Solubility

Purpose

Aqueous solubility is an important determinant of the bioavailability and usefulness of a drug candidate. Nephelometry (light scattering) is an accepted technique to rapidly determine the apparent solubilities of a large number of lead compounds.

Assay Protocol

Test articles are dissolved in DMSO and serially diluted in phosphate buffered saline pH 7.4 (PBS) in a 96 well plate. The diluted compounds have a final concentration range of 2 to 1000 mg/mL and contain ≤1% DMSO. After a 30 minute incubation at room temperature, precipitation is measured by detecting light scattering on a Lab Systems nephelometer. Solubility is determined by comparing the NU (nephelometer units) of four replicates of a sample concentration to the NU of the solvent blank wells. Insolubility is defined as the concentration at which the blank corrected NU is significantly greater than the solvent blank. A 1% difference calculated by Student's T Test is considered to be significant.

Confirmation Data

The solubility assay was performed on eight drug compounds. The results were tabulated and compared to published solubility data based on HPLC measurements of dissolved test article ₍₁₎.

The data shown is an example of representative data obtained from a solubility assay.