Design and in vitro evaluation of novel sustained-release double-layer tablets of lornoxicam: utility of cyclodextrin and xanthan gum combination.
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.
Hamza
Yassin El-Said
Yel-S
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
Aburahma
Mona Hassan
MH
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D015195:Drug Design; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011135:Polysaccharides, Bacterial; D013607:Tablets; D047392:beta-Cyclodextrins; D010894:Piroxicam; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C059451:lornoxicam; C002563:xanthan gum