口服控释改良释放剂型的相关发展.ppt

Major Development Impacting Oral Controlled Release Since the 1950’s (continued)自二十世纪五十年代以来影响口服控制剂型的主要发展（续） Greater knowledge on material properties, drug release mechanisms, and physicochemical factors affecting the oral dosage form design and performance 对影响口服剂型设计和性能的材料性质，药物释放原理和物理化学因子的更多认识 Proliferation of novel drug delivery technologies 新型药物释放技术的增加 Major advances in analytical chemistry, instrumentation, computer modeling, process equipment monitoring 分析化学，仪器操作，计算机模型设计，工艺设备监控的主要进步 Future Prospects未来展望 Challenges in Controlled Release Oral Delivery控释口服释放所面临的挑战 Improving Bioavailability of Poorly Soluble Drugs 提高难溶药物的生物利用度 Prolongation of GI Transit Time 延长胃肠道通过时间 Delivery of Peptide and Protein Drugs 肽类和蛋白药物的释放 Approaches to Improve Solubility Rate of Dissolution提高溶解度溶出速度的方法 Particle Size Reduction (↑ surface area) 颗粒尺寸降低（ ↑ 表面积增加） Micronization微粉化 Nanosized Systems纳米系统 Complexation/Solubilization (↑ solubility surface area)络和作用/增溶作用（ ↑ 溶解度 表面积） Surfactants/Self-Emulsifying Systems 表面活性剂/自身乳化系统 Cyclodextrins 环糊精 Molecular Dispersion in Carriers (↑ solubility surface area)载体中的分子分散作用（ ↑溶解度 表面积） Solid Solutions (Coprecipitates) 固溶体（共沉物） Solid Dispersions 固态分散体 Chemical Modification (↑ solubility) 化学修饰（ ↑ 溶解度） Soluble Prodrugs可溶前体药物 Soluble Salts可溶盐 Enabling extended absorption for compounds with absorption window in upper GI tract 对于吸收窗在上胃肠道的化合物能延长吸收窗 Better bioavailability 更好的生物利用度 Potential Benefit: 潜在的优点 Rationale: 原理 To increase gastric residence time for drugs mainly absorbed in the upper GI tract 为了增加主要在上胃肠道吸收药物的胃部停留时间 Proposed Approaches: 推荐方法 Floating dosage forms 漂浮剂型 Expanding dosage 增加剂量 High density pellets 高密度小丸 Bioadhesives 生物粘附 - Co-administration of drugs which delay gastric emptying 一起给与延迟胃排空药物 Challenges: 挑战 - Reproducibility 重现性 - Conclusive evidence of clinical benefit is lacking 缺少利于临床的明显证据(参考 Waterman, Pharm. Dev. Tech., 12: 1-10, 2007) Gastroretentive Dosage Forms 胃部滞留剂型 Products: Glumetza (Metformin) Ma