本文選題：恩諾沙星　切入點：緩釋顆粒　出處：《武漢工程大學》2015年碩士論文

【摘要】：恩諾沙星是廣譜抗菌素,屬于喹諾酮類第三代藥物,由于其高效、低毒的抗菌特點,在1996年被FDA批準為動物專用藥,也是第一個獲國際認可的動物專用抗菌藥。普通的恩諾沙星制劑因味苦口感不佳或頻繁給藥等導致動物的應激反應,出現(xiàn)拒食現(xiàn)象,而使它們因各種細菌感染的疾病得不到很好地預防和治療,降低了成活率。為了掩蓋恩諾沙星的苦味和提高治療效果,本文結(jié)合緩釋材料的特性,制備了12小時內(nèi)緩慢釋放的恩諾沙星緩釋顆粒劑,以期達到減少給藥次數(shù),同時由于降低了藥物溶出速度而起到改善藥物口感的作用。具體進行了以下幾方面的工作:建立了恩諾沙星緩釋顆粒劑的含量測定方法和體外累積釋放度的測定方法。通過處方前研究,采用單因素實驗和正交實驗,以相似因子f2值為評價指標,篩選出了最佳制備處方為:恩諾沙星20%、羥丙基甲基纖維素k100(HPMCk100)25%、硬脂酸8%、乳糖35%、粘合劑為5%聚乙烯吡咯烷酮k-30(PVPk-30)醇溶液;制備工藝為:以親水凝膠骨架材料羥丙基甲基纖維素(HPMCk100)與蠟質(zhì)材料硬脂酸的混合物為骨架材料,采用溶劑熔融法,先制備恩諾沙星的固體分散體,再與乳糖、聚乙烯吡咯烷酮K-30(PVPk-30)等輔料混合制備顆粒,即得具有緩釋效果的恩諾沙星顆粒劑。并以最優(yōu)處方制備三批放大樣,對最優(yōu)處方和工藝進行驗證。根據(jù)相關(guān)標準對恩諾沙星緩釋顆粒劑的質(zhì)量進行研究,系統(tǒng)地考察了各項質(zhì)量指標,如粒度、性狀、鑒別、有關(guān)物質(zhì)、藥物含量測定和累計釋放度測定等,結(jié)果表明該制劑的制備工藝可行,產(chǎn)品質(zhì)量穩(wěn)定,可以為后期擬定質(zhì)量標準提供科學、合理、有效的依據(jù)。最后考察了恩諾沙星緩釋顆粒劑的穩(wěn)定性。影響因素實驗結(jié)果表明,制備的恩諾沙星緩釋顆粒在相對濕度75%的條件下放置10天,顆粒略有吸濕,而在60℃高溫和4500Lx±500Lx強光照條件下,樣品質(zhì)量穩(wěn)定,各項指標均無明顯變化。模擬市售包裝的恩諾沙星緩釋顆粒在40±2℃溫度,65%±5%的相對濕度的實驗環(huán)境下放置6個月,進行加速試驗;在25±2℃溫度,60%±5%的相對濕度環(huán)境下放置6個月,進行長期實驗,結(jié)果顯示樣品的各項質(zhì)量均未發(fā)生明顯變化,表明該產(chǎn)品質(zhì)量比較穩(wěn)定。
[Abstract]:Enrofloxacin is a broad-spectrum antibiotic, belonging to the third generation of quinolones. Because of its high efficiency and low toxicity, enrofloxacin was approved by FDA as animal medicine in 1996. It is also the first internationally recognized animal-specific antimicrobial agent. Common enrofloxacin formulations, which suffer from poor taste and bitter taste or frequent administration of drugs, cause stress reactions in animals and lead to anti-feeding phenomena. In order to cover up the bitter taste of enrofloxacin and improve the therapeutic effect, this paper combines the properties of slow release material, in order to cover up the bitterness of enrofloxacin and improve the therapeutic effect. Slow release of enrofloxacin granules was prepared within 12 hours in order to reduce the frequency of administration. At the same time, it can improve the taste of the drug by reducing the dissolution rate of the drug. The following work has been done: the method of determination of the content of enrofloxacin sustained-release granules and the determination of cumulative release in vitro have been established. Methods. Through the pre-prescription study, By using single factor experiment and orthogonal experiment, the best preparation prescription of enrofloxacin 20, hydroxypropyl methyl cellulose k100 HPMCk100, stearic acid 8, lactose 35 and binder 5% polyvinylpyrrolidone k-30PVPk-30 alcohol solution was selected. The preparation process was as follows: the mixture of hydrophilic gel framework HPMCk100) and waxy stearic acid was used to prepare enrofloxacin solid dispersion, then lactose, by solvent melting method. Poly (vinylpyrrolidone) K-30 (PVPk-30) and other excipients were mixed to prepare particles, namely enrofloxacin granules with slow-release effect, and three batches of magnified samples were prepared with the best formulation. The quality of enrofloxacin sustained-release granules was studied according to the relevant standards. The quality indexes, such as particle size, properties, identification, related substances, were systematically investigated. The results showed that the preparation process of the preparation was feasible and the product quality was stable, which could provide a scientific and reasonable method for the later formulation of the quality standard. Finally, the stability of enrofloxacin sustained release granules was investigated. The experimental results showed that the prepared enrofloxacin sustained release granules were slightly hygroscopically absorbed at 75% relative humidity for 10 days. However, under the conditions of high temperature of 60 鈩，

本文編號：1662368