目的 根据马来酸曲美布汀水溶性小、口服吸收生物利用度低、生物半衰期较短(2.7 h)的特点,本实验将其制成缓释滴丸,以期达到缓释、降低血药浓度波动和减少服用次数的效果。方法 以聚乙二醇(PEG)类、硬脂酸(SA)和单硬脂酸甘油酯(GMS)为基质用熔融法制备马来酸曲美布汀(trimebutine maleate)缓释滴丸。以药液流动性、易滴制程度、下沉速度、圆整度为指标进行处方初步筛选,通过溶出实验,以释放区间优化法筛选出最佳处方,最终通过正交设计实验,以圆整度、丸重差异、累积释放度进行综合评分确定最佳工艺。结果 筛选出最佳处方为TM-PEG4000-PEG6000-SA-GMS= 2.4∶1.2∶1.2∶1.2∶1.2,最佳工艺条件:料液温度为75 ℃,冷凝温度30→5 ℃,滴距为5 cm。制得的马来酸曲美布汀缓释滴丸体外释放行为符合零级和Hugich方程。结论 本方法制备的马来酸曲美布汀缓释滴丸成型性较好,体外释放较为缓慢,能够使血药浓度波动降低,服用次数减少,符合临床治疗需要。

OBJECTIVE According to the feature that trimebutine maleate has poor aqueous solubility, low bioavailability when taken orally, short biological half-life(2.7 h), sustained-release dropping pills were prepared to achieve release slowly, reduce the blood drug concentration fluctuations and decrease frequency of use. METHODS Polyethylene glycol, stearic acid and glycerin monostearate were used as matrix to prepare trimebutine maleate sustained-release dropping pills by melting method. Drug liquidity, difficulty level of preparation, settling velocity and roundness were used as evaluation indexes to conduct preliminary prescription screening. The optimal formulation was selected with interval optimization method of releasing degree by dissolution test. The optimum technology was finally confirmed in orthogonal test by comprehensive scores including roundness, pills weight difference and accumulative releasing. RESULTS The proportion of prescription was TM-PEG4000-PEG6000-SA-GMS= 2.4∶1.2∶1.2∶1.2∶1.2. The optimum technological condition: the temperature of drug liquid was 75 ℃, the freezing temperature was 30→5 ℃, the distance to the condensed fluid was 5 cm. Release behavior in vitro of trimebutine maleate sustained-release dropping pills accorded with first order equation and Hugich equation. CONCLUSION Formability of trimebutine maleate sustained-release dropping pills was good, release behavior in vitro was slow, blood drug concentration fluctuations was decreased and frequency of use was reduced, trimebutine maleate sustained-release dropping pills with this method meet the clinical needs.