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

• Main Authors: Anna W. Sobańska (Author), Jeremy Robertson (Author), Elżbieta Brzezińska (Author)
• Format: Book
• Published: MDPI AG, 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Several chromatographic parameters (<b><i>R_M</i>⁰</b> and <b><i>S</i></b> obtained from RP-18 TLC with methanol-pH 7.4 phosphate buffer mobile phases by extrapolation to zero concentration of methanol; <b><i>R_f</i></b> and <b><i>R_M</i></b> obtained from RP-18 TLC with acetonitrile-pH 7.4 phosphate buffer 70:30 <i>v</i>/<i>v</i> as a mobile phase) and calculated molecular descriptors (molecular weight-<b><i>M_W</i></b>; molar volume-<b><i>V_M</i></b>; polar surface area-<b><i>PSA</i></b>; total count of nitrogen and oxygen atoms-(<b><i>N+O</i></b>); H-bond donor count-<b><i>HD</i></b>; H-bond acceptor count-<b><i>HA</i></b>; distribution coefficient-log <b><i>D</i></b>; total energy-<b><i>E_T</i></b>; binding energy-<b><i>E_b</i></b>; hydration energy-<b><i>E_h</i></b>; energy of the highest occupied molecular orbital-<b><i>E_HOMO</i></b>; energy of the lowest unoccupied orbital-<b><i>E_LUMO</i></b>; electronic energy-<b><i>E_e</i></b>; surface area-<b><i>S_a</i></b>; octanol-water partition coefficient-log <b><i>P</i></b>; dipole moment-<b><i>DM</i></b>; refractivity-<b><i>R</i></b>, polarizability-<b><i>α</i></b>) and their combinations (<b><i>R_f</i></b>/<b><i>PSA</i></b>, <b><i>R_M</i></b>/<b><i>M_W</i></b>, <b><i>R_M</i></b>/<b><i>V_M</i></b>) were tested in order to generate useful models of solutes' skin permeability coefficient log <b><i>K_p</i></b>. It was established that neither <b><i>R_M</i>⁰</b> nor <b><i>S</i></b> obtained in the conditions used in this study is a good predictor of the skin permeability coefficient. The chromatographic parameters <b><i>R_f</i></b> and <b><i>R_f/PSA</i></b> were also unsuitable for this purpose. A simple and potentially useful, purely computational model based on (<b><i>N+O</i></b>), log <b><i>D</i></b> and <b><i>HD</i></b> as independent variables and accounting for <i>ca.</i> 83% of total variability was obtained. The evaluation of parameters derived from <b><i>R_M</i></b> (<b><i>R_M</i></b>, <b><i>R_M</i></b>/<b><i>M_W</i></b>, <b><i>R_M</i></b>/<b><i>V_M</i></b>) as independent variables in log <b><i>K_p</i></b> models proved that <b><i>R_M</i></b>/<b><i>V_M</i></b> is the most suitable descriptor belonging to this group. In a search for a reliable log <b><i>K_p</i></b> model based on this descriptor two possibilities were considered: a relatively simple model based on 5 independent variables: (<b><i>N+O</i></b>), log <b><i>D</i></b>, <b><i>R_M</i></b>/<b><i>V_M</i></b>, <b><i>E_T</i></b> and <b><i>E_h</i></b> and a more complex one, involving also <b><i>E_b</i></b>, <b><i>M_W</i></b> and <b><i>PSA</i></b>.

Item Description

10.3390/ph14020147
1424-8247