“FORMULATION AND EVALUATION OF OSMOTICALLY CONTROLLED

DRUG DELIVERY SYSTEM OF ANTI−DIABETIC DRUG”

DISSERTATION PROTOCOL

Submitted to the

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES,BANGALORE, KARNATAKA.

BY

BANUPRAKASH S M

M.Pharm, Part- I

DEPARTMENT OF PHARMACEUTICS.

UNDERTHEGUIDANCE OF

Dr.SUNIL KUMAR AGARWAL Ph.D

PROFESSOR

DEPARTMENT OF PHARMACEUTICS

PriyadarshiniCollege of Pharmacy,

Koratagere Tumkur-572129

2012

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

Annexure – II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name of the candidate andaddress /

Mr.BANUPRAKASH S M

DEPARTMENT OF pharmaceutics
PRIYADARSHINI COLLEGE OF PHARMACY
KORATAGERE TUMKUR – 562129.
KARNATAKA.
2. /

Name of the institution

/ .PRIYADARSHINI COLLEGE OF PHARMACY
KORATAGERE TUMKUR – 562129.
KARNATAKA.
3. /

Course of study & subject

/ MASTER OF PHARMACY IN pharmaceutics.
4. /

Date of admission to course

/ 16-11-2012
5. /

Title of the topic

“FORMULATION AND EVALUATION OF OSMOTICALLY CONTROLLED DRUG DELIVERY SYSTEM OF
ANTI−DIABETIC DRUG”
6. Brief resume of the intended work:

6.1 Need for the study:

Osmotically controlled oral drug delivery systems (OCODDS) utilize osmotic pressure as energy source for the controlled delivery of drugs. Osmosis¹⁻³ is an aristocratic biophenomenon which is exploited for development of delivery systems with every desirable properties of an ideal controlled drug delivery systems.

Present study is aimed towards the development of extended release formulation of antidiabetic drug (i.e. Glimepiride)4 based on osmotic technology. In this study, two-layer push-pull osmotic tablet system5-6 is developed.

Antidiabetic drug which is important for the treatment of hypoglycemic disorders. Antidiabetic drug like Glimepiride7-8 has a relatively short elimination half life (5 h).Thereby requiring twice daily dosing in large number of patients, which often leads to non-compliance. There is a strong clinical need and market potential for a new drug delivery system.

Advantages of OCODDS :

  1. It is independent of pΗ and other physiological parameters to a large extent.
  2. Reduce side effects.
  3. Improve patient compliance.
  4. Decrease dosing frequency.
  5. Easy to formulate and simple in operation.
  6. Sustained and consistent blood levels within blood.

6.2 Review of Literature:

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.Vyas et al.⁸ studied on oral osmotic system which can deliver theophylline andsalbutamol sulphate simultaneously for extended period of time. A modified two layered,push-pull osmotic system was developed.

2.Gan et al.⁹ developed glipizide osmotic pump tablets by using PEG4000 and cellulose acetate.

3.Garg et al.¹⁰ developed extended release formulation of glipizide based on osmotic technology and evaluated.

4.Vyas et al.¹¹ developed Diltiazem HCL osmotic pump.

5.Ozdemir et al.¹² design of ibuprofen osmotic pumps. It was observed that the release rate of ibuprofen was influenced by the concentration of osmotic agents NaCl and PEG 6000.

6.Rani et al.¹³ prepared and compared evaluation of fabricated matrix, osmotic matrix, and osmotic pump tablets for controlled delivery of Diclofenac sodium.

7.Rani et al.¹⁴ developed and evaluated an osmotic pump osmotic pump tablets of diclofenac sodium. Effects of orifice size, coating membrane type, coating thickness were studied.

8.Ramakrishna et al.¹⁵ compared the performance ofcellulose acetate and ethylcellulose –HPMC combination coatings as semipermeable membranes for osmotic pump tablets of naproxen sodium.

