基于质量源于设计(QbD) 理念，运用鱼骨分析图筛选盐酸奈福泮双相释放双层片的关键质量属性(CQAs)，并采用失效模式和影响分析法(FMEA)、Plackett-Burman 设计(PBD) 对各关键工艺参数(CPPs) 进行风险评估及筛选优化。采用Box-Behnken 设计(BBD) 对CPPs 进行优化，建立统计模型；采用Minitab 及Design-Expert 软件对所得试验数据进行分析，筛选盐酸奈福泮双相释放双层片的优化处方。结果表明，制粒目数、释放调节剂用量和缓释材料用量对片剂释放行为具有显著影响，当三者分别为20 目、14％和25％时，所制备的双相释放双层片能达到设计的释放目标，即3 min、 2 h、6 h 与12 h 的累积释放率应分别为标示量的20％～ 25％、50％～ 55％、65％～ 75％和90％以上。

Based on the concept of Quality by Design (QBD), a parameter design interval was established for critical quality attributes (CQAs) affecting nefopam hydrochloride biphase-release bilayer tablets, and the risk assessment and screening of each key process parameter (CPP) were carried out using failure mode and impact analysis (FMEA) and Plackett-Burman design (PBD). Box-Behnken design (BBD) was used to further optimize CPPs, determine the control strategy of design space and establish statistical models. Minitab and Design-Expert softwares were used as experimental design and data analysis tools to analyze the preparation process of nefopam hydrochloride biphase-release bilayer tablets. The results showed that the optimized formulation parameters were as follows: particle size was 21.79 mesh (the actual value was 20 mesh), the dosage of release regulator was 14.06％ (the actual value was 14％) and the dosage of sustained-release material was 25％. Under these conditions, the dissolution amounts of selfmade biphase-release bilayer tablets at 3 min, 2 h, 6 h and 12 h were respectively 20％ - 25％, 50％ - 55％, 65％ - 75％ and above 90％, which met the quality target product profiles (QTPPs).