A correlation of flux through a silicone membrane with flux through hairless mouse skin and human skin in vitro.
The maximum fluxes of 32 prodrugs and parabens through polydimethylsiloxane membranes from water (EXP log J(MPAQ)) have been correlated with the maximum flux of the same prodrugs and parabens through hairless mouse skin from water (EXP log J(MMAQ)): EXP log J(MMAQ)=0.608 EXP log J(MPAQ)-0.636, r(2)=0.743. The average of the absolute values for the differences between the EXP log J(MMAQ) and the log J(MMAQ) calculated from EXP log J(MPAQ) (Delta log J(MMAQ)) was 0.227 log units. Similarly the maximum fluxes of 11 unrelated permeants through human skin from water (EXP log J(MHAQ)) was correlated with the EXP log J(MPAQ) for the same permeants: EXP log J(MHAQ)=0.516 EXP log J(MPAQ)-0.922, r(2)=0.82 and Delta log J(MHAQ)=0.252 log units. Since the best fit of the databases for EXP log J(MPAQ), log J(MMAQ) and log J(MHAQ) was to the Roberts-Sloan (RS) model, and the dependency of RS on a balance in lipid and aqueous solubility for optimization of topical delivery has been established, the present correlation suggests that the flux through a silicone can be used to predict flux through mouse or human and that the physicochemical properties that lead to optimized flux through one membrane will lead to optimized flux through the others.
Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA.
Scott C
SC
Wasdo
J
J
Juntunen
H
H
Devarajan
K B
KB
Sloan
D000465:Algorithms; D000818:Animals; D016208:Databases, Factual; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D051379:Mice; D008812:Mice, Hairless; D008954:Models, Biological; D009930:Organic Chemicals / Q000737:chemistry* / Q000493:pharmacokinetics*; D010226:Parabens / Q000737:chemistry / Q000493:pharmacokinetics; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility; D014867:Water / Q000737:chemistry
D004129:Dimethylpolysiloxanes; D008567:Membranes, Artificial; D009930:Organic Chemicals; D010226:Parabens; D011355:Prodrugs; D014867:Water; C013830:baysilon