Nonhalogenated solvent-based solvent evaporation process useful in preparation of PLGA microspheres

Abstract

The objective of this study was to develop an isopropyl formate-based evaporation process useful in producing poly-D,L-lactide-co-glycolide microspheres. Surprisingly, the evaporating tendency of isopropyl formate was comparable to that of methylene chloride and far better than that of ethyl acetate. After optimization of the isopropyl formate-based process, progesterone was encapsulated into microspheres. Under our conditions, its encapsulation efficiency ranged from 75.1% to 92.6%. Even though all microspheres took spherical geometry, their external and internal morphologies were greatly influenced by progesterone payloads. A GC analysis demonstrated that residual isopropyl formate in various microspheres was 1.8% to 4.0%. Interestingly, progesterone underwent polymorphic transition during the microencapsulation process – the β form was present in microspheres with lower progesterone payloads, whereas the α form predominated over the β one at higher progesterone loads. In terms of human safety and environmental toxicity, isopropyl formate might have an edge over halogenated organic solvents for solvent evaporation.