Harada S, Takahashi Y, Nakagawa H, Yamashita F, Hashida M
Pharmaceutical Engineering Department, Manufacturing & Technology Division, Nippon Orgatnon K.K., Osaka, Japan.
Biol Pharm Bull. 2000 Oct;23(10):1224-8. doi: 10.1248/bpb.23.1224.
We investigated sorption and permeation of emedastine with 11 different vehicles, composed of single or binary solvents, in excised rat skin. In the sorption study, partition parameters of the drug with each vehicle were obtained by dividing the drug amount in skin at equilibrium by its donor concentration. When the logarithm of the partition parameters for the stratum corneum/vehicle partitioning (Ks') was plotted against the dielectric constants of the vehicles, a bi-linear relationship was obtained. The skin flux of emedastine largely differ among the vehicles. A quasi-steady-state flux of emedastine exhibited a good linear relationship with Ks', except for ethanol (EtOH)/isopropyl myristate (IPM) systems, indicating that the partitioning process is critical in determining the permeation rate. Delineation of the EtOH/IPM systems would be due to an increase in the diffusivity of the drug in the stratum corneum, as indicated by the analysis using a two-layer diffusion model. Thus, differential evaluation of partitioning and diffusion processes by both sorption and permeation studies would give further insights into the effects of vehicles on skin permeation of drugs.
我们研究了依美斯汀在由单一或二元溶剂组成的11种不同载体中的吸附和渗透情况，实验对象为切除的大鼠皮肤。在吸附研究中，通过将皮肤中药物在平衡时的量除以其供体浓度，获得药物与每种载体的分配参数。当角质层/载体分配（Ks'）的分配参数对数与载体的介电常数作图时，得到了双线性关系。依美斯汀在不同载体中的皮肤通量差异很大。除乙醇（EtOH）/肉豆蔻酸异丙酯（IPM）体系外，依美斯汀的准稳态通量与Ks'呈现良好的线性关系，这表明分配过程在决定渗透速率方面至关重要。乙醇/肉豆蔻酸异丙酯体系的特殊情况可能是由于药物在角质层中的扩散系数增加，这是通过使用双层扩散模型分析得出的。因此，通过吸附和渗透研究对分配和扩散过程进行差异评估，将有助于进一步了解载体对药物皮肤渗透的影响。
