Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi's Facilitated Dissolution...

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Analytical Chemistry

Background:

• Accurate equilibrium solubility measurement is crucial for drug development.
• Slowly dissolving compounds require lengthy incubation times, risking sample degradation.
• The Facilitated Dissolution Method (FDM) was proposed to accelerate solubility determination.

Purpose of the Study:

• To systematically validate the Facilitated Dissolution Method (FDM).
• To establish a standardized protocol for FDM application.
• To demonstrate FDM's effectiveness for poorly soluble compounds.

Main Methods:

• Systematic validation of FDM using progesterone as a model compound.
• Comparison of FDM results with the standardized Saturation Shake-Flask (SSF) method.
• Testing FDM under varied conditions (organic solvent type/volume, agitation time, solid excess).

Main Results:

• FDM significantly reduced incubation times for low-solubility compounds to 24 hours.
• The small volume of organic solvent in FDM did not compromise solubility measurements.
• A standardized FDM protocol using 1% v/v organic solvent was proposed and validated.
• Octane, octanol, and 1,2-dichloroethane were identified as suitable organic solvents based on compound lipophilicity.

Conclusions:

• The Facilitated Dissolution Method (FDM) is a valid and efficient technique for determining equilibrium solubility.
• FDM offers a reliable alternative to lengthy incubation periods, especially for poorly soluble compounds.
• The proposed standardized FDM protocol enhances reproducibility and applicability in pharmaceutical research.