环孢素A软胶囊囊材的处方优化

Formulation Optimization of Capsule Shells for Cyclosporine A Soft Capsules

以软胶囊内容物中乙醇和1,2-丙二醇含量和环孢素A溶出率为指标,采用正交设计优化软胶囊囊材处方,通过稳定性考察结果优化制备工艺。结果表明,在囊材处方中加入高级多元醇,并在环境相对湿度25%、采用缓慢干燥工艺使胶皮水分在40h内控制在8%,所制备的软胶囊较稳定。与市售环孢素A软胶囊相比,本品内容物中乙醇的迁移量减少,环孢素A的体外溶出行为相似。药动学研究表明,自制软胶囊与市售软胶囊在Beagle犬体内生物等效。

The formulation of capsule shell materials was optimized by orthogonal design with contents of ethanol and 1,2-propanediol and dissolution of cyclosporine A as indexes. The preparation was also optimized according to the results of stability test. The results showed that adding polyols to the capsule shell materials and preparing under relative humidity of 25 % with slow drying speed within 40 h to control the rubber moisture of 8 % could obtain the soft capsules with rather stable properties. Compared with the commercial cyclosporine A soft capsules, the migration amount of ethanol from the content of the prepared soft capsules was decreased while the dissolution behavior of cyclosporine A from the capsules was similar. The results of pharmacokinetics in Beagle dogs showed that these two preparations were bioequivalent.