Characterization of captopril sublingual permeation: determination of preferred routes and mechanisms

Although sublingual captopril has been used clinically to treat hypertensive emergencies, a mechanistic understanding of sublingual permeation will facilitate the optimization of drug delivery. A correlation of sublingual steady-state flux with donor captopril concentration in a porcine model showed the absence of saturability and suggested a passive diffusion permeation mechanism. A simultaneous evaluation of permeability and partition coefficient demonstrated that the paracellular route is the predominant pathway for sublingual permeation. The enhancement factors of specific ion permeabilities in the presence of tight junction perturbants indicated that although the paracellular pathway is preferred by the ionized species of captopril, the lipophilic transcellular pathway is preferred by the neutral, un-ionized species.