Optimized conditions of bio-mimetic artificial membrane permeation assay

Effects of pH and co-solvents on the bio-mimetic artificial membrane permea tion assay were investigated to determine the optimal conditions for the pr ediction of oral absorption. The permeability (P-am) of 33 structurally div erse drugs to the PC/PE/PS,PI/CHO/1,7-octadiene membrane system (bio-mimeti c lipid (BML) membrane) was measured at pH 5.5, 6.5. and 7.4. The pH depend ence of P-am was in accordance with the pH partition theory. The better pre diction of oral absorption (fraction of a dose absorbed) was shown under th e pH 5.5 condition (r = 0.866, n = 25) and/or pH 6.5 (r = 0.865, n = 28), r ather than pH 7.4 (r = 0.767, n = 24). Then, the appropriate conditions for determining the permeability of poorly soluble compounds were examined, Di methysulfoxide (DMSO). ethanol (EtOH) and polyoxyethyleneglycol 400 (PEG 40 0) were added up to 30%,, to the transport medium as solubilizers. DMSO. Et OH and PEG 400 decreased P-am. of hydrocortisone and propranolol. For examp le, DMSO (30%,) decreased P-am of hydrocortisone by 60% and by 70% in the c ase of propranolol. DMSO and PEG 400 also decreased P-am of ketoprofen, fit contrast. EtOH produced an opposite effect on permeability, i.e. an increa sed P-am of ketoprofen. Therefore. the high concentration of these co-solve nts could lead to the under- or overestimation of drug permeability. (C) 20 01 Elsevier Science B.V. All rights reserved.