The rapid expansion from a supercritical solution with a nonsolvent (RESS-N) was applied to the formation of polymeric microcapsules containing medicines such as p-acetamidophenol, acetylsalicylic acid, 1,3-dimethylxanthine, flavone, and 3-hydroxyflavone. A suspension of medicine in carbon dioxide (CO2) containing a cosolvent and dissolved polymer was sprayed through a nozzle to atmospheric pressure. The pre-expansion pressure was 10-25 MPa, and the temperature was 308-333 K. The polymers were poly(L-lactic acid) (molecular weight = 5000), polyethylene glycol) (PEG; PEG4000, molecular weight = 3000; PEG6000, molecular weight = 7500; and PEG20000, molecular weight = 20,000), poly(methyl methacrylate) (molecular weight = 15,000), ethyl cellulose (molecular weight = 5000), and PEG-poly(propylene glycol)-PEG triblock copolymer (molecular weight = 13,000). The solubilities of the polymers as coating materials and these medicines as core substance were very low in CO2. However, the solubilities of these polymers in CO2 significantly increased with the addition of low molecular weight alcohols as cosolvents. After RESS-N, polymeric microcapsules were formed according to the precipitation of the polymer caused by a decrease in the solvent power of CO2. This method offered three advantages: (1) enough of the coating polymers, which were insoluble in pure CO2 dissolved; (2) the microparticles of the medicine were encapsulated without adhesion between the particles because a nonsolvent was used as a cosolvent and the cosolvent remaining in the mixture was removed by the gasification of CO2; and (3) the polymer-coating thickness was controlled with changes in the feed composition of the polymer for drug delivery. © 2003 Wiley Periodicals, Inc.
CITATION STYLE
Matsuyama, K., Mishima, K., Hayashi, K. I., Ishikawa, H., Matsuyama, H., & Harada, T. (2003). Formation of microcapsules of medicines by the rapid expansion of a supercritical solution with a nonsolvent. Journal of Applied Polymer Science, 89(3), 742–752. https://doi.org/10.1002/app.12201
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