High throughput prediction of oral absorption: Improvement of the composition of the lipid solution used in parallel artificial membrane permeation assay

The purpose of the present study was to improve the composition of the lipi d solution used in parallel artificial membrane permeation assay for the pr ecise prediction of coral absorption. We modified the composition of lipid solution, which was used to make a lipid membrane on the filter support. Fi rst, we changed the chain length of organic solvent (PC/alkyldienes [C7-C10 ]), A negative charge was then added to the membrane to mimic the intestina l membrane (PC/stearic acid/1,7-octadiene and PC/PE/PS/PI/cholesterol/1,7-o ctadiene). Finally, we examined the predictability of the PC/PE/PS/PI/CHO/1 ,7-octadiene membrane using structurally diverse compounds. Permeability co efficients of tested compounds were increased as the chain length of alkyld iene became shorter. The addition of a negative charge to the membrane incr eased the permeability of the basic compounds. However, the negatively char ged membrane with stearic acid showed different permeability profiles from PC/PE/PS/PI/CHO. The predictability of the PC/PE/PS/PI/CHO/1,7-octadiene me mbrane was adequate (r = 0.858, n = 31) for use during the early stages of the drug discovery/development process.