Design and in vitro evaluation of novel sustained-release double-layer tablets of lornoxicam: utility of cyclodextrin and xanthan gum combination

AAPS PharmSciTech. 2009;10(4):1357-67. doi: 10.1208/s12249-009-9336-9. Epub 2009 Nov 18.

Abstract

The objective of the present study was to develop new directly compressed, double-layer tablets (DLTs) of lornoxicam, a highly potent nonsteroidal anti-inflammatory drug with short half-life, that are characterized by initial burst drug release in the stomach and comply with the release requirements of sustained-release products. Each of the proposed DLTs is composed of a fast-release layer and a sustained-release layer, anticipating rapid drug release that starts in the stomach to rapidly alleviate the symptoms and continues in the intestine to maintain protracted analgesic effect. An amorphous, freeze-dried inclusion complex of lornoxicam with hydroxypropyl-beta-cyclodextrin, present in 1:2 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of lornoxicam in the stomach and assure rapid onset of its analgesic effect. Xanthan gum (XG), a hydrophilic matrix-forming agent, was integrated in the sustained-release layer to provide appropriate sustainment of drug release. The weight ratios between the sustained-release layer and fast-release layer present in DLTs were adjusted to reach optimal formulations. DLTs composed of sustained-release layer (40% XG) to fast-release layer in 2:1 weight ratio and those composed of sustained-release layer (50% XG) to fast-release layer in 1:1 weight ratio showed the desired release profile. The drug contained in the fast-release layer showed an initial burst drug release of more than 30% of its drug content during the first 30 min of the release study followed by gradual release of the drug for a period of 8 h.

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Calorimetry, Differential Scanning
  • Delayed-Action Preparations
  • Drug Design
  • Piroxicam / administration & dosage
  • Piroxicam / analogs & derivatives*
  • Piroxicam / chemistry
  • Polysaccharides, Bacterial / administration & dosage*
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Tablets
  • X-Ray Diffraction
  • beta-Cyclodextrins / administration & dosage*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Polysaccharides, Bacterial
  • Tablets
  • beta-Cyclodextrins
  • Piroxicam
  • 2-Hydroxypropyl-beta-cyclodextrin
  • lornoxicam
  • xanthan gum