Characterization of Solid-State Phase Morphology in Amorphous Solid Dispersions

A common property among drug candidates is poor water solubility, which limits their uptake in the body. In response, an amorphous solid dispersion (ASD) is a pharmaceutical formulation that uses a polymer matrix to kinetically trap amorphous phases of the active pharmaceutical ingredient (API) to improve its solubility and efficacy. They can be formulated as pills or implants, and their dissolution profile is directly related to the morphology of the API-rich phase which is sensitive to both composition and processing conditions of the blends. In this work, we will use SESANS to characterize the degree of phase separation in these materials, understand the mechanism by which the polymer traps amorphous forms of the API, and answer the question: how does ASD phase morphology change as a function of active phase concentration and choice of polymer matrix?

候选药物普遍存在水溶性不佳的问题，这会限制其在体内的吸收。针对该问题，无定形固体分散体（amorphous solid dispersion, ASD）是一类药物制剂，通过聚合物载体动力学捕获活性药物成分（active pharmaceutical ingredient, API）的无定形态，以提升其溶解度与药效。此类制剂可制成片剂或植入剂，其溶出曲线与富API相的微观形貌直接相关，而该形貌同时受共混物的组分比例与制备工艺条件的影响。本研究将采用自旋回波小角中子散射（SESANS）表征此类材料的相分离程度，阐明聚合物捕获API无定形态的作用机制，并解答如下科学问题：无定形固体分散体的相形貌如何随活性相浓度与聚合物载体种类的变化而改变？