Introduction: Given that hydrophobic active pharmaceutical ingredients (APIs) intended for oral delivery comprised about 68% of US FDA approvals in 2019 alone, the impact of endogenous gastrointestinal (GI) molecules on their inherently unstable solution behavior needs to be elucidated.Areas covered: The interactions between hydrophobic API's and GI phospholipids, bile acids/salts and digestive proteins are explored. The impact of the complex relationship between the GI molecules and hydrophobic APIs on solubilization by micelle formation, complexation or by inhibiting the nucleation of high energy forms of hydrophobic APIs, so called supersaturating drug delivery systems is complex. The ability of these endogenous GI molecules to manipulate the solution behavior of hydrophobic APIs has been demonstrated both at their native concentrations and when included as exogenous formulation additives. Specific studies of the impact of proteins and mixed micelles on solubilization and crystallization are reported.Expert opinion: Elucidation of the complex molecular interactions between orally administered hydrophobic APIs and endogenous GI molecules will enable better in vivo/in vitro correlation and potentially lead to formulation strategies that avoid the stochastic nature of hydrophobic API precipitation in the GI tract.

中文翻译：

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内源性胃肠道分子对口服递送的疏水性API的溶解和沉淀的影响。

简介：鉴于仅用于口服的疏水性活性药物成分（API）仅在2019年就占美国FDA批准的68％，因此需要阐明内源性胃肠道（GI）分子对其固有的不稳定溶液行为的影响。探索了疏水性API和GI磷脂，胆汁酸/盐和消化蛋白之间的相互作用。GI分子和疏水性API之间的复杂关系通过胶束的形成，复合或通过抑制疏水性API的高能形式的成核作用对增溶的影响是复杂的，因此所谓的过饱和药物传递系统非常复杂。这些内源性GI分子操纵疏水性API溶液行为的能力已在其天然浓度和作为外源制剂添加剂被证明时得到了证明。报道了蛋白质和混合胶束对溶解和结晶的影响的具体研究专家意见：阐明口服疏水性API与内源性GI分子之间复杂的分子相互作用将使体内/体外更好的相关性成为可能，并可能导致制定制剂策略避免了胃肠道中疏水性API沉淀的随机性。