The determination of stratum corneum thickness: an alternative approach.

The determination of stratum corneum thickness: an alternative approach.
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DOI:
10.1016/j.ejpb.2008.02.002
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发表时间:
2008-08
期刊:
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子:
--
通讯作者:
L. M. Russell;S. Wiedersberg;M. Delgado-Charro
L. M. Russell;S. Wiedersberg;M. Delgado-Charro
中科院分区:
其他
文献类型:
--
作者:
L. M. Russell;S. Wiedersberg;M. Delgado-Charro

文献摘要

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在皮肤药代动力学研究中,角质层的个体厚度需要使药物渗透曲线正常化。厚度通常用胶带剥离结合经皮失水测量来估计。利用菲克第一定律的线性变换,将逐渐变薄的屏障与相应的经皮失水增加联系起来,并通过线性回归估计其厚度。然而,来自一个重要的主题子集的数据很不适合这个线性模型。这通常是由于去除松散的角质层外层,这对屏障功能没有显著贡献。这项工作提出了两种可选的非线性模型。所有三种模型都用于拟合31个体内胶带剥离实验的数据,并比较它们的结果和拟合优度。结果表明,线性模型可能会高估角质层厚度,并且在拟合数据点的选择上存在主观性。非线性模型令人满意地拟合了所有数据,包括所有数据点。两种非线性模型得出的厚度之间没有显著差异。然而,对模型与数据的拟合优度的分析表明,人们倾向于采用基线校正方法。
The individual thickness of the stratum corneum is required to normalise drug permeation profiles in dermato-pharmacokinetic studies. The thickness is often estimated using tape-stripping combined with transepidermal water loss measurements. A linear transformation of Fick’s first law is used to relate the progressively thinner barrier with the corresponding increase in transepidermal water loss and to estimate the thickness by linear regression. However, the data from an important subset of subjects are poorly fitted to this linear model. This is typically due to the removal of loose outer layers of stratum corneum, which do not contribute significantly to barrier function. This work proposes two alternative non-linear models. All three models were used to fit data from 31 in vivo tape-stripping experiments and their outcomes and goodness-of-fit compared. The results suggest that the linear model may overestimate the stratum corneum thickness and is open to subjectivity regarding the selection of data points to be fitted. The non-linear models satisfactorily fitted all the data, including all data points. No significant differences were found between the thicknesses derived from the two non-linear models. However, the analysis of the goodness-of-fit of the models to the data suggests a preference for a baseline-corrected approach.