Development of a partially automated solubility screening (PASS) assay for early drug development

Miniaturized Assay for Solubility and Residual Solid Screening (SORESOS) in Early Drug Development

“…Drug slurry is filled into the tubing, continuously circulated inside through a syringe filter and finally drug in the collected filtrate is analyzed by HighPressure Liquid Chromatography (HPLC). Recently, a new partially automated solubility screening (PASS) assay for early drug development was published by Alsenz et al (7). In this assay, the solubility of drug compounds in aqueous and non-aqueous solvents is determined in a 96-well system up to 100 mg/ml drug concentration at a 40 to 80 ml scale.…”

“…SolidY liquid separation is performed by filtration and drug concentration in the filtrate is determined by Ultra Performance Liquid Chromatographyi (UPLC) (8,9). A head-to-head comparison of several solubility assays is discussed by Alsenz et al (7).…”

“…In HT solubility screening, the residual solids are rarely investigated systematically, although transitions to different solid forms in the presence of liquid pharmaceutical excipients or vehicles have been reported (7,10,11). Many drugs form polymorphs and solvates that can have different physicochemical properties such as melting point, enthalpy of fusion, vapor pressure, density, hardness, color, dissolution rate and that can differ considerably in solubility (12,13).…”

Physicochemical Profiling in Drug Research and Development

“…During a 24 h incubation period the plate is agitated by a shaking mechanism, then filtrated and the concentration is measured using a UV plate reader [93]. Another promising HT procedure is the PASS (Partially Automated Solubility Screening) method, where the compounds are suspended in heptane and dispensed into the plate wells, then heptane is evaporated before buffer is added [94].…”

Suggested Improvements for Measurement of Equilibrium Solubility-pH of Ionizable Drugs

“…Partially-Automated Solubility Screening (DMSO-free 'PASS' Method) Alsenz et al [76] described the microtitre plate Partially-Automated Solubility Screening (PASS), where solid compounds (DMSO-free) are suspended as slurries in volatile heptane, sonicated to increase fractionation and dispersion, and then dispensed quickly in small aliquots into microtitre plate wells. From the dispensed volume, the weight of drug is calculated.…”