Study On Osmotic Pumping Tablet Of Ondansetron Hydrochloride

Ondansetron, a highly selective 5-HT3 receptor antagonist, reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs or high dose radiation. In this paper the solubility of ondansetron in water, simulated gastric liquid, simulated intestinal liquid and saturated sodium chloride solution was determined. The result showed that ondansetron was fit for osmotic pumping tablet, but sodium chloride could not be used as osmotic agent. The viscosity of cellulose acetate solution of different concentration in acetone was determined. It was found that the solution at the concentration of 2.5% could be used to coat tablets and after PEG400 was added to cellulose acetate solution, its viscosity increased. The properties of cellulose acetate free film prepared with three method (plate welding, plate spraying and pan coating) were investigated. It was found that after the film exposed to water, most of the PEG400 in it was leached out in 5 minutes, and that PEG400 could improve the water permeability of cellulose free film when its content in the film was higher than 10%, otherwise, its effect was little, and the aptitude of the improvement was different among the films produced with different method, the welding film was the largest, the pan-coating film the second, the plate-spraying film 3 (~) the third. The water permeability coefficient of the pan-coating free film was calculated, it was independent of the thickness of the film. The results of drug diffusion experiment showed that the free film was nearly not permeable to ondansetron. The drug releasing rules of potassium chloride osmotic pumping tablet(OPT) were investigated. The results indicated that if the tablet core contained no HPMC, the drug releasing rate of the preparation with its orifice downward was 6 times of the rate of the preparation with its orifice upward, but after HPMC was added to the core, this difference disappeared. It was found that the drug releasing rate increased prominently as the thickness of the coating reduced or the content of PEG400 in the coating increased, while the rotation speed of the dissolution tester, the size of the orifice and the hardness of the tablet core had little effect on the rate of drug releasing. The water permeability coefficient of coating film was calculated according to the drug releasing rate of the preparation, the results verified that the results of free film experiment could prognosticate the properties of the coating film. The ondansetron OPT was prepared by formulation screening and optimization. The in vitro drug releasing in 9 hours conformed to the model of zero order. The osmotic pumping was the main mechanism of drug releasing. The scanning electronic micrographs of the cellulose acetate film showed that there was great difference between welding film and pan coating film, confirmed the mechanism of film forming, piling up offogdrop, and the plasticization of PEG400. The stability of the preparation was investigated under 4400Lx light condition, 40C and 75%RH, room temperature and 60%RH, the results showed that the preparation was stable. Using HPLC to determine the plasma drug concentration and using 4...