Molecular, Macromolecular Chemistry, and Materials Laboratory, CNRS, ESPCI-Paris , PSL Research University , 10 Rue Vauquelin , 75005 Paris , France.
Mol Pharm. 2019 Oct 7;16(10):4089-4103. doi: 10.1021/acs.molpharmaceut.9b00601. Epub 2019 Sep 5.
Many pharmaceutical drugs in the marketplace and discovery pipeline suffer from poor aqueous solubility, thereby limiting their effectiveness for oral delivery. The use of an amorphous solid dispersion (ASD), a mixture of an active pharmaceutical ingredient and a polymer excipient, greatly enhances the aqueous dissolution performance of a drug without the need for chemical modification. Although this method is versatile and scalable, deficient understanding of the interactions between drugs and polymers inhibits ASD rational design. This current Review details recent progress in understanding the mechanisms that control ASD performance. In the solid-state, the use of high-resolution theoretical, computational, and experimental tools resolved the influence of drug/polymer phase behavior and dynamics on stability during storage. During dissolution in aqueous media, novel characterization methods revealed that ASDs can form complex nanostructures, which maintain and improve supersaturation of the drug. The studies discussed here illustrate that nanoscale phenomena, which have been directly observed and quantified, strongly affect the stability and bioavailability of ASD systems, and provide a promising direction for optimizing drug/polymer formulations.
市场上和研发管线中的许多药物的水溶性较差，从而限制了其口服给药的效果。使用无定形固体分散体（ASD），即活性药物成分和聚合物赋形剂的混合物，可以大大提高药物的水溶解度，而无需进行化学修饰。尽管这种方法用途广泛且具有可扩展性，但对药物和聚合物之间相互作用的理解不足限制了 ASD 的合理设计。这篇综述详细介绍了理解控制 ASD 性能的机制的最新进展。在固态下，使用高分辨率的理论、计算和实验工具解决了药物/聚合物相行为和动力学对储存期间稳定性的影响。在水介质中的溶解过程中，新的表征方法揭示了 ASD 可以形成复杂的纳米结构，从而维持和提高药物的过饱和度。这里讨论的研究表明，纳米尺度的现象已经被直接观察和量化，这些现象强烈影响 ASD 系统的稳定性和生物利用度，并为优化药物/聚合物配方提供了有希望的方向。
