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% （ <> t 0.05 ）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（ <> t lag-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 <> t 0.9 约为 30 min ，第二脉冲剂量的 <> t 0.9 约为 45 min ， <> t lag-time 约为 150 min 。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。
Abstract
OBJECTIVE To prepare a double pulse control release pellets of zolpidem tartrate and investigate the dissolution influence factor in vitro. METHODS The kind and amount of disintegrant were screened using uniform design and single factor design. Core contented drug was prepared by Extrusion-spheronization. The surface was improved using coating lactose with Pharmacoat 606. The single pulse release pellets were prepared by coating a control release layer with Ethvlcellulose aqueous dispersion （Surelease E-7-19040）. The double pulse pellets were prepared by loading drug and coating film with Pharmacoat 606. The times of beginning and completing of dissolution were defined when cumulative percentages of drug dissolution were 5.00% （t 0.05）and 90.00%（t0.9）. The time was as lag-time if the cumulative percentage of drug dissolution was less than 5.00%. RESULTS ■Croscamellose sodium was a suitable disintegrant. t 0.9 of the first and second pulse dosage were about 30 and 45 min respectively. t lag-time was about 150 min. The factors such as disintegrant amount, pellet diameter, weight percentage of control release layer, the progress of finishing, drug contented layer loading ,film coating will affect the in vitro dissolution. The pH value of dissolution medium show no influence on the dissolution in vitro. CONCLUSION The pellets have an ideal double pulse release.
关键词
酒石酸唑吡坦 /
双时释药制剂 /
双脉冲释药系统
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Key words
zolpidem tartrate /
timed dual release dosage form /
double pulse drug delivery system
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参考文献
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（ 收稿日期 ： 2008-12-01 ）
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