Linear Free Energy Relationship Analysis of Retention Factors in Cerasome Electrokinetic Chromatography Intended for Predicting Drug Skin Permeation

Linear combination methods for prediction and interpretation of drug skin permeation

“…In detail, these are the excess molar refraction (E), the solute dipolarity/polarizability (S), the overall solute hydrogen bond acidity (A) and hydrogen bond basicity (B), the McGowan characteristic volume (V), a descriptor for cations (J + ), and another for anions (J - Eq. (3) is able to describe both the retention factors in LEKC and the distribution coefficient at pH 7.4 (D 7.4 ) between water and different solvents for all tested compounds including non-ionic and ionic substances [11].…”

“…For this reason, many in-vitro models, mimicking the composition and the structure of human stratum corneum, have been investigated so far in order to mathematically describe the process of skin permeation [7][8][9][10][11]. Likewise, different methods have been studied to analyse the raw data obtained in such experimental setups.…”

“…The lower case letters (e, s, a, b, v, j + , j -) are system constants describing the contribution of the solvent phase to the sorption process [11]. The capital letters are solute descriptors representing the properties of the compounds.…”

“…Most studies applying LEKC for studying skin penetration have used conventional phosphatidylcholine (PC)/phosphatidylserine (PS) liposomes which do not reflect the composition of the lipid layers in the stratum corneum. Zhang et al performed LEKC measurements using Cerasome 9005, a 6.6 % (w/w) vesicular dispersion composed of hydrogenated lecithin, ceramides (NP and NS), cholesterol and fatty acids (palmitic acid and oleic acid) [11]. The mixture resembles the composition of the stratum corneum lipids which consist of 40-50 % ceramides, about 25 % sterols, mainly cholesterol, and 10-20 % free fatty acids.…”

“…All following considerations regarding the interpretation of LEKC retention factors are based on a comprehensive dataset created by Zhang, K. et al [11], which comprises experimentally determined log k 7 not be found, HSPs were calculated using the group contribution method of Hoftyzer and van Krevelen [40]. Octanol-water distribution coefficients (log D 7.4 ) were compiled from six sources.…”