静止水层对亲水性环糊精增强通透性的影响。

Effect of the unstirred water layer on permeability enhancement by hydrophilic cyclodextrins.

作者信息

Brewster Marcus E, Noppe Marc, Peeters Jef, Loftsson Thorsteinn

机构信息

Chemical and Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium.

出版信息

Int J Pharm. 2007 Sep 5;342(1-2):250-3. doi: 10.1016/j.ijpharm.2007.04.029. Epub 2007 May 6.

DOI:10.1016/j.ijpharm.2007.04.029

PMID:17560057

Abstract

Saturated solutions of three test compounds, carbamazepine, griseofulvin and hydrocortisone, were prepared in aqueous buffer (pH 7.4) containing 0, 1, 5 and 10% HPbetaCD. The permeability and flux of the drugs though a PAMPA membrane at different unstirred water layer (UWL) thicknesses was determined. In absence of HPbetaCD, permeability coefficients increased two- to three-fold with decreasing UWL thickness to a certain minimum values of about 40 microm. Addition of HPbetaCD to systems exhibiting larger UWL thicknesses significantly increased compound flux. The effect of HPbetaCD was linked to its association constant (K(1:1)) with the model drugs and decreased with decreasing UWL thickness to a certain minimum value. This suggests that hydrophilic cyclodextrins enhance flux when the UWL resistance significantly contributes to the overall barrier resistance.

摘要

在含有0%、1%、5%和10% HPβ环糊精的水性缓冲液（pH 7.4）中制备了三种受试化合物（卡马西平、灰黄霉素和氢化可的松）的饱和溶液。测定了不同未搅拌水层（UWL）厚度下药物通过PAMPA膜的渗透率和通量。在不存在HPβ环糊精的情况下，渗透率系数随着UWL厚度减小至约40微米的某个最小值而增加两到三倍。向表现出较大UWL厚度的体系中添加HPβ环糊精显著增加了化合物通量。HPβ环糊精的作用与其与模型药物的缔合常数（K(1:1)）相关，并随着UWL厚度减小至某个最小值而降低。这表明当UWL阻力对整体屏障阻力有显著贡献时，亲水性环糊精会提高通量。