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Drugs’ skin permeability studies using HPLC chromatographic data obtained on different C18 stationary phases and calculated descriptors
1 , * 1 , 2 , 3 , 1 , 1 , 1
1  Medical University of Lodz, Poland
2  Univesity of Monastir, Tunisia
3  University of Monastir, Tunisia
Academic Editor: Alfredo Berzal-Herranz

Published: 01 November 2023 by MDPI in 9th International Electronic Conference on Medicinal Chemistry session General (registering DOI)

21 randomly selected drugs and excipients of different molecular structures (nipagin M, nipagin P, theophyline, caffeine, triclosan, phenylbutasone, vitamin k3, indomethacin, benzophenone-4, lormetazepam, elenium, naproxen, ibuprofen, bromazepam, aspirin, medazepam, spironolactone, cortisone acetate, olanzapine, chloramfenicol, sumatriptan) were subjected to HPLC chromatography on two different stationary phases: RP-18 and RP-18Ar using the 50:50 (v/v) binary mixture of pH 7.4 phosphate-buffered saline – acetonitrile as a mobile phase. Skin permeability coefficients log Kp of studied compounds were predicted in silico using Pott’s model. The relationships between the chromatographic retention factors log k of compounds listed above obtained for both stationary phases and their predicted skin permeability were investigated. It was concluded that C-18 HPLC retention parameters are not suitable as sole predictors of skin permeability. Multivariate linear (MVL) models of log Kp obtained for the studied group of compounds account for up to 73% of total variability. Calculated and chromatographic descriptors in MVL models were selected in the following order: TPSA (topological polar surface area); #FRB (total count of freely rotatable bonds); log kRP-18Ar (chromatographic retention factor); FCsp3 (fraction of sp3 carbon atoms). Chromatographic retention factors on the RP-18Ar stationary phase are more useful than those obtained on RP-18.

Keywords: Skin permeability; RP-18 HPLC; multivariate linear models; calculated descriptors