Modeling of flux through silicone membranes from water.
Do the Roberts-Sloan (RS) or modified Kasting-Smith-Cooper (KSC) equations that provide good fit to data for maximum flux, from water through mouse or human skin also provide a good fit to data for maximum fluxes through silicone membranes (polydimethylsiloxane, PDMS). The maximum fluxes through silicone membranes from water (J(MPAQ)), molecular weights (MW), solubilities in isopropyl myristate (S(IPM)) and water (S(AQ)) of 31 prodrugs and one parent drug have been fitted to the RS equation, which includes a parameter for dependence on S(AQ), and the KSC equation, which does not, to determine which equation gave the better fit. In addition, the J(MPAQ), MW, S(AQ) and solubilities in octanol (S(OCT)) of 26 diverse molecules from other laboratories were collected and fitted to the RS and KSC equations to determine if the choice of lipid parameter (S(IPM) or S(OCT)) had an effect on which equation gave the better fit. RS gave the better fit to the present prodrug database where: logJ(MPAQ)=-2.454+0.716 logS(IPM)+0.284 logS(AQ)+0.00208 MW, r(2)=0.77. RS also gave the better fit to the database from other laboratories where: logJ(MPAQ)=-2.046+0.667 logS(OCT)+0.333 logS(AQ)-0.00374 MW, r(2)=0.878 after four obvious outliers were removed to give n=22. Thus, data for J(MPAQ) can be fitted to the RS equation, which also provides the best fit to maximum flux from water through mouse or human skin and includes a dependence on S(AQ).
Wasdo
Scott
S
Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA.
Juntunen
Juha
J
Devarajan
Hema
H
Murray
Thomas
T
Nickels
Donna
D
Singh
Surjit
S
Shanks
Thea
T
Ulmer
Karen
K
Sloan
Kenneth B
KB
D019840:2-Propanol / Q000737:chemistry; D000818:Animals; D004058:Diffusion; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008956:Models, Chemical; D015394:Molecular Structure; D008970:Molecular Weight; D000442:Octanols / Q000737:chemistry; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D004129:Dimethylpolysiloxanes; D008055:Lipids; D008567:Membranes, Artificial; D000442:Octanols; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; C013830:baysilon; D019840:2-Propanol