A comparative study of the in vitro permeation of 2-phenoxyethanol in the skin PAMPA model and mammalian skin

For permeation studies that use excised skin, experimental data may show variability associated with the use of biological tissues. As a consequence, achieving reproducible results and data interpretation may be challenging. The skin parallel artificial membrane permeability assay (skin PAMPA) model has been proposed as a high -throughput tool for predicting skin permeation of chemicals. A number of skin cleansing wipe formulations for the diaper area of infants contain 2-phenoxyethanol (PE) as a preservative and cetylpyridinium chloride (CPC) as a surfactant with antimicrobial activity. However, information regarding cutaneous absorption of PE and CPC in the scientific literatures is remarkably limited. The main aim of the present study was to assess the suitability of the skin PAMPA model for prediction of skin permeation of PE. A secondary aim was to investigate the influence of CPC on the dermal absorption of PE. PE (1 % w/w) was prepared in two vehicles, namely propylene glycol (PG) and water-PG (WP). Permeability of PE was investigated in vitro using the skin PAMPA membrane, porcine skin and human skin under finite dose conditions. The highest permeation of PE was observed for the water-PG preparation with 0.2 % w/w of CPC. This finding was consistently observed in the skin PAMPA model and in Franz cell studies using porcine skin and human skin. Permeation of CPC was not detected in the three permeation models. However, permeation of PE increased significantly (p < 0.05) in the presence of CPC compared with formulations without CPC. When comparing the skin PAMPA data and the mammalian skin data for the cumulative amount of PE permeated, the r2 values for PAMPA-porcine skin and PAMPA-human skin were 0.84 and 0.89, respectively. The findings in this study demonstrate the capability of the skin PAMPA model to differentiate between various doses and formulations and are encouraging for further applications of this model as a high throughput screening tool in topical formulation development.

Automated summary

For permeation studies using excised skin, variability in experimental data due to biological tissues can make achieving reproducible results challenging. The skin PAMPA model has been proposed as a high-throughput tool for predicting skin permeation. This study assessed the suitability of the skin PAMPA model for predicting the permeation of 2-phenoxyethanol (PE) and investigated the influence of cetylpyridinium chloride (CPC) on PE dermal absorption.