Application of RP-18 TLC Retention Data to the Prediction of the Transdermal Absorption of Drugs.

Several chromatographic parameters ( and obtained from RP-18 TLC with methanol-pH 7.4 phosphate buffer mobile phases by extrapolation to zero concentration of methanol; and obtained from RP-18 TLC with acetonitrile-pH 7.4 phosphate buffer 70:30 / as a mobile phase) and calculated molecular descriptors (molecular weight-; molar volume-; polar surface area-; total count of nitrogen and oxygen atoms-(); H-bond donor count-; H-bond acceptor count-; distribution coefficient-log ; total energy-; binding energy-; hydration energy-; energy of the highest occupied molecular orbital-; energy of the lowest unoccupied orbital-; electronic energy-; surface area-; octanol-water partition coefficient-log ; dipole moment-; refractivity-, polarizability-) and their combinations (/, /, /) were tested in order to generate useful models of solutes' skin permeability coefficient log . It was established that neither nor obtained in the conditions used in this study is a good predictor of the skin permeability coefficient. The chromatographic parameters and were also unsuitable for this purpose. A simple and potentially useful, purely computational model based on (), log and as independent variables and accounting for 83% of total variability was obtained. The evaluation of parameters derived from (, /, /) as independent variables in log models proved that / is the most suitable descriptor belonging to this group. In a search for a reliable log model based on this descriptor two possibilities were considered: a relatively simple model based on 5 independent variables: (), log , /, and and a more complex one, involving also , and .