Abstract：
Supersaturation and precipitation within the gastrointestinal tract can influence oral absorption of active pharmaceutical ingredients (APIs). Supersaturation of weakly basic APIs upon transfer from the stomach into the small intestine may enhance their absorption, while salt forms of poorly soluble weak acids may generate supersaturated solutions in both stomach and intestine. Likewise, APIs with solubility-limited absorption may be developed as enabling formulations intended to produce supersaturated solutions of the API in the gut. Integrating the supersaturation/precipitation characteristics of the API into the biopharmaceutical risk classification enables comprehensive mapping of potential developability risks and guides formulation selection towards optimizing oral bioavailability (BA). The refined Developability Classification System (rDCS) provides an approach for this purpose. In this work, the rDCS strategy is revisited and a stratified approach integrating the in vitro supersaturation and precipitation behavior of APIs and their formulations is proposed.
摘要：
胃肠道内的过饱和和沉淀可影响活性药物成分(API)的口服吸收。从胃转移到小肠时，弱碱性API的过饱和可能会增强其吸收，而可溶性差的弱酸的盐形式可能会在胃和肠道中产生过饱和溶液。同样，具有溶解度限制吸收的API可以被开发为能够在肠道中产生API的过饱和溶液的制剂。将API的过饱和/沉淀特征整合到生物制药风险分类中能够全面绘制潜在可开发性风险并指导制剂选择以优化口服生物利用度(BA)。完善的可开发性分类系统（rDCS）为此提供了一种方法。在这项工作中,重新审视了rDCS策略，并提出了一种分层方法，该方法整合了API及其配方的体外过饱和和沉淀行为。
