期刊
PHARMACEUTICS
卷 14, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14010182
关键词
intestinal permeability; Caco-2; solubility-pH; pKa; BCS; JM-20; MDCK
资金
- Agencia Estatal Investigacion
- European Union through FEDER (Fondo Europeo de Desarrollo Regional) [SAF2016-78756]
The aim of this study was to characterize the biopharmaceutical properties of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20. The results showed that JM-20 had higher solubility at acidic pH but low solubility overall. It also exhibited high permeability and absorption carrier-mediated transport mechanism. Based on the biopharmaceutical classification system, JM-20 was provisionally classified as class 2.
The main aim of this work is the biopharmaceutical characterization of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20, derived with potent anti-ischemic and neuroprotective effects. In this study, the pKa and the pH-solubility profile were experimentally determined. Additionally, effective intestinal permeability was measured using three in vitro epithelial cell lines (MDCK, MDCK-MDR1 and Caco-2) and an in situ closed-loop intestinal perfusion technique. The results indicate that JM-20 is more soluble at acidic pH (9.18 +/- 0.16); however, the Dose number (Do) was greater than 1, suggesting that it is a low-solubility compound. The permeability values obtained with in vitro cell lines as well as with the in situ perfusion method show that JM-20 is a highly permeable compound (Caco-2 value 3.8 x 10(-5)). The presence of an absorption carrier-mediated transport mechanism was also demonstrated, as well as the efflux effect of P-glycoprotein on the permeability values. Finally, JM-20 was provisionally classified as class 2 according to the biopharmaceutical classification system (BCS) due to its high intestinal permeability and low solubility. The potential good oral absorption of this compound could be limited by its solubility.
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