Response surface design: optimization of a sustained release formulation of ketorolac tromethamine

Abstract

The main objective of this present study is to formulate sustained release tablets of Ketorolac Tromethamine using a 32 full factorial design and to systemically optimize the drug release profile using a design expert software. Ketorolac Tromethamine is a potent NSAID drug that is used to treat moderate to severe pain, including pain after any surgery, acute musculoskeletal pain as well as pain associated with post uterine cramping. Ketorolac Tromethamine has a short biological half-life of 4-6 hours and frequent administration of the drug can cause GI problems. It is thus considered a suitable drug for doing formulation development to reduce the frequent administration of drug and also to reduce adverse effects of GI, thus making it more patient compliant and giving a constant therapeutic effect. In total, nine formulations of sustained release Ketorolac Tromethamine were prepared using different concentrations of the rate retarding polymer - Methocel K100M CR and Methocel K4M CR by direct compression. Each of the excipients were selected by performing compatibility study using Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC). In vitro dissolution study was performed for all the formulations to obtain the drug release profile of sustained release tablets of Ketorolac Tromethamine and the dissolution profile were fitted into the different kinetic models for analysis. Among all the kinetic models, most of the formulated matrix tablets followed first order drug release kinetics which indicated that the drug release follows anomalous (non-Fickian) mechanism. It was found, from the responses produced by the software, that the polymer combination used in the formulation of sustained release matrix tables at different ratios has control on the drug release. From the nine (F1-F9) formulations, F5 was finally selected as optimum formulation.