Local tolerance of intraarticular administration of lornoxicam into the rabbit knee joint

Abstract

The local tolerability of lornoxicam (Xefo) after single and repeated intraarticular administration was assessed in the rabbit and compared to established standard therapies (hyaluronic acid--Synvisc and the glucocorticoid triamcinolone--Triam), and the results are discussed in the context of the literature. Two local tolerance studies were performed using five male rabbits per group. Lornoxicam and competitor products were administered into the right knee joint in a volume of 500 μL. The contralateral left knee joint of the same animal was used as the control and was injected with water for injection. Three out of five animals were killed 72 h after the last administration, whereas the remaining two animals were subjected to a 2- or 6-week recovery period in the first and the second study, respectively. Findings revealed adaptive changes related to the mechanical irritation of the injection and to adaptive responses of the synoviocytes, but no signs of toxicity to bone or chondrotoxicity. Toxicokinetic analysis showed a fast and almost complete absorption of lornoxicam from the joints into the systemic circulation. As a conclusion, repeated intraarticular administration of lornoxicam was well tolerated in rabbits.

Dissolution Enhancement and Formulation of Rapid-Release Lornoxicam Mini-Tablets

“…Lornoxicam (LOR) is a non‐steroidal anti‐inflammatory drug (NSAID), with analgesic and anti‐pyretic properties, and although structurally related to piroxicam and tenoxicam, LOR is 10‐fold more potent . Because LOR is used to treat patients with rheumatoid arthritis, osteoarthritis and postoperative management of pain associated with orthopaedic, abdominal and dental surgeries, a rapid onset of action is a desired attribute, but LOR has limited solubility in gastric media which is a rate‐limiting step for rapid absorption .…”

“…Lornoxicam (LOR) is a non-steroidal anti-inflammatory drug (NSAID), with analgesic and anti-pyretic properties, 1 and although structurally related to piroxicam and tenoxicam, LOR is 10-fold more potent. 2 Because LOR is used to treat patients with rheumatoid arthritis, osteoarthritis and postoperative management of pain associated with orthopaedic, abdominal and dental surgeries, 1,3,4 a rapid onset of action is a desired attribute, but LOR has limited solubility in gastric media which is a rate-limiting step for rapid absorption. 5 Several techniques have been investigated to enhance the dissolution of poorly soluble compounds, such as micronisation, 6 formation of inclusion complexes with cyclodextrins, 7-9 micellar solubilisation 10,11 and solid dispersions with hydrophilic macromolecules.…”

Do Nonsteroidal Anti-Inflammatory Drugs Have a Deleterious Effect on Cartilage Repair? A Systematic Review

“…Six studies demonstrated no pathological effects of NSAIDs on chondrocytes. 43,47-52 Ekici et al . 48 used dexketoprofen (COX-1 selective NSAIDs) in a rat model.…”

“…In addition to that, Shroeder et al . 52 reported that repeated administration (1, 2, or 3 times) of lornoxicam into the knee joint was well-tolerated in rabbits. Using hematoxylin and eosin staining, they reported on mechanical irritation and tract inflammation from the injection and adaptive synoviocyte responses; however, no signs of toxicity to bone or chondrotoxicity were found.…”

Chitosan temperature-sensitive gels: reduce the burst release of microspheres containing lornoxicam and enhance drug targeting

“…It is difficult to achieve continuous therapeutic effect after intra-articular injection, because a fast and almost complete absorption of Lornoxicam from the joints into the systemic circulation, so it often needs to be repeated several times. 7 Poly (lactide-co-glycolide acid) (PLGA) microspheres are efficient delivery systems for controlled release of low molecular weight drugs, 8 and its drug release considers both drug dissolution and the diffusion of dissolved active principle through the polymeric matrix. 9 PLGA microspheres have been proved to have good therapeutic effect in the treatment of osteoarthritis.…”