设计具备最佳物理稳定性、溶出表现、和生物利用度的无定形固体分散体.pdf

Design amorphous solid dispersions with optimal physical stability, dissolution performance, and in vivo bioavailability 设计具备最佳物理稳定性、溶出表现、和生物 利用度的无定形固体分散体 1 纲要 Amorphous solid dispersion (ASD) 的行业、 技术背景  开发ASD制剂必须了解的一些关键风险  总结 2 越来越多的难溶药物和相应的制剂挑战 Why there are so many BCSII/IV drugs?  Increased structure complexity of drug targets (e.g., protein-protein interaction)  Combinatory chemistry and HTS  Biological activity remains as the first Sherry Ku, 2010 Improving solubility priorit Conference, based on 100 NCE More difficult to meet product requirements with conventional technologies (salt formation, particle size reduction, co-solvency, etc.):  Bioavailabilit  Patient compliance  pH/food effect, variabilit  Stability, clinical supply, etc. Biopharmaceutics Classification System: The Scientific Basis for Biowaiver Extensions 3 Lawrence X. Yu, Gordon L. Amidon, et al, Pharmaceutical Research; Vol. 19 Number 7, Jul 2002 Recent ASD examples: Kaletra, Regorafenib, Posaconazole, Ledipasvir 4 为什么用无定形药物？ Ritonavir (Abbott): a low solubility, low For example, for fel