Formulation and In-Vitro Evaluation of Extended Release Matrix Tablets of Trimetazidine HCL

AIM:The aim of this study is to develop the extended release tablet of Trimetazidine HCL for the potential treatment of Angina Pectorise.REASONS FOR SELECTION OF TRIMETAZIDINE HCL: 1.Trimetazidine HCL (TMZ), the antianginal compound approved for clinical use is widely used for treatment of antianginal either alone or in combination with other antianginal agents.2. However, the main limitation to therapeutic effectiveness of TMZ is its dose-dependent hematological toxicity, low therapeutic index, short biological half-life, and poor bioavailability. 3.After oral administration, it is rapidly absorbed from the gastrointestinal tract (GIT) exhibiting a peak plasma concentration of 84 ng/ml at 1.8+/- .7 hrs hours. The biological half-life of TMZ is 6 hours, thus necessitating frequent administration (3 to 4 times a day) to maintain constant therapeutic drug levels.REASONS FOR SELECTION OF DOSAGE FORM:1.The goal of any drug delivery system is to provide a therapeutic amount of drug to the proper site in the body to promptly achieve and maintain the defined drug concentration.2.In pharmaceutical practice, drug administration to patient exists in several approaches, one of which is conventional, i.e. drug is given several times a day, to produce desired therapeutic effect.3.In pharmaceutical practice, drug administration to patient exists in several approaches, one of which is conventional, i.e. drug is given several times a day, to produce desired therapeutic effect.4.Hence the above potential problem can be minimized or reduced by formulating the drug in release control matrix i.e. sustain release system .This system minimizes or eliminates side effects, provide patient compliance, economically and promptly achieves and maintains the desired effect. Hence due to above properties, it may be more efficient to deliver the drug at a sustained manner, at a reduced input rate compared with oral conventional dose occurring from a conventional release dosage form Trimetazidine HCL is available in market, presently.THE MAIN OBJECTIVE OF PRESENT STUDY:1.The present study is to investigate the possibility of developing extended release dosage form for the drug Trimetazidine Hcl by using combined polymers i.e. HPMC k15CR with Ethyl cellulose, Metalose (Hypermellose) with Ethyl cellulose, HPMC k15CR with Metalose and Etyl Cellulose in different ratios as matrix. 2.It can be achieved by planning for trails until the desired release pattern is obtained. The aim is to evaluate the release profile of drug from fabricated extended release matrix tablets.SUMMARY AND CONCLUSION:O ral route of drug administration is oldest and safest mode of drug administration. It posses several advantages. It provides accurate dosing without assistantship of administration. In conventional oral drug delivery system, there is little or no control over release of drug, and effective concentration at the target site can be achieved by administration of grossly excessive dosage form. Sustained release technology is relatively new field and as a consequence, research in the field has been extremely fertile and has produced many discoveries. With many drugs, the basic goal is to achieve a steady state blood level that is therapeutically effective and non-toxic for an extended period of time. The design of proper dosage form is an important element to accomplish this goal. Trimetazidine HCL is Vasodilator with half life of 6 hours and requires multiple daily doses to maintain adequate plasma concentrations. So it is selected to prepare an extended release Matrix tablet. The objective of this present study is to develop an extended release Matrix tablet of Trimetazidine HCL which releases the drug in an extended manner over a period of 8 hours, by using different polymers and study on polymer concentration effect on release pattern. T he present study was undertaken with an aim to formulate develop and evaluate Trimetazidine HCL extended release matrix tablets using different polymers as release retarding agent. Preformulation study was done initially and results directed for the further course of formulation. Based on Preformulation studies different batches of Trimetazidine HCL were prepared using selected excipients. Powders were evaluated for tests Angle of repose, Bulk density, tapped density, compressibility index, and Hausner ratio before being punched as tablets. IR spectra studies revealed that the drug and polymers used were compatible.Various formulations of sustained release matrix tablets of Trimetazidine HCL were developed using various polymers viz, HPMC K-15CR, Hypermellose, Ethyl Cellulose in different proportions and combinations by Wet Granulation technique. The tablets were evaluated for physical characterization, in vitro swelling behavior, in vitro release study and stability studies. Observations of all formulations for physical characterization had shown that, all of them comply with the specifications of official pharmacopoeias and/or standard references. Results of in vitro release profile indicated that formulation F9 was the most promising formulation as the extent of drug release from this formulation was high as compared to other formulations. Results of in-vitro swelling study indicate that the formulation F9 was having considerable swelling index. S t a bility study was conducted on tablets of Batch F9 stored at 300C (Room Temperature) and 400C for one month. Tablets were evaluated for hardness, friability, invitro release profile and drug content. After one month no significant changes were observed in any of the studied parameters during the study period, thus it could be concluded that formulation was stable. It was concluded that the tablets of batch F9 had considerable swelling behaviors and in vitro drug release. Percentage drug release in 8 hr is 80.77. It was observed that tablets of batch F9 followed the Huguchi release profiles. From the above results and discussion it is concluded that formulation of Extended release matrix tablet of Trimetazidine HCL containing HPMC K-15 (19.44%) and Hypermellose (19.44%), Ethyl cellulose (19.44%) batch F9 can be taken as an ideal or optimized formulation Extended release matrix tablet for 8 hour release as it fulfills the requirements for extended release matrix tablet