Nair M K, Chetty D J, Ho H, Chien Y W
Controlled Drug-Delivery Research Center, Rutgers University, College of Pharmacy, Piscataway, NJ 08854, USA.
J Pharm Sci. 1997 Feb;86(2):257-62. doi: 10.1021/js960095w.
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.
在本研究中，以从家猪新鲜切除的不同皮肤区域和吸收性黏膜为对象，研究了尼古丁的渗透和分配随pH的变化情况。作为一种可电离化合物（pKa值为3.04和7.84），不同pH值溶液中的尼古丁为确定分子电荷状态对渗透的影响提供了一个模型。尼古丁在猪黏膜和皮肤中的渗透遵循零级动力学。渗透速率取决于供体溶液的pH值，并随pH值升高呈指数增加。除鼻黏膜对所有尼古丁种类显示出相似的渗透性外，未电离形式（NN）的尼古丁在各种皮肤和黏膜标本中的渗透性显著高于电离形式（NNH +、NH + NH +）（p < 0.001）。还发现，未电离的尼古丁分子通过吸收性黏膜（鼻、颊、舌下和牙龈）比通过皮肤（腹部、背部、大腿和耳廓）更具渗透性。进行了分配研究，结果进一步证实尼古丁的生物膜渗透遵循pH分配理论。
