Figure 7.38 Log unstirred water permeabilities versus log molecular weights, based on analysis of iso-pH data.

to the partition coefficients, octanol-water provided the octanol-water system is a suitable model for the phospholipid system. Ideally, a plot of log P0 versus log would represent case (a) in Fig. 7.19. For permeability data uncorrected for UWL effects, a case (b) relationship would be expected. The case (c) pattern in Fig. 7.19 would be expected if water pore transport were an available mechanism in PAMPA. Figure 7.39, showing log P0 (Table 7.10) versus log(Table 7.4), indicates that the relationship is approximately linear (r2 0.79) over eight orders of magnitude of permeability, suggesting the absence of water pores. Iso-pH Permeability Measurements using Soy Lecithin-Dodecane-Impregnated Filters

The above iso-pH measurements are based on the 2% DOPC/dodecane system (model 1.0 over pH 3-10 range). Another membrane model was also explored by us. Table 7.16 lists iso-pH effective permeability measurements using the soy lecithin (20% wt/vol in dodecane) membrane PAMPA (models 17.1, 24.1, and 25.1) The negative membrane charge, the multicomponent phospholipid mixture, and the acceptor sink condition (Table 7.1) result in different intrinsic permeabilities for the probe molecules. Figure 7.40 shows the relationship between the 2% DOPC and the 20% soy iso-pH PAMPA systems for ketoprofen. Since the intrinsic permeability of ketoprofen in the soy lecithin membrane is about 20 times greater than in DOPC membrane, the flat diffusion-limited transport region of the log Pe log Po (2% DOPC) vs Oct-Water log Kp

0 0

Post a comment