Prediction of Process Variables in Indomethacin Ternary System Using Experimental Design Solid State Characterization and In-vivo Studies

Palanisamy Mohanraj*, Khanam Jasmina, Balasubramaniam Deepak, A Bharathi, C Siva

Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

ABSTRACT

The aim of the present investigation is (i) to apply and analyze response surface methodology to optimize the preparation method of indomethacin solid dispersion which involves three significant independent variables: amounts of each carrier β-Cyclodextrin (βCD), Polyvinyl pyrrolidone (PVP K30), and solvent mixture (ethanol-water), (ii) to characterize by solid state analysis, and evaluate by in vivo study. A 3-factor, 3-level ‘Central Composite Face Centered design’ was used to explore the quadratic and linear response surfaces and to construct a second order polynomial models which can predict responses ‘aqueous solubility’, and ‘% release’ with minimum % error. In addition, the desirability function approach was applied to obtain the best compromise among the multiple responses. It was found that both the independent variables played a significant role on the solubility and percentage drug release. The solid state studies enable the phase (crystalline) transform of drug which influences its solubility and drug release. The enhancement of Cmax and AUC0-24 of indomethacin (in solid dispersion) with that of pure drug imply the increase in bioavailability of drug.

Keywords:

Solubility, Dissolution rate, Response surface methodology, Desirability function