Quantitative structure-permeation relationships for solute transport across silicone membranes.
OBJECTIVE
The purpose of this work was to assess the molecular properties that influence solute permeation across siliconemembranes and to compare the results with transport across human skin.


METHODS
The permeability coefficients (log Kp) of a series of model solutes across silicone membranes were determined from the analysis of simple transport experiments using a pseudosteady-state mathematical model of the diffusion process. Subsequently, structure permeation relationships were constructed and examined, focusing in particular on the difference between solute octanol/water and 1,2 dichloroethane/water partition coefficients (deltalog P(oct-dce)), which re ported upon H-bond donor activity, and the computationally derived molecular hydrogen-bonding potential.


RESULTS
The hydrogen-bond donor acidity and the lipophilicity of the compounds examined greatly influenced their permeation across sil cone membranes. Furthermore, for a limited dataset, a significant correlation was identified between solute permeation across silicone membranes and that through human epidermis.


CONCLUSIONS
The key molecular properties that control solute perme ation across silicone membranes have been identified. For the set of substituted phenols and other unrelated compounds examined here a similar structure-permeation relationship has been derived for their transport through human epidermis, suggesting application of the results to the prediction of flux across biological barriers.
Geinoz
Sandrine
S
Institut de Chimie Thérapeutique, BEP, Université de Lausanne CH-1015, Lausanne, Switzerland.
Rey
Sebastien
S
Boss
Gilles
G
Bunge
Annette L
AL
Guy
Richard H
RH
Carrupt
Pierre-Alain
PA
Reist
Marianne
M
Testa
Bernard
B
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015194:Diffusion Chambers, Culture / Q000379:methods; D008567:Membranes, Artificial; D008962:Models, Theoretical; D010539:Permeability / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D012828:Silicones / Q000737:chemistry / Q000493:pharmacokinetics*
D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D012828:Silicones