Comparative Bioavailability Study in Dogs of a Self‐Emulsifying Formulation of Progesterone Presented in a Pellet and Liquid form Compared with an Aqueous Suspension of Progesterone

Abstract A pellet formulation of progesterone in a self‐emulsifying system (SES) was prepared by the process of extrusion/spheronization to provide a good in vitro drug release (100% within 30 min, T 50% at 13 min). A three‐way randomized crossover study was performed in six fasted male beagle dogs with these pellets and the same SES liquid formulation, both contained in a hard shell capsule, and an aqueous suspension. The same dose of progesterone (16 mg) in pellets and in the SES liquid formulation resulted in similar AUC, C max and T max values, estimated from progesterone plasma levels by 125 I radioimmunoassay. Although the maximum absorption was slightly retarded (0.5 to 1 h) by SES (pellets and liquid), AUC and C max were approximately seven and nine times greater then those obtained when an aqueous suspension formulation of the same dose of progesterone was administered to the same dogs. These results showed that it was possible to improve the bioavailability of the poorly soluble, poorly permeable progesterone when administered in SES. Moreover, presenting the progesterone in the form of a pellet did not prevent the release of the drug in vivo . These data demonstrate the utility of extrusion/spheronization in delivering a nonaqueous system in a novel solid dosage form. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1495–1502, 2004