Rapid Solubility Determination Using Vapor-Phase Osmometry

Abstract

Because of the need for resource-sparing assays of the solubility of new drug candidates, we sought to develop and validate a rapid method for determining the solubility of nonvolatile pharmaceutical solids in water. Vapor-phase osmometry was used to determine the concentration of drugs in saturated solutions prepared by a rapid ultrasound-mediated dissolution protocol. The osmolality of saturated solutions as measured by the vapor-phase osmometer is an excellent predictor of the solubility of pharmaceutical solids in water. Each osmolality measurement requires less than 10 ul of saturated solution and takes less than 2 min to complete. For small-molecule drugs with solubilities greater than 10 g/kg, osmometry may prove to be a rapid and accurate method for determining the water solubilities of drugs.