(T1030-03-14) Investigation of Phenoxyethanol Permeation Using the Skin Parallel Artificial Membrane Permeability Assay (PAMPA) Membrane and Mammalian Skin: Correlation and Rank Order

Tuesday, October 18, 2022

10:30 AM – 11:30 AM ET

Presenting Author(s)

Annisa Rahma, MSc (she/her/hers)

PhD candidate
University College London
LONDON, England, United Kingdom

Main Author(s)

Annisa Rahma, MSc (she/her/hers)

PhD candidate
University College London
LONDON, England, United Kingdom

Purpose: Phenoxyethanol (PE) is the most commonly used preservative ingredient in baby wipe formulations, typically at 0.5-1% v/v. Some baby wipe formulations also contain cetylpyridinium chloride (CPC), a quaternary surfactant with antimicrobial activity. To date there is no information in the published scientific literature regarding skin permeation of PE in the presence of surfactant(s). Ideally, the in vitro permeation of chemicals is assessed in biological tissue. However, high variability between donors may be challenging when interpreting experimental data. The skin Parallel Artificial Membrane Permeability Assay (PAMPA) model has been proposed as a high throughput tool for in vitro skin permeation [1]. The main aim of the present study was to assess the suitability of the skin PAMPA model for prediction of skin permeation of PE from different formulations. Therefore, in vitro studies were conducted to compare permeation of PE in the skin PAMPA model and in porcine skin or human skin. A secondary aim was to investigate the rank order for permeation of PE from various formulations in these models.

Methods: Permeation of PE was determined in vitro using the skin PAMPA model and Franz diffusion cells with excised porcine skin or human skin. The formulations used in this study are listed in Table 1. Permeation studies were conducted for 1 h in the PAMPA model with applied doses ranging from 3-10 µl/cm². For Franz diffusion studies, the assay was conducted for 24 h with an applied dose of 10 µl/cm².

Results: A good correlation between the applied dose and the cumulative amount of PE permeated in the skin PAMPA model was observed. This was indicated by the Pearson’s correlation coefficient (r²) of 0.99. The highest permeation of PE was observed for WP2, the formulation that most closely resembles actual baby wipe formulations. This finding was consistently observed in the skin PAMPA model and in Franz cell studies using porcine skin and human skin. The cumulative amounts of PE that permeated from WP2 in the skin PAMPA model were 85 µg/cm², accounting for 88% of the applied dose. For the porcine skin and human skin studies, the cumulative amounts of PE permeated from this formulation was 96.98 µg/cm² and 92.46 µg/cm², respectively. These values corresponded to more than 97% of the applied dose. In contrast, permeation of CPC was not detected in the three models. Mass balance studies using porcine skin and human skin confirmed that more than 90% of CPC from the applied dose was recovered from the skin surface. Interestingly, while permeation of CPC was not detected in both models, it enhanced the permeation of PE significantly (p < 0.05) compared to formulations without CPC. The rank order for PE permeation from various formulations in the skin PAMPA model was WP2 >PG3 >WP3 >PG2 >WP1 >PG1. For the Franz cell studies, the rank order for PE permeation was WP2 >PG3 >PG2 >WP3 >WP1 >PG1. This trend was consistent both in the porcine skin assay and human skin assay. When comparing the skin PAMPA data and the porcine skin data for cumulative amount of PE permeated, the r² value was 0.84. This value is consistent with previously reported data by Zhang et al. [2]. A greater correlation was observed between the skin PAMPA and human skin data for cumulative amount of PE permeated, with r² value of 0.89.

Conclusion: This work confirms the potential of the PAMPA as a predictive tool for skin permeation. This was demonstrated by the correlation between the applied dose and cumulative amount of PE permeated in the skin PAMPA model – r² of 0.99. Secondly, a positive correlation between the skin PAMPA model and the Franz cell studies using porcine skin and human skin was observed for the cumulative amount of PE permeated (r² of ≥0.84). Future studies will investigate in vivo permeation of PE in human skin and the in vitro-in vivo correlation (IVIVC) between the skin PAMPA model and human skin in vivo for the permeation of PE.

References: 1. Sinkó B, Garrigues TM, Balogh GT, Nagy ZK, Tsinman O, Avdeef A, et al. Skin-PAMPA: A new method for fast prediction of skin penetration. Eur J Pharm Sci. 2012;45(5):698-707.
2. Zhang Y, Lane ME, Hadgraft J, Heinrich M, Chen T, Lian G, et al. A comparison of the in vitro permeation of niacinamide in mammalian skin and in the Parallel Artificial Membrane Permeation Assay (PAMPA) model. Int J Pharm. 2019;556:142-9.

Acknowledgments: We thank our colleagues from the UCL Skin Research Group who provided insight and expertise that greatly assisted the research.

Funding: A.R. is grateful for studentship funding from the Ministry of Finance of The Republic Indonesia (Grant Ref: S-1778/LPDP.4/2019).
Conflict of interest: The authors declare no conflict of interest.

Table 1. PE Formulations used in permeation studies

Figure 1. Permeation of PE from various formulations in the skin PAMPA model, porcine skin, and human skin.