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.
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.
pION INC, 5 Constitution Way, Woburn, MA 01801-1024, USA. aavdeef@pion-inc.com
Alex
A
Avdeef
Oksana
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Tsinman
D000465:Algorithms; D000473:Alkanes / Q000737:chemistry*; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007408:Intestinal Absorption / Q000502:physiology*; D008567:Membranes, Artificial; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry*; D012044:Regression Analysis; D012995:Solubility
D000473:Alkanes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C017251:1,2-oleoylphosphatidylcholine; C007932:n-hexadecane