Mk. Nair et al., BIOMEMBRANE PERMEATION OF NICOTINE - MECHANISTIC STUDIES WITH PORCINEMUCOSAE AND SKIN, Journal of pharmaceutical sciences, 86(2), 1997, pp. 257-262
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.