Solubility testing

Solubility is defined as the amount of material that remains in solution in a given volume of solvent containing undissolved material. Solubility of drugs in aqueous media is one of the critical parameters that does influence both pharmacokinetic and pharmacodynamic properties of chemicals. It is a key factor highly influencing dissolution rate and bioavailability of substances following oral administration. Poor solubility is an early indication of compounds that might be difficult and time-consuming to develop due to problems in formulation, process development and safety. For that reason determining aqueous solubility is crucial  in the discovery-development process and can help improve the properties responsible for in vivo performance.

Method: A filter-based method of determining compound solubility in water is carried out in a 96 well format using the MultiScreen Solubility filter plate. This 96-well system is used to classify or quantify the aqueous solubility of compound libraries stored in solvent as a concentrated solution. Compounds solubilized in water-miscible solvents are added to buffer in a filter plate and incubated on a shaker deck. The filter plate is then transferred to a vacuum manifold and samples are filtered. A fixed volume of each filtrate is transferred to a UV-transparent analysis plate to determine the concentration of soluble component by UV spectroscopy. Solubility concentration can also be determined by LC/MS/MS or HPLC detection methods convenient for compounds with low purity (<90%) or low extinction coefficients. Depending on the type of analysis - semi-quantitative or quantitative - a single calibrator or standard solutions are transferred to the plate and absorbance is measured.