The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.

中文翻译：

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生物相关溶出介质中水溶性差的化合物的固有溶出率分析。

活性药物成分（API）的固有溶出度（IDR）是有助于早期药物开发的关键属性，尤其是选择制剂策略以改善溶出度，从而改善肠道中的药物吸收。在这里，我们开发了一种用于IDR的快速，中等通量筛选的可靠方法，并建立了迄今为止开放文献中最大的IDR数据集，该数据集可用于药物计算模型。在禁食和进食状态的模拟肠液中研究了十八种具有多种理化性质的化合物。使用化合物悬浮液或圆盘，在小规模实验分析中测量溶出度。IDR测量不仅与两种溶解介质中的API溶解度相关。