星点设计-效应面法优化复方氯雷伪麻缓释片的缓释片芯处方

Optimization of the Formulation of Loratadine Pseudoephedrine Sulfate Sustained-release Tablets by Central Composite Design-response Surface Methodology

目的:优化复方氯雷伪麻缓释片的缓释片芯处方。方法:以氯雷他定加入包衣层并包衣硫酸伪麻黄碱片芯制备复方氯雷伪麻缓释片。采用星点设计-效应面法优化硫酸伪麻黄碱片芯处方,以单硬脂酸甘油酯(GM)和羟丙甲纤维素(HPMC)K15M用量为考察因素,以硫酸伪麻黄碱1、6、12 h的累积释放度为指标,通过重叠等高线图确定优化处方,并进行处方验证。结果:氯雷他定与欧巴代包衣粉按1∶3比例混合包衣成为速释层;硫酸伪麻黄碱片芯作为缓释层,其处方为每100片(600 mg/片)含硫酸伪麻黄碱12 g、GM 16.72 g、HPMC K15M 20.95 g、微晶纤维素9.73 g、硬脂酸镁0.6 g。优化处方所制制剂中氯雷他定15 min的累积溶出度为87.2%,硫酸伪麻黄碱1、6、12 h的累积释放度分别为34.20%、74.32%、94.60%。结论:缓释片芯处方合理、可行,所制备的复方氯雷伪麻缓释片具有缓释作用。

OBJECTIVE： To optimize the formulation of sustained-release tablet core of Loratadine pseudoephedrine sulfate sustained-release tablets. METHODS： Pseudoephedrine sulfate tablet core was coated with loratadine by adding loratadine into coating layer to prepare Loratadine pseudoephedrine sulfate sustained-release tablets. The formulation of pseudoephedrine sulfate core was optimized by central composite design-response surface methodology with the amount of GM and HPMC K15M as factors using 1, 6 and 12 h accumulative release rate of pseudoephedrine sulfate as index. The optimal formulation was selected by using overlay contour plots and then verified. RESULTS ： Loratadine and opadry coating powder with ratio of 1 ： 3 were mixed and coated on the tablets as quick release layer. Pseudoephedrine sulfate tablet core was used as sustained-release layer. The formulation of sustained-release tablets was as follows： pseudoephedrine sulfate 12 g, GM 16.72 g, HPMC K15M 20.95 g, microcrystalline cellulose 9.73 g, magnesium stearate 0.6 g per 100 tablets （600 mg/tablet）. Accumulative dissolution rate of loratadine was 87.2% at 15 min. The accumulative release rates of pseudoephedrine sulfate were 34.20%, 74.32% and 94.60% at 1, 6 and 12 h respectively. CONCLUSIONS： The formulation of sustained-release tablet core is reasonable and feasible, and Loratadine pseudoephedrine sulfate sustained-release tablet can achieve sustained release.