基于QbD理念的肿节风分散片制备工艺的优化

基于质量源于设计(QbD)理念,应用鱼骨图、失效模型与影响分析模型筛选了可能影响分散片质量的风险因素。继而采用Plackett-Burman设计,以片剂的分散均匀性(崩解时间)、花斑率及颗粒成型性为评价指标筛选有显著性影响的处方因素,再运用中心点复合设计-响应面法优化肿节风分散片的处方配比,建立工艺设计空间并进行验证。结果显示,崩解剂用量、润滑剂用量及黏合剂用量因素是影响试验结果的3个关键处方因素,所得优化处方为:崩解剂(交联聚乙烯吡咯烷酮)用量占处方量15.5%,润滑剂(硬脂酸镁)占处方量的0.4%,黏合剂(85%乙醇)用量为干浸膏粉2.5倍量,按此处方制备肿节风分散片,崩解时间小于45 s,花斑率低于10%。本试验表明,基于QbD理念对肿节风分散片的处方进行优化是可行的,设计空间范围内制备的分散片符合要求且外观较好,可为其大生产提供参考。

Optimization of Preparation Process of Glabrous Sarcandra Herb Dispersible Tablets Based on Quality by Design Concept

Based on the concept of quality by design(QbD), the risk factors which affected the critical quality attributes of dispersible tablets of Glabrous Sarcandra Herb were analyzed by fishbone diagram analysis, failure mode and effects analysis(FMEA). Plackett-Burman experimental design was used to screen the formulation factors which had significant influences on the evaluation indexes, namely dispersible uniformity(disintegration time), speckle rate and particle formability. According to the experimental results, disintegrant dosage, lubricant dosage and adhesive dosage were confirmed to be the critical process parameters. Then, these formulation factors were further investigated by central composite design combined with response surface methodology. On the basis of the 3 D response surface plots, the design space was established and verified. The optimal formulation was composed of 15.5% of cross-linked polyvinyl pyrrolidone(PVPP) as disintegrant, 0.4% of magnesium stearate as lubricant and 85% ethanol as adhesive with amount of 2.5 times as much as that of dry extract powder. The disintegration time of the optimal dispersible tablets was less than 45 s, and the speckle rate was less than 10%. These results indicated that it was feasible to optimize the formulation and preparation of Glabrous Sarcandra Herb dispersible tablets based on the concept and method of QbD. The dispersible tablets prepared with the parameters in the design space had good appearances and suitable disintegration profiles, which could provide references for industrial production.