左乙拉西坦缓释片的处方及制备工艺研究

A new formulation and preparation of extended-release tablet of levetiracetam

目的：制备左乙拉西坦缓释片,并对其处方进行深入研究。方法：以自制品的释放曲线及其与左乙拉西坦参比制剂（Keppra XR）释放行为相似因子（f2）为考察指标,选取缓释片最优处方组成,确定制备工艺关键步骤,并与参比制剂的释放曲线进行对比,对左乙拉西坦的自制处方进行评价。结果：自制左乙拉西坦缓释片的处方为：左乙拉西坦1 000 mg、山嵛酸甘油酯363.2 mg、乳糖25.5 mg、硬脂酸镁21.3 mg、片重1 420.0 mg。供试品溶液浓度在0.2~1.2 mg·m L-1范围内,浓度与峰面积线性关系良好,r=0.998 1。本品释放度测定方法的平均回收率为99.08%,表明本方法准确度良好。精密度试验测得相对标准偏差（RSD）为0.6%,供试品在室温条件下放置8 h内保持稳定。结论：通过低熔点缓释辅料山嵛酸甘油酯及其最优处方组成和熔融制粒工艺等得到的自制品与市售参比制剂在p H 4.5醋酸盐缓冲液释放介质中的释放行为基本相似。

Objective： To prepare the new levetiracetam extended-release tablet and investigate its formula- tion. Methods： The formulation of levetiraeetam extended-release tablet was optimized by determining the parame- ter of the similar factor （f2） between the test tablets and reference product （ Keppra XR）. The optimal formulation was obtained, and the critical steps of the preparation process were optimized. The release curve of levetiracetam extended-release tablet was compared with that of reference product. Results ： The prescription of levetiracetam ex- tended-release tablet was levetiracetam 1 000 mg, behenate 363.2 mg, lactose 25.5 mg, and magnesium stearate 21.3 mg. Its weight was 1 420.0 mg. Linear relationship was found in the concentration range of 0.2 - 1.2 mg·mL-1 in the test sample solution, r = 0. 998 1 between concentration and peak area. The average recovery rate in dissolution test of this product was 99.08% , showing a good accuracy of this method. Precision experiments showed that the relative standard deviation （RSD） was 0. 6%. Solution stability experiment result showed that the test samples placed within 8 h remained stable at room temperature. Conclusion： The test tablets, which are pre- pared with the optimal formulation （low melting point slow-release accessories： glyceryl behenate） and melting granulating process. The drug solution properties are stable, and similar to those of the reference products in pH 4.5 acetate buffer dissolution.