9.Ouyang et al.¹⁶ prepared simple elementary osmotic pump system that could deliver Metformin HCL and Glimepiride simultaneously for extended period of time.

10.Yan et al.¹⁷ prepared pulsed-release system based on bilayer coated tablets containing an osmotically active agent is prepared. HPMC and the mixture of Eudragit RS and RL were applied as the swelling layer and semi-permeable outer coat respectively.

11.Mahalakshmi R.et al.18 developed Extended release controlled porosity osmotic pump formulations of model drug glipizide were developed using awicking agent and asolubilizing agent.

12.Kumar Guarve et al.¹⁹ designed a controlled porosity osmotic pump capsule of Carve-dilol which contains pore-forming water soluble additives. Cellulose acetate wasused as the semi-permeable membrane.

6.3 Objectives of the Study:

The objectives of proposed study are:

  1. To formulate bilayer push-pull osmotic tablets of antidiabetic drug using different excipients like carbopol 934P, psyllum husk powder, cellulose acetate, mannitol, PVP K30, NaCl, Mg.stearate, microcrystalline cellulose, talc, 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.
  4. To perform In-vitro dissolution studies.

5. To perform the stability studies.

7. Materials and Methods:

Materials:-

1)Drug: Antidiabetic (i.e.Glimepiride)

2)Ingredients: carbopol 934P, psyllum husk powder, PVP K30, MCC, cellulose acetate, NaCl, Mg.stearate, mannitol, HCl, talc, etc.

3)Method:(any of the below mentioned suitable methods)

  • Wet granulation
  • Dry granulation
  • Direct compression method.

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 investigationat Pharmaceutics Department Laboratory of Dr. HLTCP and recording observation. Osmotic tablet shall prepare by using suitable methods.

7.2Method of collection of data : (Including sampling procedure, if any)

Bi-layer push-pull osmotic tablets will be prepared by using carbopol 934 P, psyllum husk powder, PVP K30, MCC, cellulose acetate, NaCl, Mg.stearate, mannitol, talc, etc.

  1. The analytical method for the drug shall be developed and validated using UV-Spectrophotometer (UV-1700 SHIMADZU, JAPAN).
  1. The formulation will be evaluated for pre-compression characteristics like Bulk Density, Tapped Density, Angle of Repose, and Carr’s Index.
  1. Compression characteristic and In-Vitro dissolution studies will be carried out in the USP Dissolution Apparatus (DISSO 2000, LAB INDIA).
  1. To perform the stability studies as per ICH guidelines.

7.3Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.

