Design and Evaluation of Controlled Release Tablets of Venlafaxine Hydrochloride

DESIGN AND EVALUATION OF CONTROLLED RELEASE TABLETS OF VENLAFAXINE HYDROCHLORIDE

M. Pharm. Dissertation Protocol Submitted to the Rajiv Gandhi University of Health Sciences, Karnataka. Bangalore.

By PORWAL AMOL SHIVRATANJI B. Pharm.

Under the Guidance of P.RAVI PRAKASH, Assistant Professor, Dept. of Pharmaceutics.

DEPARTMENT OF PHARMACEUTICS N.E.T. PHARMACY COLLEGE, RAICHUR. 2007 Rajiv Gandhi University of Health Sciences, Karnataka Bangalore

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

PORWAL AMOL SHIVRATANJI 1 Name of candidate and address (In C/O DR MUNDADA CLINIC, Block Letters) JAMKAR COLONY, GAVANE ROAD, PARBHANI DIST-PARBHANI MAHARASHTRA

2 Name of the Institute N.E.T.PHARMACY COLLEGE, RAICHUR.

3 Course of study and subject: M.PHARM. PHARMACEUTICS.

4 Date of admission of course: 07-05-07

5 Title of the topic: DESIGN AND EVALUATION OF CONTROLLED RELEASE TABLETS OF VENLAFAXINE HYDROCHLORIDE

6 Brief Resume of this intended work: 6.1 Need for the study Enclosure-I 6.2 Review of Literature Enclosure-II 6.3 Objectives of study Enclosure-III

7 Materials and Methods: 7.1 Source of data Enclosure-IV 7.2 Method of collection of data (Including Sampling procedure, if any) Enclosure-V 7.3 Does the study require any investigation or interventions to be conducted on patients of humans or animals ? If so, please describe briefly. ------7.4 Has ethical clearance been obtained from your institution in case of 7.3 ? ------

8 List of References Enclosure-VI

9 Signature of the candidate

10 Remarks of the Guide The proposed work can be carried out in the laboratory

11 Name and designation of P.RAVI PRAKASH, (in block letters) Assistant Professor, 11.1 Guide Dept. of Pharmaceutics, N.E.T. Pharmacy college, RAICHUR- 584103.

11.2 Signature

11.3 Co-Guide (if any) ------

11.4 Signature ------

11.5 Head of Department PROF.H. DODDAYYA, Dept. of pharmaceutics, N.E.T. Pharmacy college, RAICHUR- 584103. 11.6 Signature

12 12.1 Remarks of the PROF. H. DODDAYYA, Chairman and Principal Principal, N. E. T. Pharmacy College, RAICHUR-584103.

12.2 Signature Enclosure-I

6) Brief resume of the intended work. 6.1) Need for the study: Oral route has been the commonly adapted and most convenient route for drug delivery because of more flexibility in the formulation, patient compliance and convenient for a physician during dose adjustment. The drugs are generally formulated in the conventional manner in immediate-release dosage forms. When conventional dosage forms are taken on schedule and more than once daily, leads to fluctuations in plasma drug concentration and doses may be missed. To overcome this, controlled release formulations have been designed. These have advantages such as reduced blood level fluctuations; reduction in dosing frequency, enhanced patient convenience and compliance, reduction in adverse side effects and reduction in overall health care costs.1 The common way of controlling delivery is incorporating drug into a

2-4 polymer . Matrix tablet can be formulated using hydrophilic and hydrophobic materials. Hydrophilic matrix systems are popular and versatile controlled release systems. Among the polysaccharides used to produce such systems, there are ranges of cellulose ethers e.g. HPMC, Sodium alginate, carrageenan, chitosan and xanthan gum 5-6 and guar gum. 7-9 1-[2-(Dimethylamino)-l-(p-methoxyphenyl)ethyl]cyclohexanol hydrochloride (Venlafaxine hydrochloride) is a oral antidepressant drug. Venlafaxine is readily absorbed from gastrointestinal tract. After oral dose it undergoes extensive first pass metabolism in the liver to the active metabolite O-desmethylvenlafaxine. Peak plasma concentration of venlafaxine and O-desmethylvenlafaxine appear about 2 and 4 hours after dose respectively. The protein binding of venlafaxine and O-desmethylvenlafaxine is low. The mean elimination half life of venlafaxine is 5 hours. 10 The usual dose is 75 mg daily with maximum of 375 mg. In present study Venlafaxine hydrochloride containing controlled release formulations will be developed and an attempt will be made to investigate the factors influencing release kinetics. Enclosure-II

6.2) Review of literature:

