盐酸哌甲酯缓释微丸胶囊剂的研制与体外释放

Preparation and in vitro Release Behavior of Methylphenidate Hydrochlori Desustained-release Capsules

目的制备一种盐酸哌甲酯(MPH)缓释微丸胶囊剂,并与进口控释片专注达体外释放情况进行比较研究。方法利用流化床包衣技术制备一种含有3种不同释药速率微丸的MPH缓释微丸胶囊剂:将部分载药微丸包保护层后制成速释微丸;以乙基纤维素(Surelease)为缓释材料制备单层缓释微丸;通过内包溶胀层(欧巴代-7006,主成分为低黏度羟丙基甲基纤维素(HPMC),外加控释层制备具有时滞的双层择时缓释微丸。在模拟胃肠道pH值介质中比较自制胶囊剂与控释片的体外释药情况。结果载药微丸实际载药量6.85%。单层缓释微丸包衣增重14%;双层择时缓释微丸溶胀层包衣增重16%,控释层包衣增重22%,时滞约3.5 h。3种微丸按以下比例混合后装胶囊:速释微丸含MPH 22%,单层缓释微丸含MPH 39%,双层择时缓释微丸含MPH 39%。该胶囊剂1 h释放可达25%,4 h释放约50%,12 h释放>95%。两制剂在模拟胃肠道介质中的释放曲线相似。结论制备出一种由3种微丸组成的,能连续12 h释药的MPH缓释微丸胶囊剂,其工艺简单,与进口控释片专注达有相同的体外释放效果。

Objective To prepare a kind of methylphenidate hydrochloride （MPH） sustained-release capsule, and make a comparative study of controlled release tablets in vitro with imported drug release. Methods Using fluidized bed coating technology, we prepared a kind of capsule which contains 3 different release-rate pellets. Drug-loaded pellets packed protective layer made of as the quick-release pellets; use ethylcellulose （Surelease ~） as coating material to make sustained-release pellets. Double-layer extended-release pellets were prepared using Opadry-7006 （ the main component of low-viscosity HPMC） as inner swelling layer and Surelease~ as outer controlled release layer. Results Pellets actual drug loading was 6.85%. The technology and formulation of pellets were optimized. Weight of sustained- release pellets coating increased 14%. Weight of double-layer extended-release pellets which with swelling layer coating increased 16%, and the weight of controlled release layer coating increased 22%. The double-layer pellets had a 3.5-hour lag time. Three kinds of pellets were mixed in the following proportions loaded capsules： quick-release pellets （containing MPH 22%）; sustained-release pellets （containing MPH 39%）; double-layer extended-release pellets （containing MPH 39%）. The 1-hour release of MPH from the self-made preparation was about 25%; 4-hour release was about 50%; 12- hour release was more than 95%. Conclusions We prepared a kind of sustained-release capsule which could continue releasing MPH for 12 hours. This preparation process is simple. The self-made capsule with reference preparation has the same effect on in vitro release.