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. Author manuscript; available in PMC: 2012 Feb 1.

Published in final edited form as: Pharm Res. 2010 Oct 14;28(2):337–363. doi: 10.1007/s11095-010-0280-x

Fig. 1 — The log permeability vs. pH plots of four of the 108 molecules determined by the PAMPA-BBB method. The a–d frames are based on 3 μL PBLE lipid coated filters, while the e–h frames are based on the 1 μL 4%w/v DOPC in hexadecane BD pre-coated filter plates. The pH was varied to assess the contribution of the aqueous boundary layer and the shunting effect of the paramembrane aqueous pores. The best-fit of the log form of Eq. 1 to the measured effective permeability data, P_e vs. pH, are represented by the solid curves, and the paramembrane- and ABL-corrected log P_m vs. pH curves are represented by dashed curves. The dot curves correspond to the log P_ABL values, and the dot-dash curves correspond to the paramembrane permeability, log P_para. The maximum point in the log P_m curves corresponds to the intrinsic permeability coefficient, log P_o, which characterizes the permeability of the neutral form of an ionizable molecule. The intersections of the horizontal and the diagonal tangents occur at pH values corresponding to the pK_a in the dashed curves. The dynamic range window, DRW, is the permeability gap defined by log P_ABL at the top and log P_para at the bottom.

Fig. 1 — The log permeability vs. pH plots of four of the 108 molecules determined by the PAMPA-BBB method. The a–d frames are based on 3 μL PBLE lipid coated filters, while the e–h frames are based on the 1 μL 4%w/v DOPC in hexadecane BD pre-coated filter plates. The pH was varied to assess the contribution of the aqueous boundary layer and the shunting effect of the paramembrane aqueous pores. The best-fit of the log form of Eq. 1 to the measured effective permeability data, P_e vs. pH, are represented by the solid curves, and the paramembrane- and ABL-corrected log P_m vs. pH curves are represented by dashed curves. The dot curves correspond to the log P_ABL values, and the dot-dash curves correspond to the paramembrane permeability, log P_para. The maximum point in the log P_m curves corresponds to the intrinsic permeability coefficient, log P_o, which characterizes the permeability of the neutral form of an ionizable molecule. The intersections of the horizontal and the diagonal tangents occur at pH values corresponding to the pK_a in the dashed curves. The dynamic range window, DRW, is the permeability gap defined by log P_ABL at the top and log P_para at the bottom.