<p> FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF ACECLOFENAC USING COMBINATION OF NATURAL AND SYNTHETIC POLYMERS.</p><p>M.Pharm. Dissertation Protocol SUBMITTED TO THE Rajiv Gandhi University of Health Sciences, Karnataka Bangalore.</p><p>By SRINIDHI .T</p><p>B.Pharm.</p><p>Under the guidance of Prof. P S MINHAS M.Pharm, (Ph D)</p><p>DEPARTMENT OF PHARMACEUTICS, PRIYADARSHINI COLLEGE OF PHARMACY , KORATAGERE. 2011-2012 2</p><p>Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.</p><p>ANNEXURE II PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION SRINIDHI .T S/o THIMMAPPA .T, 1 PLOT NO.37, KIADB, KELAGOTE Name of candidate and address INDUSTRIAL AREA, (In Block Letters) CHITRADURGA - 577501</p><p>2 Name of the Institute Priyadarshini College Of Pharmacy, Kortagere.</p><p>3 Course of study and subject: M.Pharm. Pharmaceutics.</p><p>4 Date of admission of course: December’2011</p><p>5 Title of the topic: </p><p>" Formulation And Evaluation Of Sustained Release Matrix Tablets Of Aceclofenac Using Combination Of Natural And Synthetic Polymers."</p><p>6 Brief Resume of this intended work:</p><p>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. ------NO------7.4 Has ethical clearance been obtained from your institution in case of 7.3? ------NOT APPLICABLE------</p><p>8 List of References Enclosure-VI</p><p>9 Signature of the candidate</p><p>10 Remarks of the Guide The proposed work can be carried out in the laboratory</p><p>2 3</p><p>11 Name and designation of (In block letters) 11.1 Guide Prof. P S MINHAS Dept. of Pharmaceutics. Priyadarshini College of Pharmacy.</p><p>11.2 Signature</p><p>11.3 Co-Guide (if any) ------</p><p>11.4 Signature ------</p><p>11.5 Head of Department Prof. P S MINHAS Dept. of Pharmaceutics. Priyadarshini College of Pharmacy.</p><p>11.6 Signature</p><p>12 12.1 Remarks of the Chairman and Principal Prof. P S MINHAS Dept. of Pharmaceutics. Priyadarshini College of Pharmacy.</p><p>12.2 Signature</p><p>3 4</p><p>6) Brief resume of the intended work. 6.1) Need for the study: </p><p>Non steroidal anti-inflammatory drugs (NSAIDs) are considered to be the first line drugs in the symptomatic treatment of rheumatoid arthritis, osteoarthritis and spondylitis, Aceclofenac is one of them. It is a newer derivative of Diclofenac with low gastrointestinal complications. The short biological half‐life (3‐ 4h) and dosing frequency more than one per day make Aceclofenac an ideal candidate for sustained release. To reduce the frequency of administration and to improve patient compliance, a once‐daily sustained release formulation of Aceclofenac is desirable. Matrix tablets composed of drug and polymer as release retarding material offer the simplest approach in designing a sustained release system.[1,2]</p><p>Hydrophilic polymers are becoming very popular in formulating oral controlled-release tablets. As the dissolution medium or biological fluid penetrates the dosage form, the polymer material swells and drug molecules begin to move out of the system by diffusion at a determined rate by the nature and composition of the polymer as well as formulation type. [3, 4, 5, 6] </p><p>The use of naturally occurring hydrophilic biocompatible polymeric materials has been focused in recent research activity in the design of dosage form for oral controlled-release of drugs compare to synthetic polymers. The use of matrix devices to control the release of a variety of therapeutic agents has become very important in the development of controlled release dosage forms. The hydrophilic natural gums hydrate and swell on contact with water and these have been used for the preparation of single unit dosage forms. Also, the natural gums selected have an economic importance in being cheaper than many processed synthetic gums available. Biodegradability of synthetic polymers is questionable when compared with natural polymers. [4, 7, 8, 9]</p><p>Aloe vera has been used for medicinal purposes in several cultures for millennia: Greece, Egypt, India, Mexico, Japan and China. Egyptian queens Nefertiti and Cleopatra used it as part of their regular beauty regimes. Alexander the Great,</p><p>4 5 and Christopher Columbus used it to treat soldiers' wounds. The first reference to Aloe vera in English was a translation by John Goodyew in A.D. 1655 of Dioscorides' Medical treatise De Materia Medica. By the early 1800s, Aloe vera was in use as a laxative in the United States, but in the mid-1930s, a turning point occurred when it was successfully used to treat chronic and severe radiation dermatitis.