Optimization of Linagliptin and Valsartan Bilayer Tablets Using Quality by Design

Indian Journal of Pharmaceutical Education and Research

  • Dong Hyeok Kim1Department of Pharmacy, Kyungsung University, Busan, REPUBLIC OF KOREA., 2Brain Busan Plus 21 Research Project Group, Department of Pharmacy Kyungsung University, 309 Busan, REPUBLIC OF KOREA.
  • Chul Yong Bae3Department of Applied Pharmacy, Major in Pharmaceutical Industry, College of Pharmacy, Chungbuk National University, Cheongju, REPUBLIC OF KOREA.
  • Shugeng Cao4Daniel K. Inouye College of Pharmacy, University of Hawai’i at Hilo, Hawaii, UNITED STATES OF AMERICA.
  • Jae Sung Pyo1Department of Pharmacy, Kyungsung University, Busan, REPUBLIC OF KOREA., 2Brain Busan Plus 21 Research Project Group, Department of Pharmacy Kyungsung University, 309 Busan, REPUBLIC OF KOREA.
  • Yeun Hee Kim5Formulation team, Daejeon Research Institute, Kolon Pharm, Daejeon, REPUBLIC OF KOREA.
  • Kang Min Kim6Department of Pharmaceutical Science and Technology, Kyungsung University, Busan, REPUBLIC OF KOREA.

Volume 60 Issue 3s Pages s1046-s1055

DOI: 10.5530/ijper.20264282

Abstract

Background and Objectives: The development of a bilayer tablet containing valsartan and linagliptin requires precise control of formulation and process variables to ensure consistent product quality. This study aimed to establish the design space of the bilayer tablet by applying a Quality by Design (QbD) approach, thereby optimizing key formulation and process parameters to meet predefined Critical Quality Attributes (CQAs). Materials and Methods: A 23+3 full-factorial Design of Experiments (DoE) was implemented to investigate the effects of formulation factors, including microcrystalline cellulose and crospovidone and the process parameter, main compression force. CQAs, including hardness, friability, disintegration time, assay, content uniformity, and dissolution rate, were evaluated using Design Expert software. Statistical analysis was performed through Analysis of Variance (ANOVA) to identify significant factors influencing each CQA. Results: ANOVA results indicated that the main compression force significantly affected tablet hardness, friability, disintegration time, and dissolution rate (p<0.05). Additionally, microcrystalline cellulose and crospovidone showed a significant impact on disintegration time of valsartan (p<0.05). The optimized formulation and process ranges that satisfied all CQAs were determined as follows: microcrystalline cellulose (7-40%), crospovidone (4-13%), and main compression force (1070-1570 kgf). Conclusion: Through the QbD-based DoE study, the optimal design space for the bilayer tablet of linagliptin and valsartan was successfully established. The findings demonstrate that systematic formulation and process optimization can effectively ensure the desired product quality and performance.

Keywords

  • Bilayer Tablet
  • Design of Experiment
  • Linagliptin
  • Quality by Design
  • Valsartan
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