Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)

• Published in: AAPS PharmSciTech Vol. 12; no. 2; pp. 573 - 578
• Main Authors: Alvarez-Figueroa, M. Javiera, Pessoa-Mahana, C. David, Palavecino-González, M. Elisa, Mella-Raipán, Jaime, Espinosa-Bustos, Cristián, Lagos-Muñoz, Manuel E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2011
• Subjects: Animals; Animals, Newborn; Benzimidazoles - classification; Benzimidazoles - pharmacokinetics; Benzimidazoles - standards; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biopharmaceutics - methods; Biopharmaceutics - standards; Biotechnology; Cannabinoids - classification; Cannabinoids - pharmacokinetics; Cannabinoids - standards; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Drug Evaluation, Preclinical - methods; Drug Evaluation, Preclinical - standards; Indexing in process; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Membranes, Artificial; Pharmacology/Toxicology; Pharmacy; Predictive Value of Tests; Research Article; Skin Absorption - drug effects; Skin Absorption - physiology; Swine; benzimidazole; BCS; PAMPA; transdermal penetration
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-011-9622-1

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P oct value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).