Ha

Cio the concentration of the species may be written as shown, and therefore the dissociation constant in the aqueous phase, Kw is given by

K is a constant combining the partition coefficient and the association constant. Table 5.16 illustrates the use of equations (5.29) and (5.30).

Partitioning of ionisable species

Being weak electrolytes many drugs will ionise in at least one phase, usually the aqueous

If dimerisation occurs in the organic phase and if Kd is the dissociation constant of dimers into single molecules, we can consider the process in the organic phase to be

organic phase acqueous phase \2

where N is (Cw - Cion), that is, the concentration of unionised molecules in water, the species which will distribute into the non-aqueous phase. It is generally accepted that only the nonionised species partitions from the aqueous phase into the nonaqueous phase. Ionised species, being hydrated and highly soluble in the aqueous phase, disfavour the organic phase. Transfer of such a hydrated species involves dehydration. In addition, organic solvents of low polarity do not favour the existence of free ions.

Equation (5.32) can be rearranged to give

Multiplying by 1/KDN2 obtain and rearranging, we

A plot of Co/N2 against 1/N will yield a straight line with slope P.

If ionisation and its consequences are neglected, an apparent partition coefficient, Papp, is obtained simply by assay of both phases, which will provide information on how much of the drug is present in each phase, regardless of status. The relationship between the true thermodynamic P and Papp is given by the following equations:

For acids:

0 0

Post a comment