Análise quantitativa de formas polimórficas do mebendