کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2482791 | 1556296 | 2006 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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 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](/preview/png/2482791.png)
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.
Journal: European Journal of Pharmaceutical Sciences - Volume 28, Issues 1–2, May 2006, Pages 43–50