注射用难溶药物增溶技术的研究进展

Progress on the Techniques for Enhancing Aqueous Solubility of Water Insoluble Drugs for Parenteral Delivery

活性成分水溶性差是超过40%新药开发失败的主要原因,它不仅会延迟或终止一个重要新药的开发进程,而且使得现有上市产品的剂型改造也变得非常困难。溶解度问题是注射剂中的重要问题之一,在注射用新药开发过程中可以通过不同技术手段进行改善。在解决难溶药物注射剂型问题时,调节pH值、成盐、共溶剂等都是提高难溶药物溶解度的一些常规的重要方法,但每种方法都有其优势和局限性;新技术如纳米悬浮、超临界处理等为难溶药物注射给药系统提供了新的机遇。该综述主要探讨难溶药物注射给药系统的各种增溶技术和方法,以期降低因溶解度问题导致的新化学实体开发成药失败的几率。

Water insolubility is the primary cause for over 40% of failures of drug development,including postponement,or complete termination. Novel drug development,even much-needed reformulation of currently marketed products,can be significantly affected by these challenges. Water solubility is a major issue for injectable formulations. Currently,various approaches,such as pH adjustment,salt formation,co-solvency,have been employed to enhance the solubility of poorly water soluble drugs. However,each strategy exhibits certain advantages and limitations during the pharmaceutical product development. More advanced techniques including nano-suspension,supercritical processing may provide greater opportunities in the preparation of poorly soluble drugs for parenteral delivery systems. The present review is devoted to various techniques for enhancing water solubility of parenteral delivery systems in order to reduce the percentage of poorly water soluble drug candidates eliminated from the development.