鸦胆子油结肠定位硬胶囊制备工艺和质量标准

Preparation Technology and Quality Standard of Bruceae Fructus Seed Oil Colon-specific Hard Capsules

目的:制备p H依赖型的口服结肠定位给药的鸦胆子油硬胶囊。方法:通过薄膜包衣法制备结肠定位硬胶囊,以崩解时限为指标,在单因素试验基础上,通过正交设计优选包衣处方,考察不同包衣处方硬胶囊在不同p H条件下的崩解情况。建立鸦胆子油硬胶囊中油酸和亚油酸的HPLC含量测定方法,流动相甲醇-水(83∶17),流速1.0 m L·min-1,检测波长242 nm。结果:制备的结肠靶向给药鸦胆子油硬胶囊在p H 6.8以下时均不崩解,只有在p H 7.8下才迅速崩解,使药物达到结肠定位释药的目的;最佳包衣处方为丙烯酸树脂Ⅲ号1.6 g,eudragit RL100和eudragit RS100各0.2 g,邻苯二甲酸二乙酯1.5 m L,蓖麻油1 m L,无水乙醇、丙酮各47.5 m L,包衣增重3.8%。HPLC测定鸦胆子油提取物中各种脂肪酸的分离度均符合要求,亚油酸、油酸质量浓度分别为116.37,288.26 mg·L-1,相对质量分数依次为2.91%,7.21%。结论:优化的处方能达到结肠定位的要求。建立的含量测定方法准确可靠、灵敏度高、重复性好,可用于鸦胆子油控释胶囊的质量控制。

Objective： To prepare pH sensitive oral colon-specific drug delivery for Bruceae Fructus seed oil hard capsules. Method： Colon-specific drug delivery of Bruceae Fructus seed oil hard capsules were prepared by thin film coating method, with disintegration time as index, based on single factor tests, orthogonal design was adopted to optimize coating prescription, disintegration of hard capsules with different coating prescriptions under different pH conditions were investigated. HPLC was performed on determination of linoleic acid and oleic acid in Bruceae Fructus seed oil hard capsules with mobile phase of methanol-water （83： 17）, flow rate of 1.0 mL ·min^-1 and detection wavelength at 242 nm. Result： These prepared colon-specific drug delivery of Bruceae Fructus seed oil hard capsules below pH 6.8 were not collapse and only under pH 7.8 rapidly disintegrate, make this drug to achieve purpose of colon specific delivery; optimum coating formulations was as follows： acrylic resin Ⅲ 1.6 g, eudragit RL100 of 0.2 g, eudragit RS100 of 0.2 g, diethyl phthalate 1.5 mL, castor oil 1 mL, absolute ethyl alcohol 47.5 mL, acetone 47.5 mL, coating weight 3.8%. HPLC determination of separation degree of all kinds of fatty acids in Bruceae Fructus seed oil extract conformed to requirements, concentrations of linoleic acid and oleic acid were 116.3 Conclusion ： This opti method is reproducible 7, 288.26 mg · L^-1 , relative mass fractions were 2.91% and 7.21% , respectively. mized prescription can achieve positioning requirement of colon specific. This assaying and accurate with high sensitivity, which can be used for quality control of Bruceae Fructus seed oil controlled release capsules.