Stratified Quantitative Analysis of the Penetration of Active Ingredients in the Skin by Infrared Spectroscopic Imaging

Abstract

A stratified quantitative analysis method for active ingredients in the skin was developed by integrating microscopic infrared spectroscopy, chemometrics, and machine learning. Hierarchical clustering of the stratum corneum, active epidermis, and dermis of control skin slice was performed by spectral clustering algorithm, followed by classification of the skin with active ingredients by Fisher's linear discriminant analysis. The classification results matched well with the bright-field images obtained from the microscope. Based on the corresponding division of the hierarchical structure of the skin, the relative permeation concentrations of the active ingredients in each layer of the skin were calculated using non-negative least squares. Then, a correction factor was introduced by applying the same calculation process to formulations with known concentrations of active ingredients, converting the relative concentrations to the actual concentrations of the active ingredients in each layer of the skin. To demonstrate the effectiveness of this analytical method, hydroxypropyl tetrahydropyrantriol and a polypeptide were selected as active ingredients, and their penetration profiles in the skin were analyzed and visualized.

Keywords: transdermal penetration, stratification quantitative analysis, focal plane array, visualization image