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

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. (C) 2010 Elsevier B.V. All rights reserved.