ABSTRACT
In the simplest of terms, the solubility of a solute in a given solvent system, as defined by amount of drug dissolved, seems easily determined, but reliable, reproducible and meaningful numbers can be difficult to obtain. The more common methods are best described as “fit for use,” wherein the solid phase of interest is incubated in solvent and the total amount of solute present in solution is measured. The method of solid-phase separation is critical and really defines the utility of the apparent solubility obtained. Typically, either filtration or centrifugation is used with subsequent assay of filtrate (filtration) or supernatant (centrifugation). Details of separation can be particularly important when colloid scale dispersions exist. Furthermore, as solubilities begin to drop below 1 mg/mL, issues of nonspecific adsorption to surfaces (filter, container), coupled with analytical detection limitations can result in highly variable values across labs.
