| Famotidine is the third generation of potent H2receptor antagonist. Through uniting with the H2receptor in the cell of stomach, famotidine manages to inhibit the secretion of gastric acid. It is mainly used for gastric, duodenal ulcer, reflux esophagitis, upper gastrointestinal bleeding and other diseases on clinical. At present, it is usually in the forms of tablet and capsule as the common dosages, which results in low bioavailability (<50%) since the drug could not be maintained in the stomach for enough time. And due to the slow accumulation of the stomach cells, the effectiveness of the drug can not be fully reached. Upon this consideration, this paper tries to study the gastric floating, to make the model drug-famotidine staying long enough in the stomach effectively, to reduce the impact from gastric emptying, and to have better effect in the treatment of stomach disease.Relevant literature was studied extensively before a series of experiments were carried out in order to obtain the composition of the pellets’prescription. Mixing with the adjuvant materials MCC, which is good for formability, and octadecanol, which can reduce the density, famotidine core pellets were prepared by extrusion-spheronization method. Then it was coated in three layers of fluid bed coating equipment with three separate functions. The effects of the composition as well as the amount of coating liquid on the floating behavior and the releasing characteristics were also investigated thereafter. After coated by the mixture of Eudragit RL and RS (1:3in weight), sodium bicarbonate and Eudragit RL successively, the results showed that the obtained pellets had excellent features, such as the uniform size, which is1.92mm of mean diameter, and the satisfactory roundness, which is0.92of aspect ratio. The pellets could float within2min and keep floating for more than24h upon0.1mol-L"1hydrochloric acid.Additionally, this paper studies the famotidine microspheres prepared by the emulsion solvent evaporation method. Through examining the type and dosage of different carriers, oil phase, composition of emulsifier, the volume and PH, temperature of aqueous phase and the amount of three citric acid ethyl ester, EUDRAGIT s100was finally confirmed the as the drug carrier. The ratio of the carrier to the drug is8:1. The ratio of ethanol to dichloromethane is10:6. Based on the following matches of different experimental conditions, the content of three citric acid ethl ester being0.2g, the temperature beings40℃, the volume beings150ml, and the emulsifier being PVA124, the results showed that the yield is47.66%, drug loading capacity is7.70%, the average entrapment efficiency is69.37%, the floating behavior is good and90%microspheres is still floating on the surface within24h. Through the method of dialysis to test the releasing characteristics, it is shown that the dosage releases80%of the total dose with12h continuously, proving that the result of the experiment coincide with purpose of the experiment.Finally, we tried to analyze the pharmacokinetics of the pellets and microspheres by carrying experiments on rats. Rats were divided into three groups, the original group, the group injected with pellets (the pellets) and another group injected with microspheres (the microspheres). Through taking blood from the canthus of the rats at specific times, by using protein deposition method to deal with the plasma samples, and by HPLC to test the blood drug level at the specific times, the final conclusion, which was statistical by DAS, showed that both pellets and microspheres have good slow-releasing effect, which is equal to bio-tech drugs. |
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