Challenges to improve the biopharmaceutical properties of poorly water-soluble drugs and the application of the solid dispersion technology

ABSTRACT The oral solid dosage forms are extremely relevant to drug therapy and responsible for much of the pharmaceutical industry turnover worldwide. However, the development of medicines in solid form involves significant challenges, including obtaining formulations with appropriate bioavailability for low aqueous solubility drugs (classes II and IV of the Biopharmaceutics Classification System). One of the most effective strategies to overcome poor dissolution rate and low absorption of drugs is the solid dispersion technique, however, although it has been the focus of much research in recent decades, there are relatively few commercially available products based on such technology. This is mainly due to problems related to production scale-up and physicochemical instability and creates opportunities for new studies to explore the full potential of the technology. This review presents an overall approach to the factors affecting the dissolution rate and oral bioavailability of BCS-classes II and IV drugs and a brief review of the state-of-theart of solid dispersion technology.

摘要
口服固体制剂与药物治疗息息相关，占据了全球制药行业营收的绝大部分。然而，固体制剂的研发面临诸多严峻挑战，其中包括为低水溶性药物（生物药剂学分类系统（Biopharmaceutics Classification System）的II类与IV类药物）开发具备适宜生物利用度的制剂。
克服药物溶出速率缓慢、体内吸收不足问题的最有效策略之一为固体分散技术。尽管近几十年来该技术始终是诸多研究的焦点，但基于此技术的商业化上市产品却相对稀少。这一现状主要源于生产规模放大与理化不稳定性相关的诸多问题，同时也为探索该技术全部潜力的全新研究创造了机遇。
本综述系统梳理了影响生物药剂学分类系统II类与IV类药物溶出速率及口服生物利用度的各类因素，并简要回顾了固体分散技术的当前研究前沿进展。