Quantitative analysis of low-content impurity crystal forms in canagliflozin tablets by NIR solid-state analysis
Mingdi Liu1, Jichao Liu2, Qiuhong Wang2
1College of Chemistry and Chemical Engineering, Qinghai Minzu University, Xining 810007, PR China; State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Key Laboratory of Resource Chemistry and Eco-environmental Protection in Tibetan Plateau, State Ethnic Affairs Commission, Xining 810007, PR China.
This study demonstrates Near-Infrared (NIR) spectroscopy effectively quantifies low-content Canagliflozin (CFZ) and Canagliflozin monohydrate (Mono-CFZ) impurities in CFZ tablets. This method ensures drug quality by analyzing crystal form changes during production and storage.
Area of Science:
- Pharmaceutical Science
- Analytical Chemistry
- Spectroscopy
Background:
- Canagliflozin (CFZ) tablets contain Canagliflozin hemihydrate (Hemi-CFZ) as the active pharmaceutical ingredient.
- Hemi-CFZ can transform into other crystal forms (CFZ, Mono-CFZ) due to processing, storage, and transport conditions.
- These transformations can impact CFZ tablet bioavailability and efficacy, necessitating precise quality control.
Purpose of the Study:
- To explore the feasibility of Near-Infrared (NIR) spectroscopy for quantitative analysis of low-content CFZ and Mono-CFZ in CFZ tablets.
- To elucidate the underlying quantitative analysis mechanism of NIR for these impurities.
- To establish reliable methods for quality control of CFZ tablets.
Main Methods:
- Utilized NIR solid-state analysis combined with various spectral pretreatments (MSC, SNV, SG, WT).
- Developed and validated Partial Least Squares Regression (PLSR) models at different resolutions and wavenumber regions.
- Analyzed spectral information distribution, resolution influence, principal component contributions, and loadings-scores relationships.
Main Results:
- Established optimal PLSR models for quantifying low-content CFZ and Mono-CFZ (0.0000-10.0000% w/w).
- Demonstrated the feasibility and explained the mechanism of NIR spectroscopy for impurity analysis.
- Validated the effectiveness of different pretreatment methods and spectral resolutions.
Conclusions:
- NIR spectroscopy is a feasible and effective technique for quantitative analysis of low-content CFZ and Mono-CFZ impurities in CFZ tablets.
- The study provides theoretical support for quality control during CFZ tablet production, storage, and transportation.
- Offers a reliable reference method for analyzing impurity crystal forms in similar pharmaceutical products.
