Temporally controlled drug delivery systems: coupling of pH oscillators with membrane diffusion

A novel approach to modulate the release of a drug or an active ingredient that avoids the need for external power sources or electronic controllers is described. By changing the pH of a solution relative to the pKa, a drug, enhancer, or solubilizer may be rendered charged or uncharged. Because only the uncharged form of a drug can permeate across lipophilic membranes, a temporally modulated delivery profile may be obtained with a pH oscillator in the donor solution. Ionizable permeants have a buffer capacity, so the feasibility of coupling the mixed Landoldt pH oscillator with membrane diffusion of nicotine or benzoic acid is demonstrated for a single oscillation.