唐景玲纳米技术改善难溶性药物口服吸收讲解课件.ppt

The Stages of Drug Discovery and Development Oral drug absorption Dosage Form Development Strategies A few common strategies to overcome impacts of low solubility on product development: – Salt formation or prodrug – Cyclodextrin inclusion – Solid dispersion – Particle size reduction – Lipid-based drug delivery Particle size reduction Particle size reduction—Patent Nanocrystal technology —Elan corporation The new formulation overcame the drug’s relative insolubility by reducing the particle size to less than 200nm, and subsequently coating the active compound with GRAS (Generally Regarded As Safe) surface stabilizers. Particle size reduction—Patent Dissocubes —Skyepharma Nanoedge —Baxter aqueous media Nanopure —Pharmasol GmbH non-aqueous media (PEG) or water-ethanol mixtures, isotonic water-glycerol mixtures Controlled-flow cavitation (CFC) —Five Star technologies Particle size reduction—Patent Crititech —Crititech Inc. and Lawronce KS Particle Formation Using Supercritical Carbon Dioxide Particle size reduction—Limitations and Future challenges More suitable for the drug of BCS Ⅱ Nanoparticles aggregation during the storage Shortage of the equipment for formulation optimization Shortage of the methods for in vitro evaluation for nanoparticles Definition of Lipid-baseddelivery systems The Lipid Formulation Classification System 上市剂型 提高难溶性有效成分的溶出度 新剂型优点 提高口服生物利用度 工艺简单 、服用方便 本课题的研究将为大量有前景的难溶性药物， 特别是难溶性中药口服制剂的研究提供参考 五仁醇（五味子乙醇提取物） 五仁醇主要成分溶解度的测定 药物溶解度在辅料中得到了极大提高 通过观察溶解后溶液的颜色及外观来判断溶解的程度 209倍 36倍 7倍 41倍 172倍 31倍 106倍 18倍 伪三元相图的绘制 油酸：5%~35% 吐温20：60%~70% Transcutolp：5%~25% 均一、透明，略有乳光. 五仁醇自乳化制剂最终处方的确定及制备 处方 400 粒 Total 150 Transcutol P 650 吐温20 200 油酸 200 五仁醇 Quality (g) Formulation 制备方法 混匀后的辅料 五仁醇 ＋ 40 °C温度以内 超声完全混合 药物完全溶解 装胶囊 五仁醇自乳化制剂与市售胶囊的含量测定 自乳化制剂中五味子醇甲的含量低于市售制剂，五味子乙素的含量高于市售制剂 含药乳液平均粒径为241 nm，粒度分布较均匀 五仁醇自乳化制剂粒度测定： 2.212±0.048 0.9