Related Experiment Video
Updated: May 8, 2026

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
Physicochemical characterization and in vitro permeation of an indirubin derivative
Nasim Heshmati1, Bjoern Wagner, Xinlai Cheng
1Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
Abstract:
The active component of the traditional Chinese medicine, indirubin, exerts anticancer effect on different cancer cell lines. E804, a potent derivative of indirubin inhibits the activation of Stat3 and Stat5 in chronic myelocytic leukaemia (CML) cells. However, physicochemical properties and permeation rate of the compound relevant to the drug formulation have never been reported. Therefore, the ionization constant (pK(a)), lipophilicity (logD/P), aqueous and organic solubility of E804 and its permeation across Caco-2 cells were investigated. Both high throughput and traditional determinations were used in this study. The Caco-2 cell permeation assay was carried out in Poloxamer 188/HBSS++ solution in order to maintain the solubility of drug. The potential P-gp (P-glycoprotein) interaction for E804 was determined through Calcein-AM uptake assay. The results showed that E804 did not have a detectable pK(a) in the range of pH 2-11. Log D (distribution coefficient) and Log P (partition coefficient) were determined to be 3.54 ± 0.03. Aqueous solubility test revealed that E804 is practically insoluble in water. Among organic solvents E804 showed the highest solubility in DMSO. The P(app A→B) and P(app B→A) across Caco-2 cell monolayer were 2.0 ± 0.25 × 10(-6)cm/s and 1.14 ± 0.12 × 10(-6)cm/s respectively, and the calculated efflux ratio (ER) was 0.57. Calcein-AM uptake assay showed that E804 was not a strong substrate for P-gp. The results indicate that solubility is the major rate limiting step for the drug permeation. The high membrane permeability makes E804 promising for the oral delivery. Therefore, further investigation on solubility of E804 in lipid vehicles is needed to determine an appropriate formulation for the drug.
Related Concept Videos
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,...
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...
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Drug Product Performance: In Vitro–In Vivo Correlation
Bioavailability Enhancement: Drug Permeability Enhancement
Factors Influencing Drug Absorption: Physicochemical Parameters
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...

