Aqueous Solubility Assays

Creative Bioarray provides Aqueous Solubility Assays to help customers accurately evaluate the drug solubility, allowing customers to make early modifications to their drugs to alleviate difficulties in the drug research process and improve their bioavailability.

Why is it necessary to determine drug solubility?

• Low solubility can impair the formation of in vitro DMPK or biological data quality, which can be a significant stumbling block in the drug discovery and development process.
• Low solubility may lead to problems in generating suitable formulations for in vivo pharmacokinetic studies.
• Unknown solubility may lead to problems in the absorption of the drug after oral administration. If the drug solubility is known, then the correct and reliable compound concentration will be available.

Brief Protocol

Thermodynamic and kinetic solubility assays are two commonly used laboratory methods to determine drug solubility.

• Kinetic solubility assay (The most common method)

Advantages: Kinetic solubility assay is often used in the early drug discovery process as it is fast and has higher throughput. In this case, the compound does not need to dissolve by overcoming any crystal forces in the solid state because these have been overcome before the experiment by DMSO dissolution.

Materials: Compounds already fully dissolved in an organic solvent.

• After first dissolving the solid compounds in DMSO, each compound's linear series of dilutions is added to an aqueous buffer, and precipitate formation is observed while the compounds are incompletely dissolved.
• After filtration or spin-down to remove the insoluble, solubility can be measured using HPLC-UV or LC-MS/MS.

Figure 2. Two common approaches for kinetic solubility assays (Edward H, 2005).

• Thermodynamic solubility assay

Advantages: Thermodynamic solubility assay is typically a late-discovery screening detection that calculates the equilibrium solubility of a test compound by measuring its concentration in a solution containing excess compound that has been allowed to reach thermodynamic equilibrium. It is useful when preparing a data package for a proposed development candidate.

Materials: Solid crystalline material in aqueous solvent as a saturated solution in equilibrium.

• Add aqueous dissolution to the excess solid compound for a long incubation period to achieve equilibrium dissolution.
• After filtration or spin-down to remove the insoluble, solubility can be measured using HPLC-UV or LC-MS/MS.

Applications

• Solubility data can be used to assess the effect of functional groups on the solubility of compounds and to guide the development of strategies.
• Solubility data can be used to interpret the results of in vitro experiments.
• Solubility can be combined with other in vitro parameters to forecast the oral pharmacokinetics or intestinal absorption of compounds.

Quotation and ordering

If you have any special needs or questions regarding our services, please feel free to contact us. We look forward to cooperating with you in the future.

References

1. Kerns, Edward H., and Li Di. "Automation in pharmaceutical profiling." JALA: Journal of the Association for Laboratory Automation 10.2 (2005): 114-123.
2. Kerns, Edward H., et al. "In vitro solubility assays in drug discovery." Current drug metabolism 9.9 (2008): 879-885.

Explore Other Options

• In Vitro Metabolism
• In Vitro Permeability and Transporters
• Drug-Drug Interaction
• High-throughput ADME Screening
• Physicochemical Characterization Assays

• Chemical Stability Assays
• Lipophilicity and pK_a Assays

For research use only. Not for any other purpose.