DoE based formulation and optimization of sustained release tablet dosage form of diacerein

Abstract

Osteoarthritis is a type of arthritis that occurs mainly in elderly people and is characterized by pain in joints, stiffness, etc. which may lead to disability. Diacerein is a new anti-inflammatory drug which is more profoundly said to be an anti-arthritic agent since pharmacological studies found it to be effective in all kinds of arthritis as analgesic and anti-inflammatory. Moreover, it is also as agent that brings about structural change unlike normal NSAIDs. The aim of the study was to develop a sustained release tablet dosage form of diacerein that will be an optimized formulation and highly patient compliant. The method involves designing the formulation and controlling release by using blends of two HPMC based release retardants. Drug-excipient compatibility tests were carried out using DSC and FTIR spectroscopy. Based on the fact that no incompatibility was present, step was taken to prepare trial batches of tablets of nine different formulations. The physical evaluation of both the drug-excipient powder mixtures and tablets of the nine formulations were performed and results were found to be within acceptable ranges for all tests. Dissolution profile of tablets were done and the release data was then put into zero order, first order, Higuchi, Korsmeyer-Peppas and Hixon-Crowell kinetic models. The release data was simulated in Design Expert Software to carry out statistical analysis and the effect of both polymers on release patterns were observed after 1,4 and 8 hours in terms of contour plots and 3D surface plots, which were all significant (p<0.05) . Finally, the optimization overlay plot was obtained from which the optimized formulation was determined.