Abstract

FORMULATION AND EVALUATION OF PULSATILE DRUG DELIVERY CAPSULE OF KETOROLAC TROMETAMOL

Chauhan Amitsingh* and Dr. L. D. Patel

Abstract

A time and pH dependent pulsatile drug delivery system of ketorolac trometamol (KT) was proposed for the chronotherapeutic treatment of rheumatoid arthritis. It was fabricated in three steps. First, KT was entrapped with cellulose acetate. Second, these core microspheres were coated with eudragit L-100 and S-100. Finally, the coated microspheres were filled in capsule with a soluble cap, sealed with hydrogel-plug (HPMC K100M/guar gum/xanthan gum) and entire capsule was enteric coated with Hydroxypropyl methylcellulose Phthalate (HPMC Phthalate). SEM revealed that the microspheres were discrete and uniform. The size distribution of the microspheres was narrow with an arithmetic mean size of 368.81μm. During dissolution, pulsatile capsules remained intact in pH 1.2 for 2 hours indicating the enteric coating efficiency of HPMC Phthalate. The enteric coat dissolved when pH was changed to 7.4, leaving the soluble cap apart. Then, the exposed polymeric plug absorbed the surrounding fluid, swelled and released the drug through solvent matrix. When polymeric plug was completely wetted by dissolution fluid, it was easily ejected out of the capsule and liberated the microspheres in to the simulated colonic fluid (pH 6.8 phosphate buffer). No drug release was observed in first three hours from all pulsatile capsules which was required for chronotherapeutic delivery of KT. The rank order of polymer plug for sustaining drug release was HPMC K100M>guar gum>xanthan gum. The designed pulsatile delivery systems exhibited first order diffusion controlled drug release. The study conclusively proved that the designed pulsatile capsule is a promising chronotherapeutic delivery system for rheumatoid arthritis.

Keywords: Ketorolac trometamol; rheumatoid arthritis; enteric coating; polymeric plug; chronotherapeutic delivery.