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ABSTRACT:
The present investigation was to develop immediate release (IR) tablet formulations of Capecitabine an anti-cancer drug, using Hydroxy Propyl Methyl Cellulose (HPMC E5) as binding agent. The tablets were prepared by wet granulation process and evaluated for various physico-chemical/mechanical parameters. Among the formulations the optimised formulation was identified by comparing dissolution profiles with innovator. The formulation containing 97.5mg MCC (Avicel PH 101) as filler and 20mg HPMC E5 as binder gave a bioequivalent dissolution profile as innovator over a period of 60min (100.8 %). The dissolution data of optimized formulation was also evaluated for drug release kinetics and mechanisms. The significant factor for optimised formulation and innovator was evaluated.
KEYWORDS: Immediate release (IR) tablets; Capecitabine (API); HPMC; MCC and Significant factor.
INTRODUCTION:
The goal of any drug delivery system is to provide a therapeutic amount of drug to proper site in the body to achieve promptly and then to maintain the desired drug concentration. That is, the drug delivery system should deliver drug at a rate dedicated by the needs of the body over a specified period of treatment. Immediate-Release [IR] Preparations are primarily intended to achieve faster onset of action for drugs such as analgesics, antipyretics, and coronary vasodilators. Other advantages include enhanced oral bioavailability through transmucosal delivery and pregastric absorption, convenience in drug administration to dysphasic patients, especially the elderly and bedridden, and new business opportunities.
Capecitabine is orally administred chemotherapeutic agent used in the treatment of metastatic breast cancer and metastatic colorectal cancer. It is an oral systemic prodrug that is enzymatically converted to 5-fluorouracil (5-FU). Healthy and tumor cells metabolize 5-FU to 5-fluoro-2- deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, they inhibit the formation of thymidine triphosphate, which is essential for the synthesis of DNA. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP during the synthesis of RNA.
This metabolic error can interfere with RNA processing and protein synthesis. Presently, CPC is marketed as immediate release (IR) tablets (150, 500mg) which are at high cost. The present study is to formulate cost efficient product which is bioequivalent to innovator product.
MATERIALS AND METHODS:
Capecitabine (Natco Pharma Ltd, Hyderabad), Micro crystalline cellulose (FMC Bio polymers, New York), HPMC E5...