Design and In Vitro Release Study of Valsartan Bilayer Tablets Based on Quality by Design (QbD) Concept
NING Jin-tao1, SUN Jing-meng2, WANG Zhuo-ming1, ZHANG Xiao-wen1, ZHANG Wei-yu1*
1. College of Pharmacy,Changchun University of Chinese Medicine, Changcun 130117, China; 2. Department of Pharmacy, Bethune First Hospital, Jilin University, Changchun 130021, China
Abstract：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.
宁劲涛, 孙敬蒙, 汪卓明, 张小雯, 张炜煜. 基于QbD理念设计缬沙坦双层片及体外释放研究[J]. 中国药学杂志, 2021, 56(3): 210-217.
NING Jin-tao, SUN Jing-meng, WANG Zhuo-ming, ZHANG Xiao-wen, ZHANG Wei-yu. Design and In Vitro Release Study of Valsartan Bilayer Tablets Based on Quality by Design (QbD) Concept. Chinese Pharmaceutical Journal, 2021, 56(3): 210-217.
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2021, Vol. 56 
