alexa PAMPA--a drug absorption in vitro model 13. Chemical selectivity due to membrane hydrogen bonding: in combo comparisons of HDM-, DOPC-, and DS-PAMPA models.


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Author(s): Avdeef A, Tsinman O

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Abstract This study compares the intrinsic permeability coefficients of 40 drug molecules, obtained by three popular variants of the PAMPA assay, based on: (a) n-hexadecane, (b) 2\% w/v dioleyoylphosphatidylcholine in n-dodecane, and (c) 20\% w/v lecithin in n-dodecane, the HDM-, DOPC-, DS-PAMPA models, respectively. It was shown that PAMPA permeability values consistently rank in magnitude according to: DS>DOPC>HDM, with molecules like metoprolol showing 1000-fold greater permeability in DS than in HDM. Abraham descriptors were used to rationalize these observations. Water-solubilized polar molecules form very strong H-bonds with the solvent. Such molecules need to break these bonds in order to enter the pure alkane phase, which, in turn, offers no compensating H-bond solvation. Thus, more energy appears to be needed for a polar molecule to penetrate a pure alkane barrier, compared to a barrier possessing some H-bond interactions. The 20\% phospholipid content of the DS-PAMPA lipid may be thought to ease the permeation process, by offering a compensating source of H-bonding within the membrane phase. This article was published in Eur J Pharm Sci and referenced in Autism-Open Access

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