Abstract
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: log
J
MPAQ
=
−2.454
+
0.716
log
S
IPM
+
0.284
log
S
AQ
+
0.00208
MW,
r
2
=
0.77. RS also gave the better fit to the database from other laboratories where: log
J
MPAQ
=
−2.046
+
0.667
log
S
OCT
+
0.333
log
S
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.