In Vitro Oral Cavity Permeability Assessment to Enable Simulation of Drug Absorption

作者：Pankaj Dwivedi, Priyata Kalra, Haiying Zhou, Khondoker Alam, Eleftheria Tsakalozou, Manar Al-Ghabeish, Megan N. Kelchen, Giovanni M. Pauletti · 发表于：Pharmaceutics · 年份：2025 · DOI：10.3390/pharmaceutics17070924 · 被引用次数：3 · 研究领域：Drug Transport and Resistance Mechanisms、Advanced Drug Delivery Systems、Drug Solubulity and Delivery Systems

Background/Objectives: The oral cavity represents a convenient route of administration for drugs that exhibit significant hepatic first-pass extraction. In this study, the mucosal permeation properties of selected active pharmaceutical ingredients (APIs) incorporated into oral cavity drug products that are approved by the U.S. Food and Drug Administration were quantified using the human-derived sublingual HO-1-u-1 and buccal EpiOral™ in vitro tissue models. Methods: Epithelial barrier properties were monitored using propranolol and Lucifer Yellow as prototypic transcellular and paracellular markers. APIs were dissolved in artificial saliva, pH 6.7, and transepithelial flux from the apical to the basolateral compartment was quantified using HPLC. Results: Apparent permeability coefficients (Papp) calculated for these APIs in the sublingual HO-1-u-1 tissue model varied from Papp = 2.72 ± 0.06 × 10−5 cm/s for asenapine to Papp = 6.21 ± 2.60 × 10−5 cm/s for naloxone. In contrast, the buccal EpiOral™ tissue model demonstrated greater discrimination power in terms of permeation properties for the same APIs, with values ranging from Papp = 3.31 ± 0.83 × 10−7 cm/s for acyclovir to Papp = 2.56 ± 0.68 × 10−5 cm/s for sufentanil. The tissue-associated dose fraction recovered at the end of the transport experiment was significantly increased in the buccal EpiOral™ tissue model, reaching up to 8.5% for sufentanil. Conclusions: Experimental permeation data collected for selected APIs in FD...