, nausea, vomiting etc.

Hence, it is required to design a drug delivery system which may deliver anti- diabetic drug like Glipizide 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 drug i.e. Glipizide attempt has been made to develop transdermal drug delivery system in order to achieve a better release pattern.

3 6.2 Review of Literature:

1. Polymers are backbone of transdermal drug delivery systems. The system for transdermal delivery is fabricated as multilayered polymeric laminates in which the drug reservoir or the drug polymer matrix is sandwiched between two polymeric layers. Cellulose derivatives, polyvinyl pyrrolidone, hydroxypropyl methylcellulose matrices have been investigated for this purpose. 17

2. M.K.Das., et al.,. Have studied Transdermal Delivery of Trazodone Hydrochloride from Acrylic Films prepared from Aqueous latex, The effect of polymeric composition, Drug content an plasticizer on the permeation of trazodone HCL across the mouse epidermis for the Development of Transdermal therapeutic system 5 .

3. J. BagyaLakshmiR.,et al.,. Have studied Transdermal Delivery of Ampicillin Sodium Patch Made from Volatile Vehicle, Antinucleant polymers where used in the increased activity state of the drug 6.

4. Poonia Brijendra Singh., et al.,. Described enhancement techniques based on drug/vehicle optimization, such as physical enhancement, inconvertible prodrug, super saturation and surface active agent. They discussed about the limitations and potential for clinical applications of penetration enhancers’ .It is concluded that the penetration enhancers currently under investigation can be formulated into acceptable and nonirritant products 11

5. Subal C. Basak.,.et al.,. Have reported Transdermal patches, What

4 pharmacists need to know?. Protocols of Transdermal patches were discussed3.

6. Lucina , B. Lopes., et al .,. Have investigated the in vitro penetration and Transdermal delivery of vitamin K. they have incorporated the vitamin K with monoolein based liquid crystalline and shown the enhancement of skin penetration. They have demonstrated that the topical delivery of Vitamin K incorporated in a lipophilic vehicle and it is useful to increase the effectiveness of topical vitamin K therapy 10 .

7. Saxena M.,et al.,.Have studied Formulation and Evaluation of Transdermal patches of Metaclopramide Hydrochloride, The physiochemical parameters like Thickness, Weight variation , Moisture content, Moisture uptake and Drug permeation studies were evaluated for the preparation patches2.

8. Shahil Lewis.,et al .,, Have investigated Design and Evaluation of Matrix Type and Membrane Contrilled Transdermal Delivery Systems of nicotinic suitable for use in smoking cessation, invitro release studies of Transdermal patches were discussed4.

9. M.Bharkatiya,.,et al.,.Have Studied Designing and Evaluation of Propranolol Hydrochloride Transdermal Patches. The plot of cumulative percent permitted versus time, Higuchi plot and plot of log cumulative percent-retained Vs time 7 .

10. Ritesh Kumar., et al.,. Have studied patented active transport transdermal drug delivery technologies, It is expected to increase with successful development of new approaches capable of enhancing the skin permeability of drugs 9.

6.3 Objective of the study:

5 The present study aimed to formulate and evaluate the Transdermal Drug Delivery system. Most of the drugs are reported a risk of undesirable side effects when given orally. Since skin is an excellent barrier for drug transport the various therapeutic agents are administered as TDD for systemic effect. There are various chemical and physical methods to promote Transdermal drug permeation through the disruption of the skin barrier. The main challenge for many Transdermal formulations is to effectively increase the permeability of the active ingredient through the stratum corneum. while avoiding skin irritation12

Hence, investigation of anti diabetic drug like Glipizide of both therapeutic and prophylactic usage along with penetration enhancers is highly essential when subjected to Transdermal drug delivery system. Based on objective, the plan of work is as follows,

1. Selection of drug.

2. Preformulation studies.

3. Preparation of TDDS with different suitable polymers and other additives.

4. Physicochemical evaluation.

5. To study the invitro drug release

6. To study the in vivo skin permeation.

6 7. MATERIAL AND METHODS:

Material:

Drug : drug samples of ant diabetic drug.

Polymers : Hydroxy propyl methyl cellulose (HPMC), Polyvinylpyrrolidone, polyethylene glycol, cellulose derivatives etc.

Enhancers : selected enhaners like Dimethyl sulfoxide (DMSO), SLS, Sodium glycocholate etc. Diffusion cell : Diffusion cell models like Franz diffusion cell,

Reagents : The reagents, solvents and other excipients of analytical grade

Instruments : The PH meter, UV spectrophotometer, etc.

Method:

1. Preparation of monolithic matrix film or backing membrane: Method used for the preparation of film is by casting technique by using some selected polymers in an aluminum or glass dish.

2. Preparation of Drug containing film: Some selected compositions of known concentration polymers are dissolved in solvent and then known amount of drug dissolved under mild agitation. From this drug containing latex will be prepared in a dish.

