Prediction of blood–brain barrier penetration of poorly soluble drug candidates using surface activity profiling

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 75; no. 3; pp. 405 - 410
• Main Authors: Petereit, Anna Christine, Swinney, Kelly, Mensch, Jurgen, Mackie, Claire, Stokbroekx, Sigrid, Brewster, Marcus, Dressman, Jennifer B.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2010; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier; Cross-sectional area; Drug discovery; General pharmacology; Gibbs adsorption isotherms; Male; Maximum surface pressure; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Solubility; Surface activity profiling; Surface Tension; Gibbs adsorption isotherms; Drug discovery; Maximum surface pressure; Cross-sectional area; Surface activity profiling; Blood–brain barrier; Drug; Pharmaceutical technology; Adsorption isotherm; Prediction; Blood brain barrier; Pressure; Research and development; Penetration; Blood-brain barrier; Pharmacokinetics; Surface activity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.03.015

The aim of this study was to determine whether transepithelial transport across the blood–brain barrier (BBB) [expressed as the logarithm of blood/brain partitioning coefficient (log bb)] could be correlated to surface tension properties for a series of new chemical entities (NCEs) having extremely low solubility in aqueous media. Surface tension data were generated by the “Du Nouy maximum pull force method” using an automated, small volume Kibron Delta 8 Multi-channel tensiometer. Using the surface pressure/concentration profiles, parameters such as the maximum surface pressure, cross-sectional area and the air–water partitioning coefficient were calculated for the individual compounds and correlated with their in vivo log bb values. A good linear correlation ( R 2 = 0.8669) between log bb and cross-sectional area was observed, suggesting a morphological analogy between the molecular orientation at the air–water interface and the anisotropic cellular bilayer of the blood–brain barrier.