PH, pK(a) and dermal delivery

The effect of pH on the permeation of ibuprofen and lignocaine through huma n skill has been modelled using a modification to the equation derived by P otts and Guy, which is normally applied to unionized entities. The results show that permeation is related to the distribution coefficient. The physic ochemical properties have been predicted ab initio using commercially avail able software and compared to literature values. The approach is successful and shows that there is significant permeation of the ionized drugs throug h a lipophilic pathway, possibly as a result of ion pairing. Since the aque ous solubility of the ionized material is significantly higher than the uni onized, the maximum flux through the skill may occur at a pll where ionizat ion is high. Optimum topical or transdermal formulations may not therefore be for the free acid or free base. (C) 2000 Elsevier Science B.V. All right s reserved.