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ADMET and DMPK, Vol. 8 No. 1, 2020.

Original scientific paper

https://doi.org/10.5599/admet.761

Optimization of experimental conditions for skin-PAMPA measurements

Sara Soriano-Meseguer ; Departament de Química Analítica i Institut de Biomedicina, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain
Elisabet Fuguet ; Departament de Química Analítica i Institut de Biomedicina, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain
Adriana Port ; ESTEVE Pharmaceuticals, Drug Discovery and Preclinical Development, Parc Científic de Barcelona, Baldiri Reixac 4-8, 08028 Barcelona, Spain
Martí Rosés ; Departament de Química Analítica i Institut de Biomedicina, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain

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Abstract

In recent years, the parallel artificial membrane permeability assay (PAMPA) has been extended for prediction of skin permeation by developing an artificial membrane which mimics the stratum corneum structure, skin-PAMPA. In the present work, the different parameters affecting skin-PAMPA permeability, such as incubation time and stirring, have been studied to establish ideal assay conditions to generate quality data for a screening of active pharmaceutical ingredients (API) in early stage drug discovery. Another important parameter is membrane retention, which shows dependence on lipophilicity when compounds are in their neutral form. Furthermore, the stability of the membrane has been investigated at different pH values, especially at basic pHs. Finally, a good correlation between human skin permeability and skin-PAMPA permeability, with a large dataset (n = 46), has been established. The optimized assay conditions were an incubation time of 4 hours with stirring in a pH below 8. With all these considerations the thickness of the aqueous boundary layer is decreased as much as possible and the membrane stability is guaranteed.

Keywords

Skin-PAMPA; Permeation; Optimization; Membrane retention; Membrane stability

Hrčak ID:

235011

URI

https://hrcak.srce.hr/235011

Publication date:

4.3.2020.

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