Physical and chemical stability of miconazole liposomes prepared by supercritical aerosol solvent extraction system (ASES) process.

摘要

The aerosol solvent extraction system (ASES) process was applied to prepare miconazole (MCZ) liposomes in a dry and reconstitutable form, the optimized temperature and pressure of which were 35 degrees C and 8.0 MPa, respectively. The influence of compositions of phosphatidylcholine (PC), cholesterol (CHOL), and poloxamer 407 (POLOX) as well as the pH of hydration medium on physical and chemical stability of both dry microparticles and liposomes hydrated from them were examined following storage at 4 degrees C and 25 degrees C for 3 months. MCZ microparticles in dry powder were stable on storage at 4 degrees C but degraded considerably after storage at 25 degrees C. MCZ liposomes hydrated from dry ASES-prepared microparticles at pH 4.0 tended to aggregate, whereas those hydrated at pH 7.2 tended to reduce in size on storage, especially with the addition of CHOL. Liposomes with high MCZ content stored at 4 degrees C degraded faster than when stored at 25 degrees C. Addition of POLOX tended to retard thedegradation of MCZ liposomes, whereas CHOL appeared to enhance the degradation on storage under both conditions. The chemical degradation of MCZ liposomes appeared to follow the acid-catalyzed hydrolysis. The MCZ liposomes prepared by the ASES process in this study were substantially internalized after being incubated with human lymphocytes.