Bioconjug Chem. 2018 Apr 18;29(4):939-952. doi: 10.1021/acs.bioconjchem.7b00646. Epub 2018 Jan 10.
Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.
合成聚合物使无定形固体分散体（ASD）成为一种口服递送策略，用于克服在水介质环境中药物溶解度差的问题。现代 ASD 产品非侵入性地治疗一系列慢性疾病（例如，丙型肝炎、囊性纤维化和 HIV）。在这些配方中，聚合物载体在溶解时产生并维持药物过饱和，从而提高表观药物溶解度以增强胃肠道屏障吸收和口服生物利用度。在这篇综述中，我们概述了几种设计聚合物辅料的方法，以促进喷雾干燥 ASD 中与活性药物成分（API）的相互作用，从工业和学术角度突出了聚合物-药物配方的指导原则。特别关注新的商业和专用聚合物设计策略，这些策略可以溶解高疏水性 API 并抑制药物快速重结晶的趋势。这些分子定制的赋形剂和分层赋形剂组件有望为我们不断增长的全球人口提供有希望的信息，用于早期药物发现开发和将现有 API 候选物重新配方为潜在的救命口服药物。
