Phase transformation in conformational polymorphs of nimesulide.

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Crystallography

Background:

• Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) and COX-2 inhibitor.
• Two known polymorphs of nimesulide exist: Form I (native) and Form II.
• Understanding nimesulide's polymorphic behavior is crucial for its pharmaceutical development.

Purpose of the Study:

• To conduct a detailed structural characterization of nimesulide polymorphs.
• To investigate the phase stability and transition between nimesulide polymorphs.
• To compare the dissolution properties of different nimesulide crystal forms.

Main Methods:

• X-ray powder diffraction (XRPD) and single-crystal X-ray diffraction for structural analysis.
• Differential scanning calorimetry (DSC) and hot-stage microscopy for phase transition studies.
• Spectroscopic techniques (IR, Raman, ss-NMR) and various crystallization methods (grinding, slurry) for monitoring and inducing phase transitions.

Main Results:

• Two conformational polymorphs, Form I (Pca2(1)) and Form II (C2/c), were crystallized and structurally characterized.
• Nimesulide polymorphs exhibit different torsion angles, stabilized by hydrogen and C-H interactions.
• Phase transition from metastable Form II to stable Form I was confirmed and monitored.
• Metastable Form II demonstrated significantly faster dissolution rates compared to stable Form I.

Conclusions:

• Nimesulide exists as distinct conformational polymorphs with varying structural features.
• The metastable Form II offers enhanced dissolution, potentially influencing bioavailability.
• Knowledge of these polymorphic characteristics is vital for optimizing nimesulide drug product design and performance.