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

Although sublingual captopril has been used clinically to treat hypertensiv e emergencies, a mechanistic understanding of sublingual permeation will fa cilitate the optimization of drug delivery. A correlation of sublingual ste ady-state flux with donor captopril concentration in a porcine model showed the absence of saturability and suggested a passive diffusion permeation m echanism. A simultaneous evaluation of permeability and partition coefficie nt demonstrated that the paracellular route is the predominant pathway for sublingual permeation. The enhancement factors of specific ion permeabiliti es in the presence of tight junction perturbants indicated that although th e paracellular pathway is preferred by the ionized species of captopril, th e lipophilic transcellular pathway is preferred by the neutral, un-ionized species. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Associat ion.