Microparticle preparation by a propylene carbonate emulsification-extraction method

The use of various harmful organic solvents for microparticle formulations is still widespread. Here, an alternative low toxicity solvent (propylene carbonate; PC) is proposed for the preparation of poly(lactic-co-glycolic-acid) (PLGA) microparticles. Based on the classical emulsification-solvent extraction methodology, the use of PC offers the unique advantage of an additional solvent extraction step using hydrolytic solvent cleavage during microparticle preparation. Spherical, rough-surfaced microparticles were obtained with a volume median diameter range from 20 to 60 µm. The residual PC content has been identified to be the major factor for the solidification hindrance, leading to polymeric Tg shifting due to a plasticizing effect. When applying the enhanced PC extraction step, the residual PC content was lowered from 8.8% to 2.7% and subsequently Tg values shifted from 8.2 to 37.7°C. Additionally, the hydrolytic solvent cleavage confirmed to have no impact on the PLGA stability. This method presents a significant advancement towards replacing of conventional solvents in the microparticle preparation due to more efficient solvent extraction.



PC revealed excellent properties as a low toxic organic solvent for polyester microparticle

preparation. Especially, the unique technical option of an enhanced PC extraction step enabled a

viable preparation method and solved the problems caused by high viscosity and residual solvent

content encountered with other non-toxic solvents. Accordingly, the enhanced PC extraction step

can be considered as a major advancement for the techniques employing low toxic cyclic esterbased

solvents. The fact that no degradation issues were identified when other ester-based

excipients were used underlines the robustness of the method and suggests numerous

pharmaceutical applications.


Microparticle preparation by a propylene carbonate emulsification-extraction method