BIOMEMBRANE PERMEATION OF NICOTINE - MECHANISTIC STUDIES WITH PORCINEMUCOSAE AND SKIN

In the present study, the permeation and partitioning of nicotine as a function of pH was investigated with various regions of skin and abso rptive mucosae that were freshly excised from domestic pigs. As an ion izable compound (pK(a) values of 3.04 and 7.84), nicotine in solutions of different pH values provides a model for determining the influence of the charge status of a molecule on permeation. The permeation of n icotine across porcine mucosae and skin followed zero-order kinetics. The rate of permeation was dependent on donor solution pH and increase d exponentially as the pH increased. With an exception of the nasal mu cosa, which showed similar permneabilities for all species of nicotine , the permeability of nicotine across various skin and mucosal specime ns was significantly higher (p < 0.001) for the un-ionized species (NN ) than for the ionized species (NNH+, NH+NH+). It was also seen that u n-ionized nicotine molecules were more permeable through absorptive mu cosae (nasal, buccal, sublingual, and gingival) than through skin (abd ominal, dorsal, thigh, and ear pinna). Partition studies were performe d and the results further confirmed that biomembrane permeation of nic otine follows the pH-partition theory.