胆酸钠/磷脂混合胶团对环孢素A的增溶作用研究

Study on solubilization of CyA by using sodium cholate/lecithin mixed micelles

目的 研究胆酸钠 /磷脂混合胶团对难溶性多肽环孢素A(CyA)的增溶作用。方法 采用共沉淀法制备胆酸钠 /磷脂混合胶团 ,并对影响增溶作用的处方及工艺进行考查。结果 相同胆酸钠浓度条件下 ,混合胶团对CyA的增溶能力远大于胆酸钠胶团 ,增大混合胶团中的磷脂用量或者降低胆酸钠 /磷脂 (摩尔比 )均有利于提高混合胶团对药物的增溶能力。升高水合温度 ,增加水合介质的离子强度 ,加入抗氧化剂维生素E(VE)及胆固醇 ,均不同程度的降低了混合胶团的增溶能力。通过优化各个影响因素可获得最大的增溶量 (>5mg/mL) ,增加CyA溶解度 10 0倍以上。结论 胆酸钠 /磷脂混合胶团可以成为CyA等难溶性多肽药物的一种新型增溶载体。

OBJECTIVE To investigate the effect of solubilization by using sodium cholate/lecithin mixed micelles on poorly soluble drug, CyA. METHOD The mixed micelles was prepared by coprecipitation. The formulation components and preparation procedures which may affect the solubility were studied.RESULTS The molar ratio of sodium cholate to lecithin, and their concentration affected the solubility of CyA in the micelles. Ionic strength of the dispersion medium, temperature, and the additives such as VE and cholesterol also altered the solubilization capacity of the micelles. The largest solubility(>5mg/mL) of CyA in the micelles solution can be achieved by optimizing the studied factors. There is a more than 100 fold and 12 fold increase to the solubility of CyA in water and in cholatemicellar solution, respectively.CONCLUSION It is desirable that mixed micelles can be a new drug carrier system for some poorly soluble drugs.