Influence of physicochemical interactions on the properties of suppositories V. The in vitro release of ketoprofen and metronidazole from various fatty suppository bases and correlations with in vivo plasma levels

Abstract Various membrane and non-membrane methods of in vitro measurement of drug release from suppositories were examined from a literature survey and using 200 mg fatty suppository formulations containing 7.4 mg of ketoprofen or 46 mg of metronidazole. The fatty suppository formulations differed in the bases, which were either commercial bases or binary mixtures of pure triglycerides. Rotation about various axes of a cylindrical cell fitted with a membrane at each end gave essentially the same in vitro release profile provided that the molten base did not coat the membrane surface. Linear correlations between the drug concentration released in vitro and the in vivo levels in plasma at given time intervals after administration of various suppository formulations to rats were generally not statistically significant. On the other hand, comparison of these in vivo data with the non-membrane in vitro results using rank order correlation methods on paired data at each time interval for a number of suppository formulations showed statistically significant correlations. Although plastic viscosities did not correlate with in vitro release, the base with the lowest viscosity always gave the fastest release of either drug. On balance, non-membrane methods of measuring in vitro drug release are generally favoured.