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Title: Optimization of experimental conditions for skin-PAMPA measurements
Author: Soriano-Meseguer, S.
Fuguet i Jordà, Elisabet
Port, Ariadna
Rosés Pascual, Martí
Keywords: Membranes (Tecnologia)
Membranes (Technology)
Issue Date: 4-Mar-2020
Publisher: IAPC Publishing
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.
Note: Reproducció del document publicat a:
It is part of: ADMET & DMPK, 2020, vol. 8, num. 1, p. 16-28
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ISSN: 1848-7718
Appears in Collections:Articles publicats en revistes (Enginyeria Química i Química Analítica)

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