Ionic-species Transport in PAMPA

In all three frames of Fig. 3.4, there is evidence of ionic-species transport, labeled as log Pi in Fig. 3.4. The pH at the bend in the curves corresponding to the onset of ionic permeability is labeled pK and corresponds to the pH where 50% of the transport is by the neutral species and 50% by the ionic species. This is a conditional constant, but unlike and pJ it is dependent mainly on the con- 

In the BBB-PAMPA lipid formulation illustrated in Fig. 3.4, the diff values, defined as the difference log Pq-log Pi, range from 2.9 (morphine) to 4.2 (warfarin), somewhat similar to the values observed in the octanol-water system. However, it is premature to propose a pdiffi-A approximation, given the limited amount of data reported. With other lipid formulations, larger differences are usually observed. In Double-Sink PAM PA, and especially in hexadecane-PAMPA, transport of ionized drugs has not been reported [84]. 

This chapter considered ionizable drug-like molecules. Absorption properties that are influenced by the pKj were explored. The impact of the pKj-absorption relationship on key physicochemical profiling underlying absorption (solubihty, per-meabihty and ionization) was examined in detail and several simpUfying equations were discussed. The various diff relationships considered in the chapter are systematized in Table 3.2. Table 3.3 summarizes the apparent pfQ shift method for detecting aggregates in solubility profiles, when the apparent pff value derived from Henderson-Hasselbalch analysis of log S pH profile does not agree with the 

1 Approximate values in solutions containing 0.15 M ionic strength. Lower value refers to bases and higher value to adds. 

1 Wells, J. I. Pharmaceutical Preformulation, Ellis Horwood, London, 1988. 

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