Partition profiles

Reymond,F. Steyaert,G. Carrupt, P.-A. Morin, D. Tillement,J.P. Girault,H. Testa,B., The pH-partition profile of the anti-ischemic drug trimetazidine may explain its reduction of intracellular acidosis, Pharm. Rese. 16, 616-624 (1999). 

Caron, G. Pagliara, A. Gaillard, P. Carrupt, P-A. Testa, B., Ionization and partitioning profiles of zwitterions The case of the anti-inflammatory drug azapropazone, Helv. Chim. Acta. 79, 1683-1695 (1996). 

Figure 7. Lipophilicity profile of propranolol in liposomes composed of zwitterionic and charged lipids (phosphatidyl ethanolamine (PE), oleic acid (OA), phosphatidyl inositol (PI)). Conditions of measurements are described in [113]. The dotted line indicates the partitioning profile of propranolol in the egg PC liposome system. The bars show the pH-dependent charge profile of propranolol (hatched bars positively charged propranolol) and the lipids in the membrane (black bars negatively charged lipids). Reprinted from [113] Kramer, S. (2001). Liposome/water partitioning , In Pharmacokinetic Optimization in Drug Research, eds. Testa, B. et al. Reproduced by permission of Verlag Helvetica Chimica Acta, Zurich...

Figure7.25 The pH-partition profiles of PGE, between soybean oil and water at 20°C, explaining why the release profiles have the pH dependency shown in Fig. 7.24.

Figure 21 Sigmoidal pH partition profile of an acid AH. Log P pp (= log D) is constant at low pH values (log = log P ), decreases witlj increasing pH values (P,pp = 0.5P at pH = pKJ with a slope = 1 and reaches again a constant value at log P pp = log Pj (reproduced from Figure 2 of ref. [220] with permission from the copyright owner).

Figure 22 pH Partition profile of propranolol (16) calculated from measured values pK = 9.72, log P = 3.41, and log Pi = 0.48 (reproduced from Figure 3 of ref. [463] with permission from the American Pharmaceutical Association, Washington, DC, USA). 

Deviations from the simple pH partition hypothesis (i.e. the pH absorption profiles should be parallel to pH partition profiles) (e.g. [473, 474]), called pH shift, are obtained for highly lipophilic compounds their absorption profiles are shifted to higher (acids) and lower (bases) pH values (Figure 27). The higher the lipophilicity of the neutral species is, the higher is the observed pH shift. 

The above terms are applicable when the concentrations of the ionized species in the organic phase are negligible and the ambient pH is relatively close to the respective values. The pH partition profiles take the form of a sigmoidal curve (Figure 1.7). 

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