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In the present study, the permeation and partitioning of nicotine as a function of pH was investigated with various regions of skin and absorptive mucosae that were freshly excised from domestic pigs. As an ionizable compound (pKa 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 nicotine across porcine mucosae and skin followed zero-order kinetics. The rate of permeation was dependent on donor solution pH and increased exponentially as the pH increased. With an exception of the nasal mucosa, which showed similar permeabilities for all species of nicotine, the permeability of nicotine across various skin and mucosal specimens 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 un-ionized nicotine molecules were more permeable through absorptive mucosae (nasal, buccal, sublingual, and gingival) than through skin (abdominal, dorsal, thigh, and ear pinna). Partition studies were performed and the results further confirmed that biomembrane permeation of nicotine follows the pH-partition theory.

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This study has shown that formulation variables can be exploited in order to enhance the incorporation of a water soluble drug into chitosan microspheres using the ionotropic gelation technique. Based on a comparison of all results obtained with the different approaches, the modification of the aqueous phase to pH 6 was identified as the most feasible approach.