AAPS PharmSciTech

, 20:89 | Cite as

Investigation of the Compatibility of the Skin PAMPA Model with Topical Formulation and Acceptor Media Additives Using Different Assay Setups

  • Melanie KöllmerEmail author
  • Parinaz Mossahebi
  • Elena Sacharow
  • Sascha Gorissen
  • Nicole Gräfe
  • Dirk-Heinrich Evers
  • Michael E. Herbig
Research Article


The Skin Parallel Artificial Membrane Permeability Assay (PAMPA) is a 96-well plate–based skin model with an artificial membrane containing free fatty acid, cholesterol, and synthetic ceramide analogs to mimic the stratum corneum (SC) barrier. The current study evaluates the compatibility of lipophilic solvents/penetration enhancer, topical emulsions containing different emulsifier systems, and organic acceptor media additives with the artificial membrane of the assay. Additionally, different assay setups (standard setup: donor in bottom plate versus modified setup: donor in top plate) were compared. Methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were used as model permeants and internal standards for proper assay execution. The permeation order of the parabens (MP > EP > PP) remained the same with different lipophilic solvents, and the ranking of lipophilic solvents was comparable under standard and modified conditions (isopropyl myristate, IPM > dimethyl isosorbide, DMI ≥ propylene glycol, PG > diisopropyl adipate, DIPA). Pre-incubation of the Skin PAMPA plates with IPM, DIPA, and DMI, as well as with formulations that contain non-ionic emulsifiers, and acceptor solutions containing DMSO or EtOH (≤ 50%) for 4 h did not increase the percentage of permeated parabens in the main experiment, suggesting that those compounds do not make the artificial membrane more permeable. High-resolution mass spectrometry confirmed that acceptor solutions with ≤ 50% DMSO or EtOH do not extract stearic acid, cholesterol, and certramides at standard assay conditions. Hence, if certain constraints are considered, the Skin PAMPA model can be used as a pre-screening tool for topical formulation selection.


skin PAMPA artificial membrane penetration enhancer emulsifier parabens 



Active pharmaceutical ingredient


Diisopropyl adipate


Dimethyl isosorbide


Dimethyl sulfoxide




Isopropyl myristate


Methyl-, ethyl- & propylparaben respectively


Parallel Artificial Membrane Permeability Assay


Propylene glycol


Stratum corneum


Ultra-performance liquid chromatography



The authors thank Elvira Balaguer, Almirall SA, Sant Feliu, Spain, for technical support.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Melanie Köllmer
    • 1
    • 2
    Email author
  • Parinaz Mossahebi
    • 1
  • Elena Sacharow
    • 1
  • Sascha Gorissen
    • 1
    • 2
  • Nicole Gräfe
    • 1
  • Dirk-Heinrich Evers
    • 1
    • 2
  • Michael E. Herbig
    • 1
    • 2
  1. 1.Almirall Hermal, R&D DermatologyReinbekGermany
  2. 2.RaDes GmbHHamburgGermany

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