This study investigated the dynamic effect of the emulsification process on emulsion droplet size in manufacturing microspheres using ethyl acetate as an organic solvent. A dispersed phase consisting of poly(lactide-co-glycolide) and ethyl acetate was emulsified in a poly(vinyl alcohol) aqueous solution for a predetermined time ranging from 2 to 9, 16, 23, 30, 40, 50, or 60 minutes. Ethyl acetate was then quickly extracted to transform emulsion droplets into solidified microspheres, and their size distribution was determined. This experimental design allowed quantification of the size distribution of emulsion droplets over the course of emulsification. When emulsification time was extended from 2 to 60 minutes, the emulsion droplets decreased in size from 98.1 to 50.3 μm and their surface area increased from 0.07 to 0.29 m2/g. Overall, prolonging emulsification time up to 60 minutes resulted in the progressive evolution of smaller emulsion droplets (1-60 μ m) and the simultaneous disappearance of larger ones (>81 μ m). Increases in the total number of microspheres and their surface area were caused mainly by continuous fragmentation of emulsion droplets before ethyl acetate extraction. The increase in the smaller microsphere population might also be due in part to shrinkage of microspheres. These results show that the onset of ethyl acetate extraction influenced the kinetics of the breakup and formation of emulsion droplets, thereby affecting to a great extent the size distribution of microspheres.
- Ethyl acetate