Frum Yakov, Khan Gul M, Sefcik Jan, Rouse Jennifer, Eccleston Gillian M, Meidan Victor M
Division of Pharmaceutical Sciences, University of Strathclyde, SIPBS, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK.
Int J Pharm. 2007 May 4;336(1):140-7. doi: 10.1016/j.ijpharm.2006.11.049. Epub 2006 Nov 28.
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)< or = approximately 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.
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呈正态分布。然而，由于不同的研究人员使用了不同的测试化合物、方法和皮肤类型，因此很难确定药物性质与通量变异性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，通过对六种不同化合物（蔗糖、腺苷、醛固酮、皮质酮、雌二醇和睾酮）在体外透过猪皮肤时的渗透曲线进行多次重复测量，筛选出了一系列分配系数但分子量相对相似的化合物。结果发现，对于相对亲水性溶质（log P(o/w)≤约2.5），促进缓慢透皮通量的物理化学性质与更正偏态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，在分子性质与对正态或对数正态分布的统计拟合程度之间未发现相关性。
