Quantitative analysis of low-content impurity crystal forms in canagliflozin tablets by NIR solid-state analysis technique

Different contents (0.0000 %–10.0000 % w/w %) of CFZ or Mono-CFZ in simulated CFZ tablets were quantified by Near-Infrared (NIR) solid-state analytical technique (different resolutions and different wavenumber regions) combined with stoichiometry. Different pretreatment methods pretreated the original data, which were used to establish PLSR calibration curves to quantify CFZ or Mono-CFZ content. And the PCs loadings and scores of PLSR models used to explain the information of NIR spectrum. [Display omitted] •Different contents of CFZ or Mono-CFZ in simulated CFZ tablets were quantified by Near-Infrared (NIR) solid-state analytical technique combined with stoichiometry.•Data at different resolutions with different wavenumber regions of NIR, which pretreated by different pretreatment methods, were selected to establish the PLSR calibration curves for quantify the content of CFZ or Mono-CFZ.•The PCs loadings and scores of PLSR models used to explain the information of NIR spectrum. Canagliflozin (CFZ) tablets was a commercially new class of anti-diabetic drug, CFZ had various anhydrate crystal forms and two hydrate crystal forms (Canagliflozin hemihydrate (Hemi-CFZ) and Canagliflozin monohydrate (Mono-CFZ) crystal form). The active pharmaceutical ingredients (APIs) of commercially available CFZ tablets were Hemi-CFZ, was easily convert to CFZ or Mono-CFZ under the influence of temperature, pressure, humidity and other factors in tablets processing, storage, and transportation, thus affected bioavailability and efficacy of tablets. Therefore, quantitative analysis of low-content CFZ and Mono-CFZ in tablets was essential to control tablets’ quality. The main objective of this study was to explore the feasibility and in-depth explain its quantitative analysis mechanism of NIR for quantitative analysis of low-content CFZ/Mono-CFZ in CFZ tablets. PLSR models for low-content CFZ/Mono-CFZ were established by NIR solid-state analysis technique in different resolutions with different wavenumber regions combined with various pretreatments methods (such as Multiplicative Scatter Correction (MSC), Standard Normal Variate (SNV), Savitzky-Golay First Derivative (SG1st), Savitzky-Golay Second Derivative (SG2nd) and Wavelet Transform (WT)), and the PLSR models were verified. The feasibility of NIR spectroscopy for quantitative analysis of low-content CFZ and Mono-CFZ in CFZ tablets was discussed and analyzed from multiple perspectives, which included the distribution of effe