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

Abstract

The new assay allows the simultaneous, small scale screening of drug solubility in various pharmaceutical vehicles and identification of changes in solid form. It is useful for the identification of formulations and formulation options in non-clinical and clinical development.

IUPAC-NIST Solubility Data Series. 102. Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

“…It has also been used in veterinary medicine to treat canines with transitional cell carcinoma of the urinary bladder. 181,182 There have been several publications 64,171,[183][184][185] involving the solubility of piroxicam in organic solvents. Most notably, Bustamante et al 171 measured the mole fraction solubility of piroxicam in 22 different organic solvents, including two saturated hydrocarbons (heptane and cyclohexane), one aromatic hydrocarbon (benzene), one alkyl alkanoate (ethyl ethanoate), one dialkyl ether (1,1′-oxybisethane) and one cyclic ether (1,4-dioxane), two chloroalkanes (trichloromethane and 1,2-dichloroethane) and one chlorinated aromatic hydrocarbon (chlorobenzene), seven alcohols (methanol, ethanol, 1-pentanol, 1-octanol, 1,2-ethanediol, 1,2-propanediol, and 1,2,3-propanetriol), one alkanone (propanone) and one aromatic ketone (acetophenone), and four miscellaneous organic solvents (ethanoic acid, propanoic acid, formamide, and N,Ndimethylformamide) at 298 K and atmospheric pressure.…”

“…Most notably, Bustamante et al 171 measured the mole fraction solubility of piroxicam in 22 different organic solvents, including two saturated hydrocarbons (heptane and cyclohexane), one aromatic hydrocarbon (benzene), one alkyl alkanoate (ethyl ethanoate), one dialkyl ether (1,1′-oxybisethane) and one cyclic ether (1,4-dioxane), two chloroalkanes (trichloromethane and 1,2-dichloroethane) and one chlorinated aromatic hydrocarbon (chlorobenzene), seven alcohols (methanol, ethanol, 1-pentanol, 1-octanol, 1,2-ethanediol, 1,2-propanediol, and 1,2,3-propanetriol), one alkanone (propanone) and one aromatic ketone (acetophenone), and four miscellaneous organic solvents (ethanoic acid, propanoic acid, formamide, and N,Ndimethylformamide) at 298 K and atmospheric pressure. Wyttenbach et al 185 investigated the solubility of piroxicam in ethanol, polyethylene glycol 400, and olive oil at ambient room temperature using a residual solid screening assay method performed in 96-well multiscreen solubility filter plates. Wenkers and Lippold 64 reported solubility data for ten NSAIDs (aspirin, diclofenac, diflunisal, flufenamic acid, ibuprofen, ketoprofen, nabumetone, naproxen, piroxicam, and tenoxicam) in light mineral oil at 305 K. It is not possible to perform a critical evaluation in regard to these solubility data as ethanol is the only common solvent and the independent sets of measurements were performed at different temperatures (298 K and ambient room temperature).…”

In vitro methods to assess drug precipitation

“…In addition to high-throughput feature, some assays allow for the simultaneous, small-scale screening of drug solubilization/precipitation and detection of drug solid or precipitate forms and crystallinity in excipients in a single assay, and therefore, they enables to investigate correlation of drug solubility with solid-state properties of drug precipitate in a high-throughput workflow (Seadeek et al, 2007;Sugano et al, 2006;Wyttenbach et al, 2007). In these assays, a compound and a liquid pharmaceutical vehicle are dispensed into a 96-well filter plate.…”

“…10). The drug solids in the plate are directly analyzed by X-ray powder diffraction (XRPD) (Seadeek et al, 2007;Wyttenbach et al, 2007) or by an automated polarized light microscopy analysis (Sugano et al, 2006). In addition to increasing sample throughput, other approaches focus on use of miniaturization to reduce drug consumption (Chen and Venkatesh, 2004).…”

“…Several studies have demonstrated correlation results between high-throughput/miniaturized assays and bench-scale precipitation assays Chen and Venkatesh, 2004;Dai et al, 2007a,b;Mansky et al, 2007;Wyttenbach et al, 2007). In fact, such high-throughput precipitation assays are often used to rapidly screen out formulations with the highest precipitation potential, then conventional bench-scale precipitation methods are applied to further optimize or refine lead formulation choices for preclinical testing or initial clinical assessment (Chen et al, 2005(Chen et al, , 2003Dai et al, 2007aDai et al, , 2008b.…”