Formulation Studies and In Vivo Evaluation of a Flurbiprofen-Hydroxypropyl β-Cyclodextrin System

Abstract

The purpose of this study was 1) to investigate in vivo advantages of a flurbiprofen (FPN)-hydroxypropyl β-cyclodextrin (HPβCD) solid dispersion (SD) in rats, 2) to study factors affecting the drug release from SD formulations, and 3) to evaluate the pharmacokinetic profile of the drug when administered as SD, in humans. The solubility of FPN in water and dissolution media was evaluated as a function of HPβCD concentration. The SD was prepared by coevaporation from dilute aqueous NH3 and evaluated in rats. The release of the drug from tablet formulations and capsules of SD was studied in simulated gastric fluid and phosphate buffer, pH 7.2. The bioavailability of drug when administered as SD was evaluated in humans.HPβCD enhanced the solubility of the drug, and SD improved bioavailability and reduced ulcerogenicity of the drug in rats. The type of excipient used affected drug release from tablets. Presence of microcrystalline cellulose, a hydrophilic polymeric excipient, resulted in uptake of water and stabilization of the resulting gels-like structure of HPβCD–containing tablets. This adversely affected drug release. The release from capsules filled with SD was comparable to that obtained from plain SD powder. The drug–HPβCD association constant in water was much lower than the values reported in literature. The bioavailability (which could suffer in case of higher association constant) was enhanced on administration of SD-filled capsules to humans.