-- Not Applicable --

7.4 Has ethical clearance been obtained from your institution in case of 7.3 ?

-- Not Applicable --

8. List of References:

  1. S.P.Vyas and R.K.Khar, “Controlled drug delivery concepts and advances” osmotically regulated systems, first edition, 477-501.
  2. Rajan K. Verma ,Sanjay Garg, “Formulation aspects in the development of osmotically controlled oral drug delivery system” , Journal of Controlled Release, 79(2002)7-27.
  3. Jain N.K., “Advances in Novel and Controlled Delivery”, first edition (1997), 18-39.
  4. Goodman and Gilman “The Pharmacological Basis of Therapeutics” 11th edition, 1635-1638, 2006.
  5. British Pharmacopoeia 2008 vol.1, 1000.
  6. Indian Pharmacopoeia 2010 vol.2, 1418-1420.
  7. D. Prabhakaran ,Paramjitsingh, Parijat Kanaujia, K.S.Jaganathan, Amit ravat, Suresh P Vyas, “Modified push-pull osmotic system for simultaneous delivery of theophylline and salbutamol : development and in-vitro characterization”, International Journal of Pharmaceutics, 284(2004)95-108.
  8. Yong Gan , Weisan Pan, Mingchun Wei, Ruhua Zhang, “Cyclodextrin complex osmotic tablet for glipizide delivery” Drug development and industrial pharmacy, Vol.28(2003)342-348.
  9. Rajan K Verma, Sanjay Garg, “Development and evaluation of osmotically controlled oral drug delivery system of Glipizide”, European Journal of Pharmaceutics and Biopharmaceutics, 57(2004) 513-525.
  10. D. Prabhakaran, Paramjitsingh, Parijat Kanaujia, K.S, Suresh P Vyas, “Effect of hydrophilic polymers on the release of diltiazem HCl from elementary osmotic pumps”, International Journal of Pharmaceutics, 259(2003)173-179.
  11. Nurten Ozdemir, Jfilide Sahin, “Design of a controlled release osmotic system for ibuprofen”, International Journal of Pharmaceutics, 158(1997)91-97.
  12. Mina Rani and Brahmeshwar Mishra, “Comparative in-vitro and in-vivo evaluation of matrix, osmotic matrix, and osmotic pump tablets for controlled drug delivery of diclofenac sodium”, AAPS PharmaSciTech, 2004;5(4) Article 71.
  13. Mina Rani and Rahul Surana, “Development and biopharmaceutical evaluation of osmotic pump tablets for controlled delivery of diclofenac sodium” Acta Pharm, 53(2003) 263-273.
  14. N.Ramakrishna, B.Mishra, , “ Plasticizer Effect and Comparative Evaluation of Cellulose Acetate and Ethylcellulose-HPMC Combination Coatings as Semipermeable Membranes for Oral Osmotic Pumps of Naproxen Sodium”, Drug Development and Industrial Pharmacy, vol.28.no.4,(2002)403-412.
  15. Ouyang D, Nie S, Li W, Guo H, Liu H, Pan V, “ Design and Evaluation of Compound Metformin/Glipizide Elementary Osmotic Tablets.”, J Pharm Pharmacol.2005 jul;57(7):817-820.
  16. Yan Zhang, Zhirong Zhang, Fang Wu, “ A novel pulsed-release system based on swelling and osmotic pumping mechanism”, Journal of Controlled Release, Vol.89, issue 1, 14th April,2003,47-55.
  17. Mahalaxmi.R, Phanidhar Sastri, Ravikumar, Atin Kalra, Pritam Kanagale.D , Narkhede R.
  18. “ Enhancement of Dissolution of Glipizide from Controlled Porosity Osmotic Pump Using A Wicking Agent And A Solubilizing Agent” International Journal Of PharmatechResearch, Vol.1, No.3, 705-711, july-sep 2009.
  19. Kumar Guarve, G.D.Gupta “ Development of In-vitro Evaluation of OsmoticallyControlled Oral Drug Delivery System Of Carvedilol” , International Journal of Pharmaceutical Science and Drug Research, 2009; 1(2):80-82.
  20. Sahu Mnoranjan. Formulation of dual component drug delivery of Glimepiride and Metformin, Hydrochloride for immediate and sustained release.IJRAP, 2010; 1(2):624-633.
  21. Hindustan Abdul Ahad, Sreeramulu.J. Design and evaluation of sustained release matrix tabletsof Glimepiride based on combination of natural and synthetic polymers.IJABPT, 2010;1(3): 770-777.

9. /

Signature of candidate

10. /

Remark of the guides

The above given information is true and this work will be done under my guidance.

11. / Name & Designation of
(in block letters)
11.1 Guide / Dr.SUNIL KUMAR AGARWAL Ph.D
PROFESSOR,
DEPARTMENT OF PHARMACEUTICS PRIYADARSHINI COLLEGE OF PHARMACY
KORATAGERE TUMKUR – 562129.
KARNATAKA.
11.2 Signature
11.3 Co-guide (if any)
11.4 Signature
11.5 Head of the Department / Dr.SUNIL KUMAR AGARWAL Ph.D
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
PRIYADARSHINICOLLEGE OF PHARMACY,
KORATAGERE TUMKUR-572129 KARNATAKA.
11.6 Signature
12. / 12.1Remarks of the Chairman & Principal / The above-mentioned information is correct and I recommend the same for approval.
12.2 Signature

1