Study On The Sustained –release Granules Of Enrofloxacin

Enrofloxacin, as the third generation quinolone antimicrobial agent, was the first international recognition of veterinary drug approved by the FDA in 1996. It showed excellent features, such as a broad antimicrobial spectrum, hypotoxicity and effective antibacterial activity against some kinds of bacteria, and was widely used in clinic by injection or orally. Meanwhile, due to the stress response in an animal produced by poor taste or frequent dosing, the bioavailability was low. In this thesis, we had successfully prepared sustained release granule of enrofloxacin with slow release technique, which decreased the dosing frequency, and covered up the bitter taste of the drug due to a low rate of dissolution. The main contents are described as follows:The methods for determination and cumulative dissolution in vitro of sustained release granule of enrofloxacin were established by studying the pre-formulation. Using f2(the similarity factor serving as evaluation indicator), the best prescription was evaluated by the orthogonal experiment and the single-factor research. The optimal prescription was(100%): enrofloxacin: 20%; HPMCk100: 25%; stearic acid: 8%; lactose: 35%; PVPk-30: 5%, which could be further confirmed by testing amplification ratio of the samples. The preparation processes: By means of the solvent-melting method, the solid dispersion of enrofloxacin was synthesized by using a mixture of hydrophilic gel material-HPMCk100 and wax material-stearic acid as framework material. And then mixed with lactose and PVPk-30 as excipients for pelletization, namely sustained release granule of enrofloxacin.In addition, the research of quality standard, including granularity, trait, identification, related substances, and the determination of content and cumulative dissolution in vitro and so on, was investigated systematically. These results revealed that the preparation process was feasible and the quality of the product was also stability, which provided scientific, reasonable and effective guidance for quality standard.Finally, in order to study the stability of sustained release granule of enrofloxacin, the special test, such as influencing factors test, the accelerated and long-term tests, could be done. The results of influencing factors test indicated that sustained release granule of enrofloxacin became slightly hygroscopic after stored at room temperature with relative humidity 75% for 10 days. Under illumination with a power intensity of 4500Lx±500Lx at 60℃, the observed indexes were not significantly changed. Meanwhile, the results coming from the accelerated and long-term tests demonstated that, sustained release granule of enrofloxacin with simulation of commercially available packaging measured under the temperature 40+2 ℃, relative humidity 65%+5% for six months or temperature 25+2℃, relative humidity 60%+5% for 12 months also exhibited excellent stability.