Formulation of stomach-specific floating microparticles of nizatidine and their radiographic evaluation

Nizatidine is an anti-secretogogue and a gastroprotective drug with a half-life of 1-2 h and is well absorbed in the stomach. This study aimed to optimize the process and develop floating microparticles of nizatidine that are based on low methoxyl pectin. Oil-in-oil dispersion method and Taguchi orthogonal array design were employed, and the prolonged residence time of the microparticles in the stomach was demonstrated. The constraints for independent variables, viz. A-polymer, B-internal solvent volume, C-surfactant, D-stirring rate and E-stirring time were set to generate the experimental runs. Particle size, percentage yield, micromeritic properties, entrapment efficiency, in vitro buoyancy and in vitro release were characterized. Surface morphology, zeta potential, in vitro release kinetics and in vivo floating performance of the optimized formulation was examined. The microparticles were free-flowing, irregular in shape and had a mean particle size distribution of 73-187 µ. Low methoxyl pectin played a predominant role in achieving buoyancy and optimum gastric retention for the modified release of the drug, suggesting Korsmeyer-Peppas model as the possible release mechanism. In vivo radiographic study in rabbits revealed that the drug was retained in the stomach for a period of 6 h. These results indicate that nizatidine floating microparticulate system provides modified drug release for the effective treatment of gastric ulcer

Changes in the effects of nizatidine and famotidine on cardiac performance after pretreatment with ranitidine.

This was an open, randomized study of the cardiovascular effects of the histamine H2 receptor antagonists ranitidine, famotidine, and nizatidine after single oral doses alone or in combination in healthy volunteers. When compared with placebo ranitidine (450 mg) did not have any haemodynamic effects. Nizatidine (300 mg) caused significant falls in heart rate and cardiac output. Famotidine (40 mg) caused significant falls in stroke volume and cardiac output and an increase in pre-ejection period. Pretreatment with ranitidine abolished the haemodynamic effects of nizatidine and caused a time-shift of 2 h in the onset of the cardiovascular effects of famotidine. The difference in the results for nizatidine and famotidine can be explained by the longer half-life of famotidine. Vascular effects are assumed to be responsible for impairment of cardiac performance by famotidine.

The effect of nizatidine on neuromuscular transmission.

The effect of the H2-receptor antagonist, nizatidine, on neuromuscular transmission was investigated using sciatic nerve-gastrocnemius muscle preparations of rat in vivo. Nizatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and the aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on preparations stimulated at high frequency. The neuromuscular blockade induced by nizatidine is reversed by 4-aminopyridine but not by dimaprit.