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目的研制酒石酸唑吡坦双脉冲控释微丸,考察微丸体外溶出度影响因素。方法用均匀设计及单因素实验设计筛选崩解剂种类和用量,确定载药丸心处方;用挤出滚圆法制备载药丸心,并依次用流化床技术在载药丸心表面以羟丙甲纤维素(Pharmacoat 606)加载乳糖进行包衣,光洁化表面;用乙基纤维素水分散体(Surelease E-7-19040)进行控释包衣制备成单脉冲微丸,单脉冲微丸表面以Pharmacoat 606加载药物后进行薄膜包衣,制备成双脉冲微丸。以溶出度达5%(t0.05)和90%t0.9)为脉冲剂量开始释放和完全释放的参考指标,以持续释放小于总剂量5%的释药时间作为迟滞时间(tlag-time);同时考察体外溶出度的影响因素。结果交联羧甲基纤维素钠是最合适的崩解剂,优化用量为50%,第一脉冲剂量的t0.9约为30min,第二脉冲剂量的t0.9约为45min,tlag-time约为150min。微丸粒径的大小,崩解剂的用量,光洁化处理时的包衣增重,控释层衣膜的增重程度,单脉冲微丸表面含药层的加载,双脉冲微丸表面的薄膜包衣都对微丸的溶出有影响;但不受溶出介质pH值的影响。结论所制得的双脉冲微丸具有良好的双脉冲释放效果。
Objective To develop Zolpidem tartrate dual-pulse controlled-release pellets and investigate the influencing factors of in vitro dissolution of pellets. Methods Using uniform design and single-factor experimental design to screen the type and dosage of disintegrant to determine the prescription of loaded pills. The pellets were prepared by extrusion-spheronization method, (Pharmacoat 606) was loaded with lactose for coating, smooth the surface; controlled release coating with ethylcellulose aqueous dispersion (Surelease E-7-19040) prepared into single pulse pellets, single pulse pellets surface Pharmacoat 606 after drug loading film coating, prepared into double pulse pellets. A reference index of 5% (t0.05) and 90% t0.9 of dissolution for pulsed dose initiation and complete release, sustained release of less than 5% of the total release dose as the tlag-time, At the same time, the influencing factors of in vitro dissolution were investigated. Results Croscarmellose sodium was the most suitable disintegrant. The optimal dose was 50%. The first pulse dose was about 90 minutes, the second pulse dose was about 90 minutes, the tlag-time About 150min. The size of the pellets, the amount of the disintegrant, the weight gain of the coatings during smoothing treatment, the degree of weight gain of the controlled release coating film, the loading of the drug-containing layer on the surface of the single pulse pellets, the surface of the double pulse pellets The film coating has an impact on the dissolution of the pellets; however, it is not affected by the pH of the dissolution medium. Conclusion The obtained double pulse pellets have a good double pulse release effect.