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.

中文翻译：

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增强口服药物溶解度和递送的聚合物设计进展

合成聚合物已使无定形固体分散体（ASD）成为口服给药策略，可克服药物在水性环境中的不良溶解性。现代ASD产品可无创地治疗多种慢性疾病（例如，丙型肝炎，囊性纤维化和HIV）。在这样的制剂中，聚合物载体在溶解时产生并维持药物过饱和，从而增加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。在本综述中，我们概述了设计聚合物赋形剂以驱动与喷雾干燥ASD中的活性药物成分（API）相互作用的几种方法，并从工业和学术角度突出了聚合物-药物制剂指南。特别关注可溶解高疏水性API并抑制药物快速重结晶的新的商业化和专业化聚合物设计策略。这些分子定制的赋形剂和分层赋形剂组合有望为早期药物发现开发提供信息，并为我们不断增长的全球人口将现有的API候选药物重新配制为可能挽救生命的口服药物。