Optimizing solubility: kinetic versus thermodynamic solubility temptations and risks.

The aim of this study was to assess the usefulness of kinetic and thermodynamic solubility data in guiding medicinal chemistry during lead optimization. The solubility of 465 research compounds was measured using a kinetic and a thermodynamic solubility assay. In the thermodynamic assay, polarized-light microscopy was used to investigate whether the result referred to the crystalline or to the amorphous compound.

Characterization of a new solvate of risedronate.

Three new forms of the osteoporosis drug sodium risedronate, sodium [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonate, were identified and designated as the J, K, and M phases. Form J is an acetic acid disolvate with the chemical composition Na(+) [C(7) H(10) NO(7) P(2)](-) · 2CH(3) COOH, as determined by single-crystal structure analysis. This novel solvate is easily formed by the recrystallization of sodium risedronate from acetic acid.

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 (logbb)] 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 logbb values.