CLASSIFICATION OF FLUCONAZOLE API POLYMORPHIC FORMS IN PHARMACEUTICAL PRODUCTS BY ASSOCIATING FTIR, NIR AND RAMAN TO PLS-DA

The main goal of this work was to prove the ability of the combination between vibrational spectroscopy techniques and PLS-DA to differentiate between different polymorphic forms of fluconazole in pharmaceutical products. These are mostly manufactured based on fluconazole polymorphic form- II and form- III. These crystalline forms may undergo polymorphic transition during the manufacturing or storage conditions process. Therefore, it is important to confirm if the expected polymorphic form is still present or not.

FT-IR, FT-NIR and Raman spectroscopies were associated to PLS-DA and used to build robust classification models to distinguish between form- II, Form- III and monohydrate form. Based on the results, it is shown that PLS-DA models have a high efficiency to classify various fluconazole polymorphs, with a high sensitivity and specificity. Finally, the selectivity of the PLS-DA models is proven based on the analysis of two samples of itraconazole and miconazole that belong to the same antifungal class as fluconazole. These two samples mimic potential contaminants. Based on the plots of Hotelling T² vs Q residuals, miconazole and itraconazole are significantly considered outliers and rejected.