Polymorphism of Pradofloxacin: Crystal Structure Analysis, Stability Study, and Phase Transformation Behavior

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Pradofloxacin, a vital antibiotic, suffers from poor physical stability.
• No prior systematic studies have investigated pradofloxacin's polymorphic forms.

Purpose of the Study:

• To develop novel crystalline forms of pradofloxacin to enhance stability.
• To systematically investigate phase transformation relationships for industrial production guidance.

Main Methods:

• Synthesis of three solvent-free forms (A, B, C), a DMSO solvate (PL-DMSO), and a hydrate (PL-H).
• Single crystal X-ray diffraction for Forms A, B, and PL-DMSO.
• Solid-state analysis (TGA, DSC) and slurry experiments to assess stability and phase transformations.

Main Results:

• Successfully obtained and characterized five new crystal forms of pradofloxacin.
• The new hydrate (Form PL-H) exhibits excellent hygroscopic stability.
• Form B, with enhanced hydrogen bonding and C–H···π interactions, is more stable than Form A.

Conclusions:

• The study provides a comprehensive understanding of pradofloxacin's polymorphic landscape.
• Identified stable crystal forms can guide manufacturing and storage processes.
• The new hydrate shows promise for pharmaceutical development.