Towards a correlation between drug properties and in vitro transdermal flux variability
Towards a correlation between drug properties and in vitro transdermal flux variability
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DOI：
10.1016/j.ijpharm.2006.11.049
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发表时间：
2007-05-04
影响因子：
5.8
通讯作者：
Meidan, Victor M.
中科院分区：
文献类型：
--
作者：
Frum, Yakov;Khan, Gul M.;Meidan, Victor M.
近年来，越来越多的证据表明，描述任何特定透皮给药系统的渗透系数变异性并不总是正态分布的。然而，由于不同的研究人员使用不同的测试化合物，方法和皮肤类型，很难确定药物性质和通量变化之间的任何一般相关性。本研究的目的是调查这两个变量之间是否存在关系。为此，六种不同的化合物（蔗糖，腺苷，醛固酮，皮质酮，雌二醇和睾酮）表现出一系列的分配系数，但相对相似的分子量进行了筛选，通过采取多个重复测量其渗透曲线，因为它们渗透在猪的皮肤在体外。发现对于相对亲水性溶质（log P-o/w <类似于2.5），促进缓慢透皮通量的物理化学性质与更正偏斜的渗透系数分布相关，而快速通量与更对称的分布相关。然而，没有相关性，可以发现分子特性和统计拟合的程度，无论是正常或对数正态分布之间。(C)2006 Elsevier B. V.保留所有权利。
Over recent years, there has been growing evidence that the permeability coefficient variability describing any specific transdermal drug delivery system is not always normally distributed. However, since different researchers have used different test compounds, methodologies and skin types, it has been difficult to identify any general correlation between drug properties and flux variability. The aim of the present study was to investigate whether there was a relationship between these two variables. To this end, six different compounds (sucrose, adenosine, aldosterone, corticosterone, oestradiol and testosterone) exhibiting a range of partition coefficients but relatively similar molecular weights were screened by taking multiple replicate measurements of their permeation profiles as they penetrated across porcine skin in vitro. It was found that for relatively hydrophilic solutes (log P-o/w < similar to 2.5), physicochemical properties that facilitated slow transdermal flux were associated with more positively skewed permeability coefficient distributions while rapid flux was associated with more symmetric distributions. However, no correlation could be found between molecular properties and the extent of statistical fit to either the normal or log-normal distribution. (C) 2006 Elsevier B.V. All rights reserved.