A major parameter controlling the extent and rate of oral drug absorption is permeability through the lipid bilayer of intestinal epithelial cells. Here, a biomimetic artificial membrane permeability assay (Franz–PAMPA Pampa) was validated using a Franz cells apparatus. Both high and low permeability drugs (metoprolol and mannitol, respectively) were used as external standards. Biomimetic properties of Franz–PAMPA were also characterized by electron paramagnetic resonance spectroscopy (EPR). Moreover, the permeation profile for eight Biopharmaceutic Classification System (BCS) model drugs cited in the FDA guidance and another six drugs (acyclovir, cimetidine, diclofenac, ibuprofen, piroxicam, and trimethoprim) were measured across Franz–PAMPA. Apparent permeability (Papp) Franz–PAMPA values were correlated with fraction of dose absorbed in humans (Fa%) from the literature. Papp in Caco-2 cells and Corti artificial membrane were likewise compared to Fa% to assess Franz–PAMPA performance. Mannitol and metoprolol Papp values across Franz–PAMPA were lower (3.20 × 10⁻⁷ and 1.61 × 10⁻⁵ cm/s, respectively) than those obtained across non-impregnated membrane (2.27 × 10⁻⁵ and 2.55 × 10⁻⁵ cm/s, respectively), confirming lipidic barrier resistivity. Performance of the Franz cell permeation apparatus using an artificial membrane showed acceptable log-linear correlation (R² = 0.664) with Fa%, as seen for Papp in Caco-2 cells (R² = 0.805). Data support the validation of the Franz–PAMPA method for use during the drug discovery process.

中文翻译：

---

使用BCS模型药物在Franz细胞仪器上进行仿生人工膜通透性测定

控制口服药物吸收程度和速率的主要参数是通过肠上皮细胞脂质双层的渗透性。在这里，使用Franz细胞仪验证了仿生人工膜通透性测定法（Franz-PAMPA Pampa）。高渗透性和低渗透性药物（分别为美托洛尔和甘露醇）均用作外标。Franz–PAMPA的仿生特性还通过电子顺磁共振波谱（EPR）进行了表征。此外，在整个Franz-PAMPA中测量了FDA指南中引用的八种生物制药分类系统（BCS）模型药物和另外六种药物（阿昔洛韦，西咪替丁，双氯芬酸，布洛芬，吡罗昔康和甲氧苄啶）的渗透曲线。表观渗透率（Papp）Franz–PAMPA值与文献中人体吸收的剂量分数（Fa％）相关。同样将Caco-2细胞和Corti人造膜中的Papp与Fa％相比较，以评估Franz-PAMPA的性能。Franz–PAMPA中的甘露醇和美托洛尔Papp值较低（3.20×10比在非浸渍膜上分别得到的值（分别为^-7和1.61×10 ^-5 cm / s）（分别为2.27×10 ^-5和2.55×10 ^-5 cm / s）证实了脂质屏障的电阻率。如对Caco-2细胞中的Papp所见（R ²＝ 0.805），使用人造膜的Franz细胞渗透装置的性能显示具有Fa％的可接受的对数线性相关性（R ²＝ 0.664 ）。数据支持在药物开发过程中使用Franz-PAMPA方法的验证。