title: Preparation and structural characterization of amorphous spray-dried dispersions of tenoxicam with enhanced dissolution.
abstract: 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 (1) H, (13) C, and (15) N 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.
authors.affiliation: Product Development, GlaxoSmithKline plc., Collegeville, Pennsylvania 19426, USA.
authors.forename: Jagdishwar R
authors.initials: JR
authors.lastname: Patel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Carlton
authors.forename: Fnu
authors.initials: F
authors.lastname: Yuniatine
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Needham
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002853:Chromatography, Liquid; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; C032801:tenoxicam