Preparation and Structural Characterization of Amorphous Spray-Dried Dispersions of Tenoxicam with Enhanced Dissolution

• Published in: Journal of pharmaceutical sciences 2012-02, Vol.101 (2), p.641-663
• Main Authors: Patel, Jagdishwar R., Carlton, Robert A., Yuniatine, Fnu, Needham, Thomas E., Wu, Lianming, Vogt, Frederick G.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Biological and medical sciences; Chromatography, Liquid; dissolution; General pharmacology; infrared spectroscopy; Magnetic Resonance Spectroscopy; mass spectrometry; Medical sciences; microscopy; Microscopy, Electron, Scanning; Molecular Structure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Piroxicam - analogs & derivatives; Piroxicam - chemistry; Powder Diffraction; solid dispersion; solid-state NMR; solid-state stability; Solubility; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; supersaturation; thermal analysis; X-ray diffractometry
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22800

Tenoxicam is a poorly soluble nonsteroidal anti-inflammatory drug. In this work, the solubility of tenoxicam is enhanced using amorphous spray-dried dispersions (SDDs) prepared using two molar equivalents of l-arginine and optionally with 10%–50% (w/w) polyvinylpyrrolidone (PVP). When added to the dispersions, PVP is shown to improve physical properties and also assists in maintaining supersaturation in solution. The dispersions provide a twofold increase over equilibrium solubility at the same pH. The dispersions are characterized using electron microscopy, vibrational spectroscopy, diffuse-reflectance visible spectroscopy, and X-ray powder diffraction. The structures of the dispersions are probed using solid-state nuclear magnetic resonance (SSNMR) experiments applied to the 1H, 13C, and 15N nuclei, including two-dimensional dipolar correlation experiments that detect molecular association and the formation of a glass solution between tenoxicam, l-arginine, and PVP. Other aspects of the amorphous structure, including hydrogen-bonding interactions and the ionization state of tenoxicam and l-arginine, are also explored using SSNMR methods. These methods are used to show that the SDDs contain an amorphous l-arginine salt of tenoxicam in a glass solution that also includes PVP when present. Finally, the dispersions show only a minor decrease in chemical stability during accelerated stability studies relative to a crystalline form of tenoxicam. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.