[10]</p><p>In this research work the mucilage of aloe vera is used as polymer for sustained release tablets formulation as it is proved to be a very good excipient in sustained release tablets formulation.[11,12]</p><p>So aloe vera mucilage has anti- inflammatory, analgesic, wound healing and antiseptic properties which help in the aceclofenac actions also has anti - ulcer property which reduces gastric irritation caused by aceclofenac so it becomes the rationale behind this study to use aloe vera mucilage as polymer along with synthetic polymer.[10]</p><p>5 6</p><p>6.2) Review of literature: 1. Prajapathi sk,et al., In present study, an attempt has been made to evaluate the effect of natural gums on the release profile of drug from matrix system for once daily sustained release tablets formulations. Aceclofenac NSAIDs was used as a model drug to evaluate it release characteristics from different matrices. Matrix tablets of Aceclofenac were prepared by direct compression process using natural gums (xanthan gum and karaya gum) in different ratios drug: gum ratios of FX, FK and FXK (FX and FK in 1:1 ratio). The FXK matrices show prices controlled release than FX and FK matrices because of burst effect and fast release in case of FX and FK matrices respectively and there was no chemical interaction between drug and polymers in FXK formulation as confirmed by FTIR studies.[13] 2. Afsar C. et al., The objective of the present study was to develop “once daily” sustained release tablets of Aceclofenac (200mg) by wet granulation using hydrophilic polymer like Hydroxy propyl methyl cellulose K ‐100. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, invitro drug release, kinetic studies and stability studies. FTIR studies shown there was no interaction between drug and polymer.[14] 3. Subramaniam Kannan , et al., The objective of the present study was to develop “once daily”sustained release tablets of Aceclofenac (200mg) by wet granulation using hydrophilic polymer like Hydroxy propyl methyl cellulose K -100. The drug excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical studies, in- vitro drug release, kinetic studies and stability studies. FTIR studies shown there was no interaction between drug and polymer.[15] 4. Hindustan Abdul Ahad1, et al, The present research work was aimed to develop matrix tablets of Gliquidone with Aloe barbadensis miller leaves mucilage and Povidone and to study its functionality as a matrix forming agent for sustained release tablet formulations. Physicochemical properties of dried powdered mucilage of Aloe barbadensis miller mucilage and Povidone tablet blend were studied. Various formulations of Gliquidone Aloe barbadensis miller mucilage and Povidone were prepared. They found to have better satisfactory physicochemical</p><p>6 7</p><p> properties with low SD values. The swelling behavior and release rate characteristics were studied. The dissolution study proved that the dried Aloe barbadensis miller mucilage and Povidone combination can be used as a matrix forming material for making Sustained release matrix tablets.[16] 5. Girish K. Jani, et al., Evaluating Mucilage from Aloe Barbadensis Miller as a Pharmaceutical Excipient for Sustained-Release Matrix Tablets. Natural gums and mucilage have been widely explored as pharmaceutical excipients. The goal of this study was to extract mucilage from the leaves of Aloe barbadensis Miller and to study its functionality as an excipient in pharmaceutical sustained-release tablet formulations.