A novel design of artificial membrane for improving the PAMPA model.
OBJECTIVE
Since the first demonstration of PAMPA, the artificial membrane has been traditionally prepared by impregnating a porous filter with a solution of lipid mixture. While the lipid solution-based method is simple and seems to provide good predictability for many compounds, it is challenged by several shortcomings including reproducibility, stability, mass retention and the incorrect prediction of a group of highly permeable compounds including caffeine and antipyrine. Here we present the validation of a novel artificial membrane formed by constructing a lipid/oil/lipid tri-layer in the porous filter.


METHODS
Permeability values obtained from traditional and new artificial membrane were compared for their correlation with Caco-2 and human absorption values. Mass retention, stability and organic solvent compatibility of the new artificial membrane were studied.


RESULTS
The new artificial membrane correctly predicts the permeability of the traditionally under-predicted compounds and improves the correlation with Caco-2 and human absorption values. Furthermore, the new artificial membrane reduces the mass retention of compounds that are highly retained by the traditional artificial membrane. The new artificial membrane is also found to be robust enough to sustain long term storage and has good compatibility with organic solvents.


CONCLUSIONS
The new artificial membrane provides an improved PAMPA model.
Chen
Xiaoxi
X
BD Biosciences Discovery Labware, 2 Oak Park, Bedford, Massachusetts 01730, USA. Kevin_chen@bd.com
Murawski
Anthony
A
Patel
Karishma
K
Crespi
Charles L
CL
Balimane
Praveen V
PV
D000042:Absorption; D000465:Algorithms; D002021:Buffers; D018938:Caco-2 Cells; D015195:Drug Design; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008956:Models, Chemical; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012997:Solvents
D002021:Buffers; D008055:Lipids; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D012997:Solvents