Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
J Drug Target. 2010 Dec;18(10):704-31. doi: 10.3109/1061186X.2010.525652. Epub 2010 Oct 26.
The inclusion of certain polymers within solid dispersion or lipid-based formulations can maintain drug supersaturation after dispersion and/or digestion of the vehicle, leading to improvements in bioavailability and variability in exposure. This review presents an overview of the fundamental principles that underpin drug precipitation mechanisms, describes the mechanisms by which precipitation may be inhibited, discusses the methods that can be used to identify polymeric precipitation inhibitors (PPIs), and summarizes current literature evidence of the most effective PPIs. Preliminary data from our laboratory is also presented, which describes the precipitation inhibition behavior of 53 polymeric materials using supersaturated solutions of danazol as a model, poorly water-soluble drug. These studies identify a group of PPIs with superior precipitation inhibition qualities, the majority of which are cellulose-based. These new results in combination with previous published data indicate that PPIs represent an appealing new technology with the potential to improve drug absorption for poorly water-soluble drugs. The molecular determinants of polymer utility, however, remain relatively poorly understood, although the cellulose derivates appear, in general, to provide the most benefit. More detailed studies are therefore required to define the parameters that most effectively predict and quantify the drug-polymer relationships that control precipitation inhibition.
某些聚合物在固体分散体或基于脂质的制剂中的存在可以在载体分散和/或消化后维持药物过饱和状态，从而提高生物利用度和暴露的可变性。本综述介绍了支持药物沉淀机制的基本原理概述，描述了可能抑制沉淀的机制，讨论了可以用来识别聚合物沉淀抑制剂（PPI）的方法，并总结了最有效 PPI 的当前文献证据。我们实验室的初步数据也被提出，该数据描述了使用作为模型的丹那唑过饱和溶液的 53 种聚合物材料的沉淀抑制行为，丹那唑是一种水溶性差的药物。这些研究确定了一组具有卓越沉淀抑制特性的 PPI，其中大多数是基于纤维素的。这些新结果与之前发表的数据表明，PPI 代表了一种有吸引力的新技术，有可能改善水溶性差的药物的药物吸收。然而，聚合物用途的分子决定因素仍然相对了解甚少，尽管纤维素衍生物通常提供最大的益处。因此，需要进行更详细的研究来定义最有效地预测和量化控制沉淀抑制的药物-聚合物关系的参数。
