盐酸雷洛昔芬自微乳化给药系统处方的初步研究

摘要

目的：研究盐酸雷洛昔芬（ Raloxifene hydrochloride）自微乳制剂的处方。方法通过考察盐酸雷洛昔芬在各种辅料中的溶解度，对各种辅料的自乳化性能进行筛选；采用正交设计试验优化处方，分别以透光率、乳化速度、有无油层、药物溶解难易程度及三相混合是否分层为评价指标，确定最佳的油相，乳化剂，助乳化剂组合。结果盐酸雷洛昔芬在乙酸乙酯、辛酸／癸酸三甘油酯（ GTCC）、丙二醇单辛酸酯（ CAPRYOL 90）中的溶解度为：13．82±0．94μg・ mL －1、43．25±3．76μg・ mL－1、157．1±2．28μg・ mL －1；在乳化剂吐温－85、聚氧乙烯氢化蓖麻油RH（ Cremo－phor－RH）、吐温－80中的溶解度为627．2±24．3μg・ mL－1、693．3±20．6μg・ mL －1、878．7±8．56μg・ mL－1；在助乳化剂聚乙二醇－400（ PEG－400）、1，2－丙二醇、二乙二醇单乙醚（Transcutol P）中的溶解度分别为965．4±0．37μg・ mL－1、858．0±0．91μg・ mL －1、2869．0±0．37μg・ mL －1。盐酸雷洛昔芬自微乳剂组成：盐酸雷诺昔芬、乙酸乙酯、Cremophor－RH40、Transcutol P，优化的处方为盐酸雷洛昔芬5mg，乙酸乙酯0．15g，Cremo－phor－RH400．15g，Transcutol P 0．15g，平均粒径为8．99nm，分散系数为0．377。结论盐酸雷洛昔芬自微乳制备简单，性质稳定，质量易控，有良好的自乳化能力。%OBJECTIVE To study the prescription of raloxifene hydrochloride self-microemulsifying drug deliv-ery system( SMEDDS).METHODS Emulsifying ability of various excipients such as oil,emulsifier,and co-emulsi-fier was screened according to solubility of raloxifene hydrochloride in them.To optimize prescription,orthogonal de-sign was used indexes such as,transmittance,emulsion speed,oil layer and mixed-layered when oil,emulsifier,and co-emulsifier were mixed,and that had the best combination was decided.RESULTS Solubility of raloxifene hydro-chloride in the oil of Ethyl Acetate, GTCC and CAPRYOL 90 was 13.82 ±0.94μg・ mL-1、43.25 ±3.76μg・mL-1、157.1 ±2.28μg・ mL-1 ,respectively,which in the emulsifier of Tween-85,Cremophor-RH 40 and Tween-80 was 627.2 ±24.3μg・ mL-1、693.3 ±20.6μg・ mL-1、878.7 ±8.56μg・ mL-1 ,respectively,and in the co-emulsi-fier of PEG-400 ,1 ,2-propanediol and Transcutol P was 965.4 ±0.37μg・ mL-1、858.0 ±0.91μg・ mL-1、2869.0 ± 0.37μg・ mL-1 ,respectively.The composition of raloxifene hydrochloride self-microemulsifying drug delivery system was:raloxifene hydrochloride,Ethyl Acetate,Cremophor-RH40 and Transcutol P,and the mass was 5mg,0.15g, 0.15g and 0.15g.The average grain diameter was 8.99nm, and the dispersion coefficient was 0.377.CONCLUSION Preparation of raloxifene hydrochloride self-microemulsifying drug delivery system is sam-ple,the quality is easy control and has a good emulsifying capacity.