卡马西平微胶囊的超临界制备及溶出性能研究

Supercritical preparation and dissolution property of carbamazepine microcapsule

为提高卡马西平药物的溶出性能,基于超临界流体注入(SFI)技术,先后开展了聚乳酸-羟基乙酸(PLGA)、聚乙二醇单甲醚-聚乳酸-羟基乙酸(MPEG-PLGA)聚合物包裹卡马西平的微胶囊制备实验。结合差示扫描量热法和红外光谱分析,探讨了卡马西平在微胶囊中的形态及其与聚合物分子间的作用,同时实测了相应的药物体外溶出性能。结果表明:该文所制PLGA及MPEG-PLGA载药微胶囊中,卡马西平药物分子均呈无定形状态,均匀分散于包裹剂中;MPEG-PLGA载药微胶囊内药物与聚合物分子间有较强的相互作用,其塑性优于PLGA载药微胶囊;以MPEG-PLGA为聚合物基体的微胶囊的药物溶出速率明显高于单纯以PLGA为基体的微胶囊,且外加的MPEG分子量越小、相应PLGA中n(LA):n(GA)越低越利于药物溶出速率的提高;为提高药物溶出速率,进行SFI时也可适当增加微胶囊的载药量,但不宜过高,当载药量从9.8%、28.3%升至35.8%时,卡马西平药物的溶出速率依次增大,但当载药量达45.2%时,对应微胶囊的溶出速率不升反降。

In order to improve the dissolution property of carbamazepine,corresponding experiments on producing microcapsule of carbamazepine wrapped by poly lactic-co-glycolic acid （ PLGA ） or methoxy polyethylene glycol-poly lactic-co-glycolic acid （ MPEG-PLGA ） are carried out using supercritical fluid impregnation （ SFI ） . The forms of carbamazepine in the polymer matrices and molecular interactions between carbamazepine and the polymers are characterized by differential scanning calorimetry and infrared spectroscopy. The dissolution of carbamazepine in vitro is determined. The results show that：for the microcapsule using PLGA or MPEG-PLGA to carry drug, the carbamazepine molecules present amorphous state and disperse evenly in the matrices;the molecular interaction between carbamazepine and MPEG-PLGA is strong, and the plasticity of MPEG-PLGA microcapsule is better than that of PLGA microcapsule;the drug dissolution rate of the MPEG-PLGA matrix is obviously higher than that of the PLGA matrix,and the drug dissolution rate increases with the decrease of molecular weight of the adscititious MPEG and n（ LA）：n（ GA）;the drug dissolution rate can be appropriately enhanced when the drug loading rises from 9 . 8%,28 . 3%to 35. 8%,when the drug loading reaches about 45. 2%,the drug dissolution rate begins to descend.