Structural characterization of two polymorphic forms of piroxicam pivalate

Area of Science:

• Crystallography
• Solid-state chemistry
• Pharmaceutical science

Background:

• Piroxicam pivalate is a derivative of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID) from the oxicam class.
• Understanding the solid-state properties of drug molecules, such as polymorphism, is crucial for formulation and efficacy.
• Polymorphs can exhibit different physical and chemical characteristics, impacting drug performance.

Purpose of the Study:

• To elucidate the crystal and molecular structures of two polymorphs of piroxicam pivalate.
• To investigate the unique hydrogen bonding patterns and molecular associations in these polymorphs.
• To correlate structural findings with spectroscopic and diffraction data.

Main Methods:

• Single-crystal X-ray diffraction analysis was employed to determine the detailed crystal structures.
• Infrared (IR) spectroscopy was used to analyze the vibrational properties.
• X-ray powder diffraction (XRPD) patterns were generated computationally and compared with experimental data.

Main Results:

• Two distinct polymorphs of piroxicam pivalate were identified with melting points of 154°C and 136°C.
• The high-melting polymorph forms centrosymmetric dimers through N-H...N hydrogen bonds, an unusual feature for oxicam-class drugs.
• The low-melting polymorph exhibits conformational polymorphism with differing hydrogen bonding arrangements in distinct domains.
• Structural data correlated well with IR spectra, and computed XRPD patterns validated the crystal models.

Conclusions:

• The study reveals novel structural characteristics of piroxicam pivalate polymorphs, including unique dimer formation and conformational polymorphism.
• These findings contribute to the understanding of structure-property relationships in NSAIDs.
• The agreement between experimental and computed diffraction data confirms the accuracy of the determined crystal structures.