Preparation, structural analysis, and properties of tenoxicam cocrystals

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID).
• Cocrystal formation can modify drug properties like solubility and dissolution rate.
• Developing new cocrystals of tenoxicam is crucial for improving its therapeutic efficacy.

Purpose of the Study:

• To screen, prepare, and characterize novel tenoxicam cocrystals.
• To investigate the structural features and molecular interactions within tenoxicam cocrystals.
• To evaluate the impact of cocrystallization on the dissolution rate of tenoxicam.

Main Methods:

• Solvent-drop grinding (SDG) for cocrystal screening and preparation.
• Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and multinuclear solid-state NMR (SSNMR) for structural characterization.
• 1D and 2D SSNMR techniques, including CP-HETCOR and (1)H-(1)H double-quantum interactions, for detailed structural analysis and assessment of ionization states.

Main Results:

• Nine tenoxicam cocrystals were successfully prepared using SDG.
• Structural characterization confirmed the formation of cocrystals with saccharin, salicylic acid, succinic acid, and glycolic acid.
• The tenoxicam-saccharin cocrystal exhibited structural similarity to a known piroxicam-saccharin cocrystal.
• Intrinsic dissolution rates of the four selected cocrystals were comparable to or lower than tenoxicam Form III.

Conclusions:

• Solvent-drop grinding is an effective method for screening tenoxicam cocrystals.
• Solid-state NMR provides valuable insights into cocrystal structure, molecular interactions, and ionization states.
• Cocrystallization of tenoxicam with selected coformers did not significantly enhance its dissolution rate compared to Form III.