Related Experiment Video
Updated: Oct 5, 2026

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
Synthesis, in vitro skin permeation studies, and PLS-analysis of new naproxen derivatives
H Weber1, U Steimer, R Mannhold
1Department of Pharmaceutical Chemistry, Heinrich-Heine-Universität Düsseldorf, Germany. Horst.Weber@uniduesseldorf.de
Purpose:
To synthesize new naproxen (01) derivatives with amide or ester structures or with a combination of the two (02-15). To compare their physicochemical properties with naproxen esters (16-22) and their respective skin permeation behavior. To study structure-permeation relationships via partial least squares (PLS)-analysis.
Methods:
Stability, aqueous, and octanol solubility were determined. Lipophilicity and further 53 chemical descriptors were computed. A suitable in-vitro skin permeation model was developed to compare maximal flux (Jmax) of derivatives. Based on these flux data, PLS-analysis was performed to derive structure-permeation relationships.
Results:
None of the new derivatives showed an improved flux in comparison to naproxen. This result can be explained by PLS-analysis: skin permeation increases with the solubility both in water and in octanol. For a good permeation, an optimized molecule should exhibit a small volume with a spherical shape. The surface area should be large in relation to volume, as indicated by the rugosity parameter. A clear separation between the hydrophobic and the hydrophilic domain (= high amphiphilic moment) is favorable. Lipophilicity is inversely correlated with skin permeation.
Conclusions:
PLS-analysis is a valuable tool to derive significant, internally predictive quantitative models for structure-permeation relationships of naproxen derivatives in the above described skin permeation assay.
Related Concept Videos
Methods for Studying Drug Absorption: In vitro
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
In Vitro Drug Dissolution: Alternative Methods
Methods for Studying Drug Absorption: In situ
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
Bioavailability Enhancement: Drug Permeability Enhancement
Drug Product Performance: In Vitro–In Vivo Correlation
In Vitro Drug Dissolution: Compendial Testing Models I
