School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, 422C Mellon Hall, Pittsburgh, PA, 15282, USA.
Pharm Res. 2023 Dec;40(12):2963-2981. doi: 10.1007/s11095-023-03547-4. Epub 2023 Jun 30.
Amorphous solid dispersions (ASDs) are a formulation and development strategy that can be used to increase the apparent aqueous solubility of poorly water-soluble drugs. Their implementation, however, can be hindered by destabilization of the amorphous form, as the drug recrystallizes from its metastable state. Factors such as the drug-polymer solubility, miscibility, mobility, and nucleation/crystal growth rates are all known to impact the physical stability of an ASD. Non-covalent interactions (NCI) between the drug and polymer have also been widely reported to influence product shelf-life. In this review, the relationship between thermodynamic/kinetic factors and adhesive NCI is assessed. Various types of NCIs reported to stabilize ASDs are described, and their role in affecting physical stability is examined. Finally, NCIs that have not yet been widely explored in ASD formulations, but may potentially impact their physical stability are also briefly described. This review aims to stimulate further theoretical and practical exploration of various NCIs and their applications in ASD formulations in the future.
无定形固体分散体 (ASD) 是一种制剂和开发策略，可用于提高水溶性差的药物的表观水溶性。然而，由于药物从亚稳定状态重结晶，无定形形式的不稳定性可能会阻碍其实施。众所周知，药物-聚合物的溶解度、混溶性、迁移率和成核/晶体生长速率等因素都会影响 ASD 的物理稳定性。药物和聚合物之间的非共价相互作用 (NCI) 也被广泛报道会影响产品的保质期。在这篇综述中，评估了热力学/动力学因素与粘性 NCI 之间的关系。描述了各种类型的 NCI 被报道用于稳定 ASD，研究了它们在影响物理稳定性方面的作用。最后，还简要描述了在 ASD 制剂中尚未广泛探索但可能影响其物理稳定性的 NCI。本综述旨在激发对各种 NCI 的进一步理论和实践探索，以及它们在未来 ASD 制剂中的应用。