7 7.1 Source of Data:

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. Transdermal drug delivery system shall prepare by using suitable methods.

7.2 Method of collection of data : a) Development of transdermal drug delivery system. b) Pre-forInulation study such as · Solubility · Partition coefficient · Calibration · Compatibility of drugs and other additives

c) Characterization study · uniformity of weight · tensile strength · folding endurance · percentage moisture absorption · percentage moisture loss · water vapour transmission rate · drug content etc., · In vitro diffusion study, using Diffusion cell models like Franz diffusion cell,  In vivo studies will be subjected to suitable animal spices

8 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. Yes, anti diabetic activity of transdermal drug delivery system will be carried out on Invivo models.

7.4 Has ethical clearance been obtained from your institution in case of 7.3? The study is cleared from Ethical committee of the institution.

601/02C/CPCSEA

Copy enclosed

8. LIST IF REFERENCE:

1. Hadgraft j, Lane ME. Skin permeation: The years of enlightenment. Int j pharm 2005;305:2-12

2. Saxena.M., Mutalik.S.and Reddy M.S, Formulation and Evaluation of Transdermal patches of Metoclopramide Hydrochloride,Indian drug.2006,43. (9),740-745.

3. Subal.C.Bsdsl, Transdermal patches :What Pharmacist Need to Know? The Pharma Review,2006,4(22),52.

4. Shaila.Lewis, S.Pandey and N.Udupa, Design and Evaluation of Matrix type and membrane controlled Transdermal Delivery Systems of Nicotin sutiable for using smoking cessation,IND.Journal.Pharm.Sci.,2006,68(2),179-184.

5. M.K.Das, A.Bhattacharya and S.K.Ghosal Transdermal Delivery System of Trazadone Hydrochloride from Acrylic films prepared from Aqueous extract,Ind.Journal .pharm.Sci.2006,68,41-46.

6. J. Bagya Lakshmi, Sheheera Sheriff, Sonia John, J.k. Ravi, P. K. Manna, R. Manavalan., “Transdermal Delivery of Ampicillin Sodium

9 Patch made from Volatile Vehicle” Ind. Journ. Pharm.Sci. Jan- Feb.2004, Vol.66, 103- 105.

7. M.Bharkatiya, R.k, Nema, G.d. Gupta, R.S. Guard. “Desiging and Evaluation of Propranolol Hydrochloride Transdermal patches”. THE PHARMA REVIEW, June 2005, Vol 3 (No. 16), 113.

8. Sadhana P.Gupta and S.K.Jain “Effective and Controlled Transdermal Delivery of Metoprolol Tartarate”. Ind. Jour. Pharm.Sci. May- June 2005, Vol. 67(No 3), 346- 350

9. Ritesh Kumar, Jashanjit Singh, Anil Philip and Kamla Pathak “Patented active transport transdermal drug delivery technologies”, THE PHARMA REVIEW, Feb 2007, Vol. 5 (No.26), 133

10. Luciana,B.Lopes.,Fernanda,F,F.Speretta.,M.Vitoria,L.B.Bently.,Enhancement of skin penetration of vitamin K using monolein-based liquid crystalline systems, European J.Pharm and Biopharm 2007,32,209-215.

11. Ponia Brijendra Singh., Choudhury Pratim Kumar., Penetration Enhancement for Transdermal Drug Delivery Systemic Agents, Journal of Pharm.Research 2007.6(2),44-50.

12. Transdermal Drug Delivery –Technologies, Markets and uptakes, Jain Pharmabiotech,2006,94.

13. N.K.Jain., Targeted delivery of drug., I st Edition, 452-462.

14. Goer.H.,Pharm.RES. 13., (12) 1996.P.1765.

10 15. Chein. Y.W. in controlled drug delivery fundamental and applications 2nd edition., Robinson.J.R., Vincent,H.L.L., Eds. Marcel dekker.inc., N.Y. (1987).P.523.

16. Bergstron.T.K.,Good.W.R.Fiesullin.S., Signur.C.J. Controlled release, 15 (1991), P.271.

17. Kandavilli S, Nair V Panchagnula.R. Polymers in transdermal drug delivery systems. Pharmaceutical Technology 2002;26(5):62- 80.

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

11.2 Signature:

11.3 Co-guide (if any ):

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 & The above-mentioned information is Principal: correct and I recommend the same for approval.

12.2 Signature:

12 From DETROJA PURUSHARTH M. 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 “DEVELOPMENT AND EVALUATION OF TRANSDERMAL DRUG DELIVERY SYSTEM CONTAINING ANTI DIABETIC DRUG” for registration in M.Pharm (Pharmaceutics) of Rajiv Gandhi University of Health Sciences, Banglore, Karnataka. Kindly accept the same and acknowledge. Thanking you,

Yours Faithfully,

(DETROJA PURUSHARTH M.)

Place: Channapatna Date : 10-11-2008

Guide: Mr. K.SENTHIL KUMAR M.Pharm, ASSISTANT 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