Effect of propylene glycol on the skin penetration of drugs


Propylene glycol (PG) has been used in formulations as a co-solvent and/or to enhance drug permeation through the skin from topical preparations. Two skin in vitro permeation approaches are used to determine the effect of PG on drug penetration. The in vitro Skin-PAMPA was performed using 24 actives applied in aqueous buffer or PG. PG modulates permeability by increasing or diminishing it in the compounds with poor or high permeability, respectively. Percutaneous absorption using pigskin on Franz diffusion cells was performed on seven actives and their commercial formulations. The commercial formulations evaluated tend to have a lower permeability than their corresponding PG solutions but maintain the compound distribution in the different strata: stratum corneum, epidermis and dermis. The results indicate the enhancer properties of PG for all compounds, especially for the hydrophilic ones. Additionally, the Synchrotron-Based Fourier Transform Infrared microspectroscopy technique is applied to study the penetration of PG and the molecular changes that the vehicle may promote in the different skin layers. Results showed an increase of the areas under the curve indicating the higher amount of lipids in the deeper layers and altering the lipidic order of the bilayer structure to a more disordered lipid structure.

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The present work could not be performed without the important collaboration and contribution of Isabel Yuste and Service of Dermocosmetic Assessment from IQAC-CSIC. The authors are also grateful to Monserrat Rigol and Núria Solanes from the Department of Cardiology (Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) Hospital Clínic, Universitat de Barcelona, Spain) for supplying the porcine skin biopsies. Moreover, the work carried out in the synchrotron ALBA was possible thanks to the valuable help of M. Kreuzer and I. Yousef and the grant received from the Consortium for the Construction, Equipping and Exploitation of the Synchoton Light Sources (CELLS).


This work was partially funded by the Spanish Ministry of Economy and Competitiveness, project code RTC-2014-1901-1.

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Correspondence to Cristina Alonso.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Animal handling was approved by the Institutional Review Board and Ethics Committee of Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. The management of the Landrace Large White pigs used in this study conforms to the Guide for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (Eighth Edition. Washington, DC: The National Academies Press, 2011).

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Carrer, V., Alonso, C., Pont, M. et al. Effect of propylene glycol on the skin penetration of drugs. Arch Dermatol Res 312, 337–352 (2020). https://doi.org/10.1007/s00403-019-02017-5

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  • Propylene glycol
  • Percutaneous absorption
  • Franz cells
  • µFTIR