[11] 6. Rajendra Kotadiya et al conducted a study on comparative evaluation study of matrix properties of natural gums and semi-synthetic all the formulations showed compliance with pharmacopoeial standards. A significant difference in release pattern was observed between the formulation F1, F2, F3, F4 and F5. F1, F3 and F5 release almost ~9% compare to initial burst effect of ~31% for F4 and F2 after 1h of dissolution period. At the end of 8 h of dissolution period it was found that 71.36%, 85.91%, 96.98%, 68.76% and 45.5% of drug release for F2, F4, F5, F3 and F1, respectively. Conclusions: Thus, natural gums show granulation and tablet properties that are similar to those of the extensively investigated hydrophilic matrices, HPMC. This suggests that the natural gums may be an ideal candidate in the formulation of matrix tablets on controlled drug delivery.[17] 7. Rajesh K S conducted study on Effect of hydrophilic Natural gums in formulation of oral-controlled release matrix Tablets of Propranolol hydrochloride The tablets with XLBG resulted in more uniform controlled drug release matrices than X and LBG, due to the utilization of the synergistic interaction of two biopolymers to produce a strong and elastic gel in the presence of a ternary component to control the drug release process and the smallest average size of the particles.[18] 8. Indranil Kumar Yadav et al conducetd study on Formulation, Evaluation and optimization of Aceclofenac sustained release matrix tablets. Formulation was stable at accelerated conditions of temperature and humidity. Results of the present study demonstrated that both hydrophilic and hydrophobic polymers and their combination could be successfully employed for formulating sustained release matrix tablets of Aceclofenac. The sustained release tablets can be expected to reduce the frequency of administration and decrease the dose</p><p>7 8</p><p> dependent side effects associated with repeated administration of conventional Aceclofenac.[19]</p><p>6.3) OBJECTIVE OF THE STUDY: 1. To carry out the Extraction of Mucilage from Aloe Vera. 2. To prepare sustained release matrix tablets using combination of natural and synthetic polymers. 3. To carry out preformulation studies for possible drug- polymer interaction. 4. To evaluate the tablets for properties and release profiles. 5. To carry out short term stability studies.</p><p>7) MATERIALS AND METHOD:</p><p>Materials:</p><p>Drug : Aceclofenac. Polymer : Various suitable grades of Hydroxy Propyl Methyl Cellulose (HPMC) & Natural polymer Such as aloe vera mucilage. Excipients : Suitable Binders, Granulating Vehicle, Lubricants, Glidants Etc.</p><p>Method: Development of Sustained release matrix tablets using Direct compression or wet granulation method.</p><p>Equipments: 1. UV spectrophotometer 2. Monsanto hardness tester 3. Roche friabilator 4. Electronic balance 5. Digital pH meter 6. Single pan digital balance 7. Tablet punching machine 8. Hot air oven 9. Dissolution test apparatus. 10. Stability chamber</p><p>8 9</p><p>11. FTIR spectrophotometer & DSC. Stability chamber</p><p>7.1) SOURCE OF DATA:</p><p>Review of Literature from:  Journals: such as - International Journal of Pharmaceutical Sciences. - International journal of Biopharmaceutics. - International Journal of Research in Pharmaceutical and Biomedical Sciences. - Indian Journal of Pharmaceutical Sciences. - Journal of Pharmacy Research. - Asian journal of pharmaceutical science.</p><p> Text book : Tripathi.K.D, Essentials of medical pharmacology Brahmankar DM and Jaiswal SB. Biopharmaceutics and Pharmacokinetics- A Treatise.</p><p> Internet Browsing.</p><p> J-gate @ Helinet.</p><p> Priyadarshini College Library.</p><p>7.2 METHOD OF COLLECTION OF DATA: The steps that will be followed are: 1. preformulation studies for drug polymer interaction. 2. Formulation of Sustained release matrix tablets using different approaches. 3. Selection of suitable optimized formula for the above mentioned preparation 4. Evaluation of the above formulation for  Thickness  Hardness</p><p>9 10</p><p> Friability  Weight variation  Disintegration time  Drug content  In-Vitro release profiles  Short term stability studies.