Medicament Release from Suppository Bases I: Physicochemical Characteristics and Bioavailability of Indomethacin in Rabbits

Abstract

This investigation was designed to determine the in vitro release of indomethacin from suppository bases and the in vivo bioavailability in rabbits. Suppositories containing 25 mg of indomethacin were made by the fusion method with theobroma oil, esterified fatty acids (C10-C18), and polyethylene glycol 1000. To produce an exact dosage form, a formula for the determination of the displacement value was derived, and it was found that theobroma oil > esterified fatty acids (C10-C18) > polyethylene glycol 1000. The suppository hardness was determined by using appropriate apparatus and it was found that the esterified fatty acids (C10-C18) allowed the formation of more brittle suppositories. The release rates were determined with the USP dissolution apparatus, with or without cellophane membrane, and it was found that polyethylene glycol 1000 > esterified fatty acids (C10-C18) > theobroma oil. The bioavailability of indomethacin after rectal administration was greater with polyethylene glycol base. Significant correlation was obtained during the first 45 min between the in vitro release (dialyzing tubing) and the in vivo bioavailability.