A novel method of preparing PLGA microcapsules utilizing methylethyl ketone

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.