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

ABSTRACT

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 effective information on the spectrum, the influence of resolution on PLSR models performance, the variance contribution/cumulative variance contribution of PLSR model principal components (PCs), the relation of PCI loadings, scores of the spectra and CFZ/Mono-CFZ content, and the mechanism of quantitative analysis was in-depth explained simultaneously. Eventually the most suitable PLSR models in 0.0000-10.0000 % w/w % obtained. That can provide theoretical support for quantitative analysis of low-content impurity crystal during the production, storage and transportation of CFZ tablets, thus provide reference methods for quality control of CFZ tablets and a reliable reference method for quantitative analysis of impurity crystal forms and quality control of similar drugs.