盐酸地尔硫爆破型脉冲控释片研究  

STUDIES ON PULSATILE RELEASE TABLETS OF DILTIAZEM HYDROCHLORIDE IN EXPLOSION WAY

作　　者：范田园[1] 魏树礼[1] 严文伟[1] 丁武孝 

机构地区：[1]北京大学药学院药剂学系,北京100083

出　　处：《药学学报》2002年第3期221-225,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 39770 878)

摘　　要：目的　以盐酸地尔硫为 (diltiazemhydrochloride,DIL)模型药物 ,研制爆破型脉冲控释片并考察其体内外脉冲释药特性。方法　以乙基纤维素和丙烯酸树脂 (EudragitL)为包衣材料 ,采用薄膜包衣法 ,制备含盐酸地尔硫6 0mg的脉冲控释片。通过体外释放度实验 ,考察了处方因素对脉冲控释片体外释放的影响 ;通过吸水实验确定了脉冲控释片的释药机理 ;以高效液相色谱法测定 8名受试者的体内血药浓度 ,研究脉冲控释片的体内药代动力学和生物利用度。结果　片芯处方、包衣组成和包衣厚度影响盐酸地尔硫的脉冲释放。该制剂在体外延迟释放时间T1 0 为 4 4h ,释放至最大的时间Trm 为 8 0h ,脉冲释放时间Trm - 1 0 为 3 6h ;其体内的延迟释放时间Tlag为 4 9h ,达峰时间Tmax为 8 0h ,从开始释放到达峰的时间Tpsi为 3 1h。脉冲控释片的相对生物利用度为 10 5 %。结论　盐酸地尔硫爆破型脉冲控释片在体内外都具有脉冲释放特性。AIM To investigate the preparation of pulsatile release tablets, the release of the drug in vitro and the pharmacokinetics in vivo . METHODS Diltiazem hydrochloride (DIL) was used as model drug. The pulsatile release tablets were prepared by film-coated method using ethylcellulose and Eudragit L. The effect of formulation on pulsatile release of diltiazem hydrochloride was investigated under release rate test. The mechanism of pulsatile release of drug was proved by the test of water-uptake. The pharmacokinetic and bioavailability study in eight human subjects was performed by HPLC method. RESULTS The release of diltiazem hydrochloride effected by the formulation of the core tablets and the composition and thickness of the coating film. In vitro , the delayed-release time T 10 was 4 4 h, the maximum release time T rm was 8 0 h and the pulsed-release time T rm-10 was 3 6 h. In vivo , the delayed-release time T lag was 4 9 h, the peak time was 8 0 h and the pulsed-release time was 3 1 h. The relative bioavailability was 105%. CONCLUSION The release of drug from pulsatile release tablets of diltiazem hydrochloride was shown to be in pulsed way both in vitro and in vivo .

关 键 词：爆破型脉冲控释片 盐酸地尔硫ZHUO 药代动力学 

分 类 号：R944.9[医药卫生—药剂学] R969.1[医药卫生—药学]