Toward Understanding the Effect of Solvent Evaporation on the Morphology of PLGA Microspheres by Double Emulsion Method

During the fabrication of poly(lactide-co-glycolic acid) (PLGA) microspheres by the water/oil/water (W1/O/W2) emulsion solvent evaporation method, water permeation coupled with dichloromethane (DCM) volatilization represents a critical process affecting the microsphere morphology. In this work, the mechanism of pore formation in PLGA through water permeation has been verified. By molecular simulations, the diffusion coefficients of water with different DCM contents were determined. The results showed that the diffusion coefficient decreased rapidly from 53.33 × 10–6 to 6.73 × 10–6 cm2/s after decreasing the DCM mass fraction from 94 to 63%. Furthermore, the higher stirring speed and lower volume of the external aqueous phase promoted the DCM volatilization. Two different mass transfer stages were identified for water permeation, and the first stage could be considered the main mass transfer window because of its high diffusion coefficient. The morphology of PLGA microspheres confirmed the existence of a relationship between water permeation and DCM volatilization.