1) Jun HW et al. (2005)11 prepared controlled release matrix tablets of ibuprofen by direct compression using blends of cellulose ether and carrageenans and were reported to show successfully sustained release of ibuprofen for a period of 10-12 hours. 2) Pao – Chu Wu et al (2004)12 formulated once daily propranolol extended release tablet dosage form containing HPMC, methyl cellulose and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing polynominal equation were use to search for optimum formulation with specific release rate at different time interval. The result reported to be shown that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicate that the optimal formulation would be obtained using response surface methodology. 3) Hossein Zia et al. (2002)13 reported the formulation and optimization of sustained-release tablet of ketorolac tromethamine using hydroxy propyl methyl cellulose (HPMC) and sodium carboxy methyl cellulose in different ratio along with ethyl cellulose. It has been reported that the release mechanism was affected by the amount of drug, HPMC /NaCMC ratio, ethyl cellulose, three way interaction and two way interaction between drug and HPMC/NaCMC and EC and HPMC / NaCMC. Experimental design has been reported to give a direction for further optimization. 4) Eddy Castellanos Gil et al. (2006)14 has developed and optimized novel sustained-release dextran tablet formulation for propranolol HCL. The influence of matrix forming agents like native dextran and hydroxy propyl methyl cellulose (HPMC) with cetyl alcohol was investigated. A formulation with a dextran: HPMC ratio of 4:1(w/w) and 15%(w/w) cetyl alcohol were reported to be best sustained-release matrix tablet. 5) Nakhat PD et al. (2006)15 reported the design and evaluation of xanthan gum- based sustained-release matrix tablet of diclofenac sodium. It has been concluded that xantham gum used as an effective matrix former, to retard the release of diclofenac sodium for extended period of time. Enclosure-III

6.3) Objectives of the study: The present study is planned with the following objectives: 1) To prepare the controlled release tablet of venlafaxine hydrochloride using various polymers. 2) To evaluate the formulations with respect to various physical parameters (weight variation, hardness, friability, etc.) 3) To evaluate the tablets with respect to content uniformity and in vitro dissolution rate studies. 4) To carry out stability studies for tablets. Enclosure-IV

7) Materials and Methods: 7.1) Source of data: Primary data: This data will be collected by conducting laboratory experiments and recording the observation. Secondary data: This will be collected from various journals and textbooks.

Enclosure-V

7.2) Method of collection of data: The data for the study is planned to collect from the laboratory based experiments, which include the following - Preparation of controlled release tablet of venlafaxine hydrochloride using various polymers. Evaluation of matrix tablet with respect to drug content determination, in vitro dissolution rate studies etc. Conducting stability studies at different temperature and humidity conditions. Enclosure- VI 8) List of references: 1) Ansel HC; Allen.; Jr LV., Popovich NG; (Ed.). Modified release dosage forms and drug delivery systems. In: Pharmaceutical dosage forms and drug delivery systems. 7th Ed. Lippincott Williams and Wilkins. India, (2000); 229-243. 2) Narasimhan B; Mallapragada SK; Peppasin NA. in: E . Mathiowitz (Ed). Encyclopedia of Controlled Drug Delivery. John Wiley and Sons. New York. (1999); 921-935. 3) Langer R; Peppas NA. Chemical and Physical structure of polymers as carrier for controlled release of bioactive agent : A review, Macromol J. Sci, Rev. Macromol. Chem. (1983); C23(1) , 61-126. 4) Langer R. Polymeric delivery systems for controlled drug release. Chem. Eng. Commun. (1980); 6, 1-48. 5) Alderman DA. Review of cellulose ethers in hydrophilic matrices for oral controlled release dosage form. Int. J. Pharm. Technol. Prod. Mfr. (1984); 5, 1- 9. 6) Melia CD. Hydrophilic matrix sustained release system based on polysaccharide carriers. Crit. Rev. Ther. Drug Carrier Sys. (1991); 8(4), 395-421. 7) Sinha VR; Kumria R. Polysaccharide matrices for microbially triggered drug delivery to the colon. Drug Dev. Ind. Pharm. (2004); 30, 143-150. 8) Patra CN; Bhanoji rao ME; Yadav; Prakash K. Influence of some cellulose ethers on the release of propranolol HCl from guar gum matrix tablets. Indian J. Pharm. Sci. (2004); 66(5), 636-641. 9) Kale VV; Kasliwal RH; Avari JG. Effect of matrix geometry on drug release from guar gum matrix tablet. Indian Drugs. (2005); 42(2), 84-86. 10) Martindale; The Complete Drug Reference. 34th Edition. Pharmaceutical Press, Great Britain. (2005); 321-323. 11) Nerurkar J; Jun HW; Price JC; Park MO. Controlled-release matrix tablets of ibuprofen using cellulose ether and carrageenans: effect of formulation factors on dissolution rate. European J. Pharma and Biopharmaceutics. (2005); 61, 56- 68 12) Yaw-Bin Huang; Yi-Hung Tsai; Pao-chu Wn; Jui-Sheng Chang; Kozo Takayama. Once-daily propanolol extended release tablet dosage form : formulation design design and Invitro- Invivo investigation. European J.Pharma and Biopharmaceutics. (2004); 58, 607-614. 13) Vatsaraj N; Zia H; Needham T. Formulation and Optimization of a novel sustained-release dextran tablet formulation for propanolol hydrochloride. Taylor & Francis; health sciences. (2002); 9, 153-159. 14) Gil EC; Colarte AI; Bataille B; Pedraz JL; Rodriguez F; Heinamaki J. Development and Optimization of a novel sustained-release dextran tablet formulation for propanolol hydrochloride, Int. J. Pharm. (2006 ); 31, 732-39. 15) Yeole PG; Galgatte UC; Babla IB; Nakhat PD. Design and evaluation of Xanthan gum-based sustained release matrix tablet of diclofenac sodium, Indian J. Pharm. Sci. (2006); 68(2), 185-189.