</p><p>7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, please describe briefly ------NOT APLLICABLE ------</p><p>7.4 Has ethical clearance been obtained from your institution in case of 7.3. ----- NOT APPLICABLE-----</p><p>10 11</p><p>8) LIST OF REFERANCE:</p><p>1. Tripathi.K.D, Essentials of medical pharmacology, J.P. Publication, 6th Edition, 2009, 184-195. 2. Goodrich BF. Controlled Release Tablets and Capsules. Bulletin no. 17, Brecksville OH. Ed 1995. 3. Brahmankar DM and Jaiswal SB. Biopharmaceutics and Pharmacokinetics- A Treatise. Vallabh Prakashan. 1995; 1: 345-47. 4. Girish K Jani, Dhiren P Shah. Gum and mucilages: versatile excipients for pharmaceutical formulations. Asian journal of pharmaceutical science. 2009; 4(5):309-323. 5. KS Rajesh, MP Venkataraju and DV Gowda. Effect of hydrophilic natural gums in formulation of oral-controlled release matrix tablets of propranolol hydrochloride. Pak. J. Pharm. Sci. 2009; 22: 211-219. 6. D. F. Durso. Handbook of Water Soluble Gums and Resins. New York, NY: McGraw Hill, Kingsport Press. 1980; 12: 258-272. 7. A. Desai, S. Shidhaye, S. Malke. Use of natural release retardant in drug delivery system. Indian Drugs. 2005; 42: 565-575. 8. Sunil Kamboj, G D Gupta, Jagmohan Oberoy. Matrix Tablets: An Important Tool for Oral Controlled-Release Dosage Forms. Drug Dev Ind Pharm. 2009; (7) 6: 88-110. 9. Khullar P, Khar RK, Agarwal SP. Evaluation of guar gum in the preparation of sustained-release matrix tablets. Drug Dev Ind Pharm. 1998; 24: 1095-9. 10. Surjushe A, Vasani R, Saple DG. Aloe vera: A short review. Indian J Dermatol. 2008; 53:163-6. 11. Girish K. Jani, Dhiren P. Shah, Vineet C. Jain, Manish J. Patel, Disha A. Vithalani., Evaluating Mucilage from Aloe Barbadensis Miller as a Pharmaceutical Excipient for Sustained-Release Matrix Tablets, Nov 2, 2007, Pharmaceutical Technology(pharmatech.com/article).</p><p>11 12</p><p>12. S.K. Baveja, K.V. Rao, and J. Arora, "Examination of Natural Gums and Mucilages as Sustaining Agents in Tablet Dosage Forms," Indian J. Pharm. Sci. 50 (2), 89–92 (1988).Baveja SK, Rao KV and Arora J,"Examination of Natural Gums and Mucilages as Sustaining Agents in Tablet Dosage Forms," Indian J. Pharm. Sci. 1988, 50 (2); 89–92. 13. Prajapati SK, Richhaiya R, Singh VK, Singh AK, Kumar S, Chaudhary RK, Formulation And Evaluation Of Once Daily Sustained Release Matrix Tablet Of Aceclofenac Using Natural Gums. Journal of Drug Delivery & Therapeutics; 2012, 2(1) 16. 14. Afsar C. Shaikh, Sayyed Nazim, Shaikh Siraj, Tarique Khan, M. Siddik Patel, Mohammad Zameeruddin, Arshad Shaikh, Formulation And Evaluation Of Sustained Release Tablets Of Aceclofenac Using Hydrophilic Matrix System Int J Pharm Pharm Sci, Vol 3, Issue 2, 2011, 145148. 15. Subramaniam Kannan, Rangasamy Manivannan, Kugalur Ganesan Parthiban Kakkatummal Nishad And Natesan Senthil Kumar., Formulation And Evaluation Of Sustained Release Tablets Of Aceclofenac Using Hydrophilic Matrix System Int.J. Pharmtech Res.2010,2(3). 16. Hindustan Abdul Ahad, Chitta Suresh Kumar, Kishore Kumar Reddy B, Anil Kumar B, Chandra Sekhar A, Sushma K, Sairam T, Sivaji S. Preparation and evaluation of sustained release matrix tablets of gliquidone based on combination of natural and synthetic polymers, Journal of Advanced Pharmaceutical Research 2010, 1(2), 108-114. 17. Rajendra Kotadiya, Vishnu Patel, Harsha patel. Comparative evaluation study of matrix properties of natural gums and semi-synthetic polymer. Journal of Pharmacy Research Vol.1.Issue 2.Oct-December 2008. 18. Rajesh K S. et.al., Effect of hydrophilic Natural gums in formulation of oral- controlled release matrix Tablets of Propranolol hydrochloride Pak. J. Pharm. Sci., Vol.22, No.2, April 2009, pp.211-219. 19. Indranil Kumar Yadav, Hari Pratap Singh. et al., Formulation, evaluation and optimization of aceclofenac sustained release matrix tablets International Journal of PharmTech Research ISSN : 0974-4304 Vol.2, No.1, pp 592-598.</p><p>12</p>