Direct Measurement of Amorphous Solubility

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Pharmaceutical Science

Background:

• Amorphous materials possess unique physicochemical properties, notably enhanced solubility compared to crystalline forms.
• Increased solubility of amorphous drugs is vital for improving the bioavailability of poorly water-soluble medications.
• Current analytical methods for direct amorphous solubility assessment are limited.

Purpose of the Study:

• To introduce and validate a novel direct method for measuring amorphous solubility.
• To compare the new method against theoretical estimations and a standard supersaturation/precipitation technique.
• To demonstrate the method's utility for challenging compounds like fast-crystallizing drugs.

Main Methods:

• Development of the single particle analysis (SPA) method, integrating optics and fluidics.
• Comparison of SPA results with theoretical estimations from thermal analysis.
• Comparison of SPA results with a standardized supersaturation and precipitation method.

Main Results:

• The SPA method provides a direct and reliable measurement of amorphous solubility for diverse drugs.
• Good agreement was observed between the SPA method, theoretical estimations, and the supersaturation/precipitation method.
• SPA enabled the first experimental measurement of amorphous solubility for griseofulvin without crystallization inhibitors.

Conclusions:

• The single particle analysis (SPA) approach offers a rapid and straightforward determination of amorphous solubility.
• This method is suitable for small sample amounts (less than 0.1 mg) of amorphous materials.
• The SPA method has broad applicability across materials science, analytical chemistry, and pharmaceutical science.