PREFORMULATION STUDY OF PROGESTERONE FROM DOSAGE FORM DESIGN - RELEASE CHARACTERISTICS AND BIOAVAILABILITY OF PROGESTERONE SUPPOSITORIES

Progesteron was preformulated as coprecipitate with polyvinyl-pyrrolidone (PVP) 40.000 and 44.000 at different ratios. Progesterone dissoluted faster from coprecipitate with PVP 40.000 than from that with PVP 44.000. As the amount of PVP 40.000 increased in the coprecipitate the dissolution rate of the drug was increased up to 1 : 8; drug : PVP ratio. The solubility profile of the drug in presence of PVP 40.000 and differential UV spectra of the drug in presence of this polymer indicates that a sort of molecular interactions may occur between the drug and PVP 40.000-X-Ray diffraction patterns revealed that the drug was changed to amorphous state on its coprecipitation with PVP 40.000 at 1 : 8 ratio. The melting range of progesterone was slightly decreased at this ratio. The data of dissolution patterns and the dialytic rate constants were included. Progesterone-PVP coprecipitate exhibited extremely fast release for the drug when included in cocoa butter, witepsol(R) H15 and polyethylene glycol suppositories. The latter base was most efficient than the other bases because of the solubilizing effect of polyethylene glycol (PEGs) on the drug. Studies were conducted to examine the absorption of progesterone in rabbits following rectal administration of the two formulations containing progesterone alone and progesterone-PVP 40.000 (1 : 8) coprecipitate in PEG suppositories. The serum progesterone concentration was determined by using direct radio immunoassay technique using [I-125]-labeled progesterone after a single dose of 5 mg/kg progesterone in an PEG suppositories. The maximum serum concentration (C(max)) after progesterone only was 3.841 l mu-g/ml and lower than the coprecipitate, which was 4.229-mu-g/ml. The histological examination of the mammary glands of the treated rabbits stained with haematoxylin and eosin for general histology indicates that progesterone-PVP coprecipitate increased the number of alveoli and the proliferation of the mammary lobules than the hormone alone.