Evaluation of amorphous ursodeoxycholic acid by thermal methods

Area of Science:

• Solid-state chemistry
• Materials science
• Physical chemistry

Background:

• Amorphous forms of drugs can exhibit enhanced solubility and dissolution rates compared to crystalline forms.
• Characterizing the amorphous state is crucial for understanding drug behavior and optimizing formulations.
• Ursodeoxycholic acid (UDCA) is a therapeutic bile acid with potential for amorphous solid dispersions.

Purpose of the Study:

• To characterize different amorphous states of ursodeoxycholic acid (UDCA).
• To investigate the influence of preparation methods on amorphous UDCA properties.
• To demonstrate the utility of thermal analysis for studying amorphous states and dissolution mechanisms.

Main Methods:

• Preparation of amorphous UDCA via grinding and melt cooling.
• Isothermal microcalorimetry to measure heat of solution.
• X-ray diffraction (XRD), infrared (IR) spectroscopy, and solid-state 13C-NMR for structural characterization.
• Differential scanning calorimetry (DSC) for thermal analysis.

Main Results:

• Grinding time affected the heat of solution of UDCA, transitioning from endothermic to exothermic.
• Distinct differences in amorphous UDCA were observed via DSC, IR, and 13C-NMR depending on preparation method.
• Amorphous UDCA stability varied with preparation method under controlled humidity and temperature.
• Heat of solution correlated well with heat of crystallization from DSC.

Conclusions:

• Preparation method dictates the specific state of amorphous UDCA obtained.
• Thermal methods (microcalorimetry, DSC) are effective for evaluating amorphous states.
• The study elucidated the dissolution mechanism of UDCA based on heat of solution data.