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.