甲磺酸二氢麦角碱缓释片的制备与体外释放特性研究

Study on Preparation and in vitro Release Characteristics of Ergoloid Mesylate Sustained-release Tablets

目的:制备甲磺酸二氢麦角碱缓释片,研究其体外释放特性。方法:以羟丙甲基纤维素(HPMC-K4M)为骨架材料,采用湿法制粒制备甲磺酸二氢麦角碱缓释片。以释放速率、累积释放度为指标,以载药材料(HPMC-K4M)、填充剂(乳糖、磷酸氢钙)和微环境p H调节剂(酒石酸)的用量为因素,采用单因素试验和正交试验对甲磺酸二氢麦角碱缓释片处方进行优化并验证;采用《中国药典》释放度测定方法比较进口和最优处方所制甲磺酸二氢麦角碱缓释片的体外释放特性。结果:最优处方为甲磺酸二氢麦角碱2.5 mg,HPMC-K4M 40 mg,乳糖70 mg,磷酸氢钙80 mg,酒石酸40 mg;所制甲磺酸二氢麦角碱缓释片可体外持续释药12h以上,12 h累积释放度为97.1%,与进口片剂比较累积释放度无明显变化,体外释药行为符合Higuchi方程。结论:成功制得具有缓释作用的甲磺酸二氢麦角碱缓释片。

OBJECTIVE：To prepare Ergoloid mesylate sustained-release tablets and study their in vitro release characteristics.METHODS：Wet granulation method was adopted to prepare Ergoloid mesylate sustained-release tablets with hydroxypropylmethylcellulose K4M（HPMC-K4M）as the matrix. Single factor test and orthogonal test were performed to optimize the formulation with release rate and accumulative drug release rate as the index and the amount of the carrier（HPMC-K4M）,filler（lactose,dibasic calcium phosphate）and microenvironmental p H-modifier（tartaric acid）as factors,and it was verified. Release determination method as specified in the Chinese Pharmacopoeia was employed to compare the in vitro characteristics between the Ergoloid mesylate sustained-release tablets imported and those prepared on the basis of optimal formulation. RESULTS：The optimal formulation was as follows as ergoloid mesylate of 2.5 mg,HPMC-K4 M of 40 mg,lactose of 70 mg,dibasic calcium phosphate of 80 mg,tartaric acid of 40 mg. For the Ergoloid mesylate sustained-release tablets prepared,the drug could be released in vitro for over 12 h,during which the accumulative drug release rate reached 97.1%,without any obvious difference from that of the imported tablets. The in vitro drug release of the tablets prepared was in conformity with Higuchi equation. CONCLUSIONS：The Ergoloid mesylate sustained-release tablets have been prepared successfully.