Atomic pairwise distribution function analysis of the amorphous phase prepared by different manufacturing routes

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Amlodipine besilate, a vital calcium channel antagonist, exhibits polymorphism, with anhydrate and dihydrate forms.
• Solid-state transformations during processing can impact drug efficacy and stability.
• Understanding these changes is crucial for pharmaceutical development.

Purpose of the Study:

• To investigate solid-state changes in amlodipine besilate anhydrate and dihydrate forms.
• To compare the effectiveness of different processing methods (milling, quench cooling) in generating amorphous forms.
• To evaluate analytical techniques for characterizing these solid forms.

Main Methods:

• Processing: Milling of amlodipine besilate anhydrate and quench cooling of the dihydrate form to create amorphous materials.
• Characterization: X-ray powder diffraction (XRPD), Raman spectroscopy, and atomic pair-wise distribution function (PDF) analysis.
• Comparative analysis of analytical technique sensitivity.

Main Results:

• Both milling and quench cooling successfully produced amorphous forms of amlodipine besilate.
• XRPD and Raman spectroscopy provided information on the solid states.
• Atomic pair-wise distribution function (PDF) analysis demonstrated superior sensitivity in differentiating the amorphous samples derived from the two starting materials and processing methods.

Conclusions:

• Solid-state transformations of amlodipine besilate are sensitive to processing conditions.
• Atomic pair-wise distribution function (PDF) analysis is a powerful tool for characterizing subtle differences in amorphous pharmaceutical materials.
• This study highlights the importance of solid-state analysis in drug processing.