Efficacy of a chitosan-curcumin mixture in treating indomethacin-induced acute gastric ulcer in rats

Background: Curcumin is claimed as a potent protectant against gastric ulcer (GU) induced by strong necrotizing agents including NSAIDs through its antioxidant, anti-inflammatory and gastroprotective activities. However, it was found to exert opposite effects to either delay ulcer healing or exacerbate ulcer inflammation through some curative mechanisms differently modified by curcumin dosage. Its ability in inhibiting the expression of COX-2 may also delay the healing of NSAIDs-induced GU. Recently, a topical chitosan-curcumin solution has been found to be a safe and potential alternative agent in treating oral ulcer. Therefore, an oral chitosan-curcumin mixture was developed and determined for its efficacy in treating NSAIDs-induced GU in rat. Methods: A chitosan (150 mg)-curcumin (20 mg) mixture with optimal gastric pH was developed. Indomethacin (30 mg/kg) was given orally to the rat and test preparations were administered orally at 5 h later and then every 24 h for two consecutive days. The sum of all gastric ulcerated areas (mm2) for each stomach was used as ulcer index. Gastric pro-inflammatory mediators and cytoprotective factors were determined. Results: An oral administration of a chitosan-curcumin mixture exerted a superior efficacy than curcumin, chitosan or lansoprazole (a standard antiulcer agent) in healing indomethacin-induced GU. It was revealed that the mixture exhibited the highest anti-oxidant, anti-inflammatory and gastric mucus producing activities including the high potency in down-regulating pro-inflammatory COX-2 and iNOS expression but up-regulating cytoprotective COX-1, nNOS and eNOS expression. Conclusion: The present findings indicated the benefit of a chitosan-curcumin mixture as a potential alternative agent in treating NSAIDs-induced gastric ulcer.

Chemoselective Demethylation of Methoxypyridine

A chemoselective demethylation method for various methoxypyridine derivatives has been developed. Treatment of 4-methoxypyridine with L-selectride in THF for 2 h at reflux temperature afforded 4-hydroxypyridine in good yield; no reaction to anisole occurred. The utility of our method was demonstrated by the efficient synthesis of the metabolic substances of the antiulcer agent omeprazole. Chemoselective demethylation at the site of 3,5-dimethyl-4-methoxypyridine in the presence of 4-methoxybenzimidazole was achieved.

Stability Indicating UV Spectrophotometric Method for Estimation of Omeprazole and Its Application to Content Uniformity Testing

Omeprazole is a most commonly used antiulcer agent in clinical practices. A least time consuming efficient and simple ultraviolet spectrophotometric method for the assay of omeprazole has been developed. The assay was based on the ultraviolet absorbance maxima at about 217.80 nm wavelength of omeprazole using sodium hydroxide as the solvent. In the present study comprehensive stress degradation was carried out according to ICH Q1 (R2) guidelines. The drug was subjected to acidic (0.1N HCl), basic (0.1N NaOH), oxidative (1% H2O2), photolytic and thermal degradation conditions. The developed UV spectrophotometric method showed high degradation under acidic condition, moderate degradation under basic, photolytic and thermal conditions. But it was relatively stable under oxidative conditions. The pathway for degradation has been proposed. The method was validated for Linearity, Accuracy, Precision, Specificity, Ruggedness and Robustness. The method shows good linearity in the range of 2-20μg/ml. The LOD and LOQ were found to be 0.1 μg/ml and 1.1 μg/ml. The %RSD was found to be with in limit i.e. less than 2%.The mean recovery of placebo was 100.68%. It can be concluded that the developed procedure is valid and can be applicable for determination of content uniformity for available brands of omeprazole. This method is applicable for the daily routine quality control quantitative analysis of omeprazole.