Abstract

FORMULATION AND EVALUATION OF CONTROLLED ONSET EXTENDED RELEASE MICROSPHERES OF KETOROLAC TROMETAMOL USING FACTORIAL DESIGN.

Chauhan Amit Singh* and Dr. L. D. Patel

ABSTRACT

A controlled onset extended release dosage form of ketorolac trometamol (KT) is proposed for the treatment of rheumatoid arthritis. KT loaded cellulose acetate microspheres were prepared by emulsion solvent evaporation technique. On the basis of trial batches, Span 80 as a surfactant and light liquid paraffin as dispersion medium were fixed as preliminary parameters for preparation of KT loaded cellulose acetate microspheres. Amount of cellulose acetate and Span 80 played important role in stable formulation; hence selected as independent variables in 32 factorial design. The % practical yield and % encapsulation efficiency were selected as dependent variables. Multiple regression analysis and response surface plots were used to study the main, quadratic and interaction effects of the variables on the responses. The responses were measured and further model was fitted by carrying out multiple regression analysis and F-statistic to identify statistically significant term. Based on the results, batch F6 was selected as optimized formulation. The size distribution of the microspheres was found to be narrow with arithmetic mean size of 354.56μm and average size was in the range of 327.5μm to 390μm. In SEM photographs, the microspheres found to be porous and remained intact after release study. 26.93% drug release was obtained in first 2 hours, 75.01% in 8 hours and 98.89% in 12 hours. The mechanism of drug release from the prepared microspheres followed non-fickian diffusion controlled release kinetics. The study conclusively proved that a multiparticulate system having controlled-release property is promising for the treatment of rheumatoid arthritis.

Keywords: Ketorolac trometamol; rheumatoid arthritis; emulsion solvent evaporation; factorial design; controlled-release.