A STUDY OF CONTROLLED-RELEASE SYSTEMS FOR PROGESTERONE BASED ON CROSS-LINKED POLY(ETHYLENE OXIDES)

The characteristics of suspension-type matrices for the controlled rel ease of hydrophobic drugs, based on crosslinked polyethylene oxides) ( cr-PEO) have been investigated using progesterone (PGT) as a model dru g. The drug amounts that can be reproducibly loaded in polymer by an i mpregnation technique are limited by crystalline drug expulsion from t he matrix during solvent evaporation, depending on the degree of cross linking of the polymer. cr-PEO of crosslinking degrees adequate to con fer the required mechanical stability on the swollen matrix can be loa ded with no more than 8-10% drug. A polymer with low crosslinking degr ee was loaded with up to 39% drug, but showed poor mechanical properti es in its fully swollen state. The thermal behavior of the PGT-cr-PEO systems, as assessed by DSC, indicates drug-polymer interactions typic al of monotectic dispersions. PGT release from cylindrical cr-PEO matr ices is not influenced by the matrix swelling kinetics and is consiste nt with a model assuming that drug diffusion in the polymer phase of t he fully swollen hydrogel is the rate-controlling factor. A cr-PEO of comparatively low degree of crosslinking was shown to match uncrosslin ked polyethylene glycols with respect to the ability to enhance the di ssolution rate of high PGT loads.