The biodegradable polyesters, poly(hydroxybutyrate) (PHB) and poly(hydroxybutyrate-hydroxyvalerate) (PHBV) were investigated for use as sustained delivery carriers of a model drug, progesterone. Spherical microspheres containing the drug were prepared by an emulsion solvent-evaporation method with gelatin as an emulsifier. Methylene chloride as the polymer solvent yielded smoother microspheres than chloroform. The surface texture was also dependent upon the temperature of the preparation and polymer used. Surface crystals were observed when the drug loading was increased beyond 5 per cent w/w. Thermograms of the microspheres did not show an endotherm corresponding to the melting of the drug because the drug dissolved in the melted polymer while heating. The amount of residual solvent in the microspheres (gas chromatographic assay) ranged from 3.4 to 58.4 ppm and was dependent on the processing temperature, concentration of the polymer in the solvent and the polymer composition. In vitro release of the drug was slowest from microspheres made from copolymer containing 9 per cent hydroxyvalerate. A less porous microsphere matrix was formed by this copolymer.

The pharmacokinetics of progesterone were characterized in ovariectomized female rats. Progesterone was administered intravenously at a dose of 500 micrograms kg-1. Serum progesterone concentrations were determined by radioimmunoassay. Serum concentrations of progesterone were best described by a two-compartment model with elimination from the central compartment. The distribution and elimination phase half-lives were 0.13 +/- 0.024 (mean +/- SD) and 1.21 +/- 0.21 h, respectively. Elimination of the steroid was rapid with a total clearance of 2.75 +/- 0.42 l h-1 kg-1. Progesterone was widely distributed in the rat with a steady state volume of distribution of 2.36 +/- 0.23 l kg-1, a volume of the central compartment of 0.86 +/- 0.24 l kg-1 and a volume of the peripheral compartment of 1.50 +/- 0.19 l kg-1. The results of this study suggest that the ovariectomized female rat is a suitable animal model for examining the pharmacokinetics of progesterone.

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