Ethyl formate - Alternative dispersed solvent useful in preparing PLGA microspheres

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In an effort to substitute methylene chloride with a less toxic solvent, this study was aimed at developing new ethyl formate-based emulsion processes to fabricate poly-D,L-lactide-co-glycolide (PLGA) microspheres. To do so, a polymeric dispersed phase was emulsified in a 1% polyvinyl alcohol aqueous solution at an ethyl formate to aqueous volume ratio of 8:20. Microsphere hardening was then achieved by solvent evaporation and quenching techniques. The average encapsulation efficiency of a model drug progesterone amounted to 95.2 ± 2.7%. When the tendency of ethyl formate and methylene chloride to evaporate to air was compared, the evaporation rate of ethyl formate was 2.1 times faster than that of methylene chloride. The ease with which ethyl formate evaporated to air was beneficial in shortening the microsphere hardening step. For the solvent quenching process, only 80 ml of additional water was required to extract ethyl formate to the aqueous phase, due to its considerable water miscibility. In particular, the timing of ethyl formate quenching affected to a great extent dynamic processes of the breakup of elementary microdroplets into smaller ones. Therefore, variations in quenching time affected microsphere characteristics such as the degree of solvation, size distribution, and tendency to aggregate on drying. The results of this study showed that PLGA microspheres were successfully prepared using the new ethyl formate-based processes. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
StatePublished - 15 Feb 2000


  • Ethyl formate
  • Microencapsulation
  • Microspheres
  • Poly(lactide-co-glycolide)


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