Shake falsk method is used to determine thermodynamic solubility. It is the thermodynamic constant of the equilibrium between a compound in solid form and the buffer in which it dissolves.
Thermodynamic evaluation assesses the solubility of a solid crystalline material in an aqueous solvent as a saturated solution at equilibrium.

The importance of thermodynamic evaluation is greatest in late discovery and early development, where it is used to confirm previous kinetic solubility results, eliminate potential artifacts, and generate high-quality solubility data using a crystalline material.

Poorly water-soluble compounds are difficult to handle and detect. Precipitate formation can lead to erroneous conclusions about biological functions, and serial dilutions can lead to errors in concentrations.


MatrixPBS pH 7.4
Test temperatureRoom temperature
Incubation time24h
ControlsFlunarizine and haloperidol
Analysis methodHPLC-UV
Data deliverySolubility in µM and mg/mL


For ionisable compounds, solubility depends strongly on pH

Hydrophobic compounds are poorly absorbed because molecules cannot reach gastric epithelium. A high solubility doesn’t mean necessarily a good intestinal absorption.