Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation.

BACKGROUND AND AIM: Rheumatoid arthritis treatment aims to control joint damage and any associated complications such as cardiovascular disease. Most anti-inflammatory drugs have a high tendency to cause gastro-intestinal irritation. The present study is designed to investigate the anti-inflammatory effect of carvedilol and to study its effect on gastric mucosa. EXPERIMENTAL APPROACH: Lornoxicam (1.3mg/kg) or carvedilol (10mg/kg) was administrated orally 1h before histamine injection into animals of a histamine-induced paw edema model and orally daily for 11days into animals of a formaldehyde-induced arthritis model. Tumor necrosis factor-α and prostaglandin E2 were measured in animals of the formaldehyde-induced arthritis model. The effect of lornoxicam and carvedilol on gastric mucosa was assessed in normal rats and after induction of cold stress ulcer. RESULTS: Carvedilol succeeded in reducing hind paw edema in both histamine-induced paw edema and formaldehyde-induced arthritis and in reducing the elevated level of tumor necrosis factor-α and prostaglandin E2 nearly with near equal efficacy compared with lornoxicam. Carvedilol did not show any ulcerative effect on the gastric mucosa of normal rats, and its use was associated with an improvement of both the gross and histopathological pictures of gastric ulcers in animals of the cold stress ulcer model compared with lornoxicam treated rats. CONCLUSION: The current findings support the use of carvedilol both in the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. The use of carvedilol was not associated with any gastro-intestinal tract irritation.

Comparative study on the in vitro performance of blister molded and conventional lornoxicam immediate release liquitablets: accelerated stability study and anti-inflammatory and ulcerogenic effects.

CONTEXT: Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It shows limited solubility in the gastric pH, delayed bioavailability and pharmacodynamic effects with aggravated gastric side effects (due to longer residence in the stomach wall). OBJECTIVE: To enhance dissolution of lornoxicam in the gastric fluid and expectedly absorption and pharmacological action, with less ulcerogenic effects. MATERIALS AND METHODS: Formulation of immediate release (IR) lornoxicam liquitablets containing both liquid and solid release modulators (wetting agent, solubilizers and microenvironmental pH modifiers). Beside the traditional direct compression technique employed for the preparation of liquitablets a new technique, blister molding, was also used. The effect of the two different manufacturing methods on the fast release characteristics (rapid disintegration and dissolution) was studied. Stability and pharmacological activity of the optimum formula were also explored. RESULTS: Similarity factor pointed out the superiority of molding technique in enhancing dissolution of lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula showed negligible change in drug content and dissolution profiles over 12 weeks, significantly improved anti-inflammatory activity and significantly reduced gastric ulcerative effect over pure lornoxicam and commercial formula. DISCUSSION AND CONCLUSION: Blister molded lornoxicam liquitablet of improved dissolution and pharmacological activity and less gastric erosion was successfully prepared.