Formulation Design and Optimization of Hydrophilic Matrix Based Sustained Release Tablet of Clarithromycin Using a Design of Experiment (DoE)

Abstract

A well-defined and strictly controlled dissolution rate plays vital role in optimization of sustained release dosage form. For this purpose, a computer optimized technique, based on a response surface methodology (RSM) utilizing a quadratic equation and factorial design has been widely used for designing and optimization of different pharmaceutical formulations, which requires smaller number of experimental runs and is less time consuming than conventional formulation methods. The aim of the present study was to design and evaluate once daily sustained release clarithromycin tablet, using two molecular weight grades hydrophilic polymers, i.e. Methocel® K15M CR and Methocel® K100M CR as release retarding materials, utilizing a Design of Experiment (DoE) approach. The tablets were manufactured by response surface methodology based on 32 full factorial design utilizing a polynomial equation where both polymers used as independent variables, along with other requisite excipients. The cumulative percentages of drug released at 2, 12 and 24 hr were selected as dependent variables and restricted to 0-20%, 45-70%, and 80-100%, respectively. Regression and response surface analyses were performed using Design ExpertÒ software and found that the release pattern of clarithromycin from the matrix followed non-linear model at 2 and 12hrs but at 24hrs, the pattern was linear. From the overlay plot, one of among different proposed was prepared practically for further investigation and then evaluated for physical and biopharmaceutical properties. The predicted error for observed response of in vitro dissolution studies was found to be -0.57, -1.78 and 0.49% at 2, 12 and 24hr, respectively. Finally, modelling of the in vitro drug release data suggested that, the drug release from the optimized formulation followed Higuchi model and anomalous/non-Fickian type release mechanism.