Formulation and Evaluation of Cephalexin Extended-release Matrix Tablets Using Hydroxy Propyl Methyl Cellulose as Rate-controlling Polymer

Abstract

The present investigation reports the design and evaluation of six-hour extended release film-coated matrix tablets of cephalexin using different grades of hydrophilic polymer hydroxypropylmethylcellulose (HPMC) employing direct compression method. The formulation studies performed included the physical compatibility studies, Differential Scanning Calorimetry analysis, drug characterization using Fourier Transform Infra Red spectroscopic analysis and particle size analysis using sieve method. The tablets were evaluated for weight variation, hardness, thickness and friability. Results of the studies indicate that the polymers used have significant release-retarding effect on the formulation. The dissolution profile comparison of the prepared batches P1 to P8 and market preparation (Sporidex AF 375) was done by using Food and Drug Administration-recommended similarity factor (f₂) determination. The formulation P8 (10% HPMC K4M, 15% HPMC 15cps) with a similarity factor (f₂) of 77.75 was selected as the optimized formulae for scale-up batches. The dissolution data of the best formulation P8 was fitted into zero order, first order, Higuchi and Korsmeyer–Peppas models to identify the pharmacokinetics and mechanism of drug release. The results of the accelerated stability study of best formulation P8 for three months revealed that storage conditions were not found to have made any significant changes in final formulation F3. The release of cephalexin was prolonged for 6 h by using polymer combinations of HPMC and a twice daily matrix tablet was formulated.

Keywords: Cephalexin; differential scanning calorimetry; Fourier transform infra red spectroscopic; hydroxy propyl methyl cellulose; matrix tablets; release kinetics; similarity factor (f₂)