Risk based approach for design and optimization of site specific delivery of isoniazid

Abstract

The research envisaged focuses on risk management approach for development and optimization of enteric coated tablet of isoniazid giving extended release in pH 6.8 phosphate buffer. Risk assessment using failure mode and effects analysis was done to depict the effects of unambiguous failure modes related to particular formulation/process variable. A 23 full factorial design was employed for optimization of core tablet to investigate effect of amount of Polyox WSR 303 (A), hardness (B) and amount of ethyl cellulose (C) on percent drug release in pH 6.8 phosphate buffer. Main effects and interaction plots were generated to study effects of variables. The selection of optimized formulation was done on overlay contour plots and desirability function. The optimized formulation exhibited percent drug release at first hour of 26.97 %, second hour of 44.20 %, fourth hour of 66.15 % and eighth hour of 97.9 % in phosphate buffer pH 6.8. Akaike information criteria and Model selection criteria revealed that the model was best described by Korsmeyer–Peppas power law. The Kopcha and Peppas–Sahlin model revealed diffusion as predominant mechanism of release which may be due to high solubility of drug and drug loading. Enteric coating optimization revealed weight gain of 10 % w/w as optimum; giving nil release of isoniazid in 0.1 N hydrochloric acid. The composite desirability for optimized formulation computed using equations and software were 0.91 and 0.90 respectively. Capability analysis on reproducibility batches revealed all indices above 1.33 signifying process was within control of producing batches as per desired specifications.