DESIGN AND OPTIMIZATION OF IMMEDIATE RELEASE TABLETS OF HYDROCHLOROTHIAZIDE USING THE DESIGN OF EXPERIMENTS APPROACH

The aim of the present study was to develop and optimize immediate release tablets using hydrochlorothiazide (HCTZ) as a model drug candidate applying Design of Experiments (DoE) approach. Immediate release tablets were prepared using corn starch as a disintegrant and Polysorbate 80 as a solubilizer. Risk assessment was carried out with subsequent application of 22 factorial design in duplicate for evaluating the interactions and effects of the design factors on critical quality attributes. The design space was obtained by applying DOE and multivariate analysis, so as to ensure desired disintegration time (DT) and in vitro drug dissolution. Immediate release tablets were evaluated for hardness, thickness, friability and in vitro drug dissolution. Optimized formulation obtained from the design space exhibits DT of around 38s, while dissolution time, T96% (time required to release 96% of the drug) was about 45 min. The independent variables have a significant effect over the dependent responses, which can be deduced from Contour plots and surface response graphs. The predicted values matched well with the experimental values and the result demonstrated the feasibility of the design model in the development and optimization of HCTZ immediate release tablets.