摘要
目的基于质量源于设计(quality by design,QbD)理念设计优化缬沙坦双层片的制备工艺,并考察体外释放行为。方法运用鱼骨分析法结合风险评估,对影响双层片关键质量属性(CQAs)的各因素进行剖析,以综合评分Y3作为CQA,进行实验设计(DOE)。运用Plackett-Burman设计从缓释材料用量、缓释层速释层黏合剂用量、缓释层速释层制粒目数、速释层崩解剂用量、压片压力8个影响因素中筛选出关键工艺参数(CPPs)。结合Box-Behnken设计,对CPPs进行优化,建立设计空间,加以验证并考察其体外释药行为。结果缓释材料用量,缓释层制粒目数、速释层崩解剂用量3个CPPs对双层片释放行为影响较为显著,通过95%置信区间的优化,最终确定的CPPs范围为:缓释材料用量19%~23%、缓释层制粒目数20~26目、速释层崩解剂用量6%~8%,在此区间制备出的缬沙坦双层片符合设计要求,体外释药符合Ritger-Peppas方程。结论基于QbD理念设计的缬沙坦双层片制备工艺稳定可行,符合制剂设计的释放要求。
OBJECTIVE To optimize the preparation process of valsartan bilayer tablets and to investigate the in vitro release behavior.METHODS The fishbone analysis method combined with risk assessment was used to analyze the factors that affected the critical quality attributes(CQAs)of the bilayer tablets,and the comprehensive score Y3 was used as the CQA to carry out the design of experiments(DOE).The Plackett-Burman design was used to select the critical process parameters(CPPs)from the eight influencing factors of the dosage of sustained release material,the dosage of adhesive in the sustained release layer and the immediate release layer,the number of granulation meshes for the sustained release layer and the immediate release layer,the dosage of disintegrant in the immediate release layer,and the tableting pressure.In combination with the Box-Behnken design,optimized CPPs,established a design space,verified,and investigated its drug release behavior in vitro.RESULTS The three factors of sustained released materials,the number of granulated meshes of the sustained released layer and the dosage of disintegrant of the immediate released layer had a significant effect on the release behavior of the bilayer tablets.Through the optimization of the 95%confidence interval,the final CPPs range was as follows:the sustained release material dosage ranged from 19%to 23%,the sustained release layer granulation meshes ranged from 20 to 26,and immediate release layer disintegrating agent dosage ranged from 6%to 8%.The valsartan bilayer tablets prepared in this interval met the design requirements,and the in vitro drug release conformed to the Ritger-Peppas equation.CONCLUSION The preparation process of valsartan bilayer tablets designed based on the QbD concept is stable and feasible,and meets the release requirements of the formulation design.
作者
宁劲涛
孙敬蒙
汪卓明
张小雯
张炜煜
NING Jin-tao;SUN Jing-meng;WANG Zhuo-ming;ZHANG Xiao-wen;ZHANG Wei-yu(College of Pharmacy,Changchun University of Chinese Medicine,Changcun 130117,China;Department of Pharmacy,Bethune First Hospital,Jilin University,Changchun 130021,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2021年第3期210-217,共8页
Chinese Pharmaceutical Journal
基金
吉林省科技厅项目资助(20180311131YY)
吉林省教育科学“十三五”规划项目资助(GH19135)。
