THE MORPHOLOGY OF PROGESTERONE-LOADED POLYSTYRENE MICROSPHERES

An in-liquid drying process has been used to form progesterone-loaded microspheres from polystyrene. Methylene chloride was the casting solvent. The microspheres evaluated had initial progesterone payloads of 0-60 wt.%. Scanning electron microscopy shows that microspheres loaded with 0-50 wt.% drug have a smooth surface and a spherical geometry. When the progesterone loading is raised to 60 wt.%, irregularly shaped microspheres are isolated. Differential thermal analyses (DTA) establish that the polystyrene T(g) values decrease as progesterone loading increases from 0 to 50 wt.%. This is evidence that progesterone has finite solubility in the polystyrene matrix. DTA analysis of heat-treated microspheres and X-ray analysis confirm this finding and show that microspheres with a progesterone content of 28.6-60 wt.% contain crystalline drug domains dispersed in the polystyrene matrix. At 28.6-37.5% progesterone loadings, the crystalline progesterone exists as a mixture of the alpha- and beta-polymorphs. At 50 and 60% loading, only the alpha-polymorph forms appear. The aging of the polystyrene T(g) event on storage was shown. Freshly made microspheres or microspheres heat treated above T(g) and immediately quench-cooled, have a diffuse T(g). Upon storage, this event develops an endothermic peak.