Preparation, structural analysis, and properties of tenoxicam cocrystals

• Published in: International journal of pharmaceutics Vol. 436; no. 1-2; pp. 685 - 706
• Main Authors: Patel, Jagdishwar R., Carlton, Robert A., Needham, Thomas E., Chichester, Clinton O., Vogt, Frederick G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2012
• Subjects: anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Calorimetry, Differential Scanning; Carboxylic Acids - chemistry; Cocrystal; Crystallization; Differential scanning calorimetry; Dissolution rate; Drug Compounding; glycolic acid; grinding; hydrogen bonding; ionization; Magnetic Resonance Spectroscopy; Molecular Structure; nuclear magnetic resonance spectroscopy; Physical characterization; Piroxicam - analogs & derivatives; Piroxicam - chemistry; Polymorphism; Powder Diffraction; saccharin; Saccharin - chemistry; salicylic acid; screening; Solid-state NMR; Spectroscopy, Fourier Transform Infrared; succinic acid; thermal analysis; X-Ray Diffraction; Solid-state NMR; Differential scanning calorimetry; Dissolution rate; Cocrystal; X-ray diffraction; Physical characterization; Polymorphism
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2012.07.034

Cocrystals of tenoxicam, a non-steroidal anti-inflammatory drug, are screened, prepared, and characterized in this study. Nine tenoxicam cocrystals were identified using solvent-drop grinding (SDG) techniques. Structural characterization was performed using powder X-ray diffraction (PXRD), differential scanning calorimetry, and multinuclear solid-state NMR (SSNMR). Thermal analysis, PXRD, and 1D SSNMR are used to detect solvates and phase mixtures encountered in SDG cocrystal screening. 2D SSNMR methods are then used to confirm cocrystal formation and determine structural aspects for selected cocrystals formed with saccharin, salicylic acid, succinic acid, and glycolic acid in comparison to Forms I and III of tenoxicam. Molecular association is demonstrated using cross-polarization heteronuclear dipolar correlation (CP-HETCOR) methods involving 1H and 13C nuclei. Short-range 1H–13C CP-HETCOR and 1H–1H double-quantum interactions between atoms of interest, including those engaged in hydrogen bonding, are used to reveal local aspects of the cocrystal structure. 15N SSNMR is used to assess ionization state and the potential for zwitterionization in the selected cocrystals. The tenoxicam saccharin cocrystal was found to be similar in structure to a previously-reported cocrystal of piroxicam and saccharin. The four selected cocrystals yielded intrinsic dissolution rates that were similar or reduced relative to tenoxicam Form III.