Shapes of membrane permeability-lipophilicity curves: extension of theoretical models with an aqueous pore pathway.
Eur J Pharm Sci
; 6(4): 325-29, 1998 Oct.
Article
in En
| MEDLINE
| ID: mdl-9795090
ABSTRACT
The objective of this study was to rationalize the shape of membrane permeability-lipophilicity curves, when considering, in addition to the usual transcellular route, a parallel diffusion pathway through aqueous pores as present in biological membranes. The theoretical influence of different pH in donor and acceptor compartment and the molecular weight on the permeability curves was studied. We combined and extended two previously proposed absorption models, namely one describing diffusion through a simple membrane (two stagnant aqueous and two organic layers in series, no pores) as the sum of the two distribution steps at both membrane interfaces, and a second theoretical model considering the sum of different diffusional resistances through stagnant layers and membrane, respectively. Under certain conditions the equivalence of the two-step distribution model and the diffusional resistance model can be demonstrated. Incorporation of an aqueous diffusion pathway leads to an extended two-step distribution model. This theoretical membrane permeation model will permit a more physicochemical-based interpretation of permeation data and shows that combined log D values and molecular weight are important determinants for membrane transport processes through, e.g. Caco-2 monolayers and the mucosal GI membranes. We have demonstrated that the well-known sigmoidal permeability-lipophilicity relationship should be considered as a molecular weight-dependent set of sigmoidal relationships.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Cell Membrane Permeability
/
Lipids
Language:
En
Journal:
Eur J Pharm Sci
Journal subject:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Year:
1998
Document type:
Article
Affiliation country:
Switzerland
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS