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

The characteristics of suspension-type matrices for the controlled release of hydrophobic drugs, based on crosslinked polyethylene oxides) (cr-PEO) have been investigated using progesterone (PGT) as a model drug. The drug amounts that can be reproducibly loaded in polymer by an impregnation technique are limited by crystalline drug expulsion from the matrix during solvent evaporation, depending on the degree of crosslinking of the polymer. cr-PEO of crosslinking degrees adequate to confer the required mechanical stability on the swollen matrix can be loaded with no more than 8-10% drug. A polymer with low crosslinking degree was loaded with up to 39% drug, but showed poor mechanical properties in its fully swollen state. The thermal behavior of the PGT-cr-PEO systems, as assessed by DSC, indicates drug-polymer interactions typical of monotectic dispersions. PGT release from cylindrical cr-PEO matrices is not influenced by the matrix swelling kinetics and is consistent with a model assuming that drug diffusion in the polymer phase of the fully swollen hydrogel is the rate-controlling factor. A cr-PEO of comparatively low degree of crosslinking was shown to match uncrosslinked polyethylene glycols with respect to the ability to enhance the dissolution rate of high PGT loads.