Design and Optimization of the Formulation and Technology of Theophylline Gel Matrix Sustained-release Tablets Based on QbD Concept
- VernacularTitle:基于QbD理念的茶碱凝胶骨架缓释片处方工艺设计与优化
- Author:
Xiwei JIANG
1
;
Yunyang FEI
1
;
Guiyu LIAN
1
;
Rongwu XIANG
1
;
Fei ZHAI
1
;
Yukun JIANG
1
;
Xin CHE
1
Author Information
1. College of Pharmacy，Shenyang Pharmaceutical University，Shenyang 110016，China
- Publication Type:Journal Article
- Keywords:
Theophylline;
Hydrophilic gel matrix sustained-release tablets;
Quality by design;
Critical quality attributes;
Critical process parameters;
Orthogonal test;
Design space;
Formulation;
Technology;
Optimization
- From:
China Pharmacy
2019;30(18):2502-2507
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To design and optimize the formulation and technology of Theophylline hydrophilic gel matrix sustained-release tablets （self-made sustained-release tablets for short） based on the concept of “Quality by Design” （QbD）. METHODS： Diluent type， tablet diameter， the property of adhesive （ratio of different adhesive types）， the amount of adhesive were regarded as critical process parameters （CPPs）. Similarity factor of dissolution curves of self-made Theophylline sustained-release tablets and reference preparation and its accumulative release rate at different time points were regarded as critical quality attributes （CQAs）. L18（34） orthogonal tablet was adopted for design and trial， and secondary polynomial regression model was established. By using Modde 12.0 software， the design space and its acceptable range （PAR） were calculated through the optimal model. The optimal formulation and technology of Theophylline sustained-release tablets was determined， and validation test and Monte Carlo simulation verification were conducted. RESULTS： The optimal model with good coincidence， accuracy， validity and reproducibility was obtained， which could better fit the relationship between CQAs and CPPs. The design space and PAR value were obtained by further calculation （The optimum value of diluent was lactose； tablet diameter was 9.07-9.33 mm， and the optimal value was 9.20 mm； ratio of HPMC K4M to HPMC was 0.50-0.83， and the optimal value was 0.80； total amount of HPMC was 0.036 0-0.041 3 g per tablet， and the optimal value was 0.038 g per tablet）. The optimal formulation and technology included that ratio of theophylline， HPMC K4M and HPMC K100M were 50％， 15.48％ and 3.87％， respectively； the rest was filled with lactose and the diameter of the tablet was 9.20 mm. The results of validation confirmed that self-made Theophylline sustained-release tablets had similar in vitro release behavior compared with reference preparation. CONCLUSIONS： Based on the concept of QbD， the formulation and technology of Theophylline sustained-release tablets can meet the requirements of design， and the CPPs can be adjusted within the PAR range to meet the requirements of CQAs. This shows that the QbD concept is scientific and effective in the design and optimization of the formulation and technology of sustained and controlled release preparations.
