A novel method of preparing PLGA microcapsules utilizing methylethyl ketone

Hongkee Sah, Melissa S. Smith, Rey T. Chern

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Purpose. To substitute dichloromethane with a safer solvent, a solvent extraction process using methylethyl ketone (MEK) was developed to prepare poly(d,l-lactide-co-glycolide) microcapsules. Methods. The MEK dispersed phase containing PLGA and progesterone was emulsified in the MEK-saturated aqueous phase (W1) to make a transient oil-in-water (O/W1) emulsion. It was then transferred to a sufficient amount of water (W2) so that MEK residing in polymeric droplets could be extracted effectively into the continuous phase. Results. This solvent extraction process provided the encapsulation efficiency for progesterone ranging from 77 to 60%. The amount of MEK predissolved in W1, as well as the degree of progesterone payload, influenced the encapsulation efficiency. The leaching profile of MEK analyzed by GC substantiated that, upon dispersion of O/W1 to W2, MEK quickly diffused into the continuous phase. Such a rapid diffusion of MEK from and the ingression of water into polymeric droplets produced hollow microcapsules, as evidenced by their SEM micrographs. Conclusions. When solvent extraction/evaporation techniques are employed for preparing PLGA microcapsules, water-immiscibility of a dispersed phase is not an absolute prerequisite to the successful microencapsulation. Adjustment of an initial extraction rate of MEK and formation of a primary transient O/W1 emulsion are found to be very crucial not only for the success of microencapsulation but also for the determination of microcapsule morphology.

Original languageEnglish
Pages (from-to)360-367
Number of pages8
JournalPharmaceutical Research
Issue number3
StatePublished - 1996


  • Methylethyl ketone
  • Microcapsules
  • Morphology
  • poly(d,l-lactide-co-glycolide)
  • Solvent extraction/evaporation


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