Abstract：
Polymeric amorphous solid dispersion (ASD) is a popular approach for enhancing the solubility of poorly water-soluble drugs. However, achieving both physical stability and dissolution performance in an ASD prepared with a single polymer can be challenging. Therefore, a secondary excipient can be added. In this paper, we review three classes of additives that can be added internally to ASDs: (i) a second polymer, to form a ternary drug-polymer-polymer ASD, (ii) counterions, to facilitate in situ salt formation, and (iii) surfactants. In an ASD prepared with a combination of polymers, each polymer exerts a unique function, such as a stabilizer in the solid state and a crystallization inhibitor during dissolution. In situ salt formation in ASD usually leads to substantial increases in the glass transition temperature, contributing to improved physical stability. Surfactants can enhance the wettability of ASD particles, thereby promoting rapid drug release. However, their potential adverse effects on physical stability and dissolution, resulting from enhanced molecular mobility and competitive molecular interaction with the polymer, respectively, warrant careful consideration. Finally, we discuss the impact of magnesium stearate and inorganic salts, excipients added externally upon downstream processing, on the solid-state stability as well as the dissolution of ASD tablets.
摘要：
聚合物无定形固体分散体(ASD)是用于增强水溶性差的药物的溶解度的流行方法。然而,在用单一聚合物制备的ASD中实现物理稳定性和溶解性能可能是具有挑战性的。因此,可以添加第二赋形剂。在本文中,我们回顾了三类可以在内部添加到ASD中的添加剂：(I)第二种聚合物，形成三元药物-聚合物-聚合物ASD，(ii)抗衡离子，为了促进原位盐的形成，和(iii)表面活性剂。在用聚合物组合制备的ASD中，每种聚合物都发挥着独特的功能，例如固态稳定剂和溶解期间的结晶抑制剂。ASD中的原位盐形成通常导致玻璃化转变温度的大幅增加，有助于提高物理稳定性。表面活性剂可以增强ASD颗粒的润湿性，从而促进药物的快速释放。然而,它们对物理稳定性和溶解的潜在不利影响，由于增强的分子迁移率和与聚合物的竞争性分子相互作用，分别,值得仔细考虑。最后,我们讨论了硬脂酸镁和无机盐的影响，在下游加工时外部添加的赋形剂，ASD片剂的固态稳定性和溶出度。
