Progesterone-loaded microspheres are fabricated by a solvent evaporation process from a poly(D,L-lactide-co-glycolide) (85/15 PLG) and from a-progesterone. Methylene chloride is used as solvent and polyvinyl alcohol and methylcellulose are used as surfactants. The microspheres are characterized by scanning electron microscopy, differential scanning calorimetry, and x-ray powder diagrams. Our study shows that the morphology and the thermal behavior of PLG microspheres can vary significantly with progesterone loading and sample thermal history. Below and at 16.5% loading the microspheres exhibit a smooth outer surface.
Above 23% loading, the surface becomes rough, embedded by copolymer particles or well-defined crystals. Pores and cracks can also be observed. Below 35% the progesterone is molecularly dispersed. At 35% and above crystal domains of the steroid appear and two crystalline forms are found: a-and p-progesterone. The physical state of progesterone and the nature of its crystal domains dispersed in the PLG matrix can change during storage. Also a progressive development of an endothermic peak at the T , event of the copolymer is observed during storage. No well defined relationship of peak size to progesterone loading can be shown.
IN T RODUC T ION
Many new drug delivery systems are formed by intimately mixing a polymer carrier and drug.'-4 A variety of physico-chemical interactions between the carrier and drug can occur. These interactions influence the therapeutic performance and stability of the final device. Accordingly, an effort is being made to characterize the morphology of drug delivery devices, especially microspheres fabricated from polymers by a solvent casting process. Previous studies utilized poly(D,L-lactide) microspheres loaded with progesterone5 or hydrocortisone.6 This article summarizes results of a morphology study of progesterone-loaded microspheres fabricated from a poly(D,L-lactide-co-$To whom correspondence should be addressed.