High throughput solubility measurement with automated polarized light microscopy analysis.
As a high throughput solubility assay, the solution-precipitation method using a dimethylsulfoxide (DMSO) sample stock solution (DMSO-SP) has been widely used in drug discovery. However, the solid form of the precipitant has not been investigated. In this study, we investigated the experimental conditions of the DMSO-SP, focusing on the solid form of the precipitant. The final concentration of DMSO was 1% (v/v). The precipitant of more than a half of the model compounds was observed as crystalline by polarized light microscopy analysis. When the incubation time was 20 h and the precipitant was crystalline, the DMSO-SP solubility was similar to the solubility from a powder material (PWD). However, when the incubation time was 10 min and/or the precipitant was not crystalline, the DMSO-SP solubility was higher than the PWD solubility. These results suggested that the information regarding the solid form of the precipitant is important in interpreting the solubility data. In addition, we developed an automated birefringence diagnose system for drug discovery usage.
Sugano
Kiyohiko
K
Global Research & Development, Nagoya Laboratories, Pharmaceutical R&D, Pfizer Inc., 5-2 Taketoyo, Aichi 470-2393, Japan. Kiyohiko.Sugano@pfizer.com
Kato
Teruhisa
T
Suzuki
Kentaro
K
Keiko
Kako
K
Sujaku
Tetsujo
T
Mano
Takashi
T
D020003:1-Octanol / Q000737:chemistry; D011232:Chemical Precipitation; D003460:Crystallization; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D015195:Drug Design; D008859:Microscopy, Polarization; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
D004364:Pharmaceutical Preparations; D014867:Water; D020003:1-Octanol; D004121:Dimethyl Sulfoxide