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目的制备呋喃妥因缓释微丸,研究药物的晶型稳定性并评价微丸的缓释作用。方法通过湿法研磨技术制备呋喃妥因纳米混悬液;以差示扫描量热法(differential scanning calorimeter,DSC)及粉末X射线衍射法(powder X-ray diffraction,PXRD)研究药物晶型变化;采用液相层积技术制备呋喃妥因缓释微丸;通过体外释放度筛选处方;采用UPLC-MS/MS法测定Beagle犬血浆样品。结果药物经湿法研磨后,粒径由约40μm降至455 nm,晶型稳定。体外释放试验结果表明,在模拟体内胃肠道消化液环境的溶出介质中该制剂在释放前期符合零级释放,后期则符合一级释放。体内试验结果表明,呋喃妥因缓释微丸相对于市售肠溶包衣片的生物利度为143.8%;前者的消除半衰期(t1/2)及平均滞留时间(mean residence time,MRT)均较后者有所延长。结论湿法研磨技术可显著降低药物粒径,提高溶出速率,药物体外释放符合要求,该微丸具有一定缓释效果。
Objective To prepare nitrofurantoin sustained-release pellets, study its crystal stability and evaluate the sustained-release effect of pellets. Methods The wet-grinding technique was used to prepare the nitrofurantoin nanocomposite suspension. The changes of drug crystal form were studied by differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) Phase-delamination technique was used to prepare nitrofurantoin sustained-release pellets, and the prescriptions were selected by in vitro release. The plasma samples of Beagle dogs were determined by UPLC-MS / MS. Results After the drug was wet-milled, the particle size decreased from about 40 μm to 455 nm and the crystal form was stable. The results of in vitro release test showed that in the dissolution medium of gastrointestinal tract digestive juice simulated in vivo, the preparation meets the zero-order release in the early stage of release and the first-stage release in the late stage. The in vivo test results showed that the bioavailability of nitrofurantoin sustained-release pellets was 143.8% compared with that of the enteric-coated tablets. The former half-life (t1 / 2) and mean residence time (MRT) Has been extended. Conclusion The wet grinding technique can significantly reduce the drug particle size and increase the dissolution rate. The in vitro release of the drug meets the requirements and the pellet has a certain sustained release effect.