Optimization of experimental conditions for skin-PAMPA measurements

Abstract

<jats:p>&lt;p class="ADMETabstracttext"&gt;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.&lt;/p&gt;</jats:p>

Commercially Available Cell-Free Permeability Tests for Industrial Drug Development: Increased Sustainability through Reduction of In Vivo Studies

“…As depicted in Figure 9 , the rate-limiting step in the permeation through the PAMPA barrier is the partition/distribution of the drug molecules from the water into the lipoidal environment that fills the filter pores. This supports a reasonable correlation between PAMPA permeabilities and logP [ 61 ]. However, this barrier structure does not allow for small hydrophilic compounds to take advantage of their chemical spaces, e.g., their small size and hydrophilic nature, as would occur in cell lines or in vivo, where small hydrophilic compounds can cross the biological barriers through the paracellular pathway [ 62 ].…”

In Silico Prediction of Skin Permeability Using a Two-QSAR Approach

“…To imitate their applications in the real world, the derived HSVR and PLS models were applied to those compounds assayed by Soriano-Meseguer et al [ 102 ], of which, 23 were also included in this investigation, providing a good way to calibrate the challenge system. Nevertheless, Soriano-Meseguer et al measured the effective permeability coefficient ( P e ) based on the skin-PAMPA system.…”

Evaluation of the Ability of PAMPA Membranes to Emulate Biological Processes through the Abraham Solvation Parameter Model

“…To prepare them, 25 mL of concentrated PRISMA HTTM was diluted to 1 L with water, and 0.5 M NaOH was added to obtain the desired pH. Above pH 8, the skin-PAMPA membrane becomes degraded [ 40 ], so pH 7.4 was the highest pH used in the present work. In order to measure the intrinsic permeability, each sample was dissolved in the buffer solution with a pH that ensured the presence of the neutral form.…”

“…According to previous studies, in which the conditions in the skin-PAMPA measurements were optimized [ 40 ], the skin-PAMPA sandwich was incubated at 32 °C for 4 h. Afterwards, the concentration of the compounds was measured in both the donor and the acceptor plates. Additionally, the initial sample solution was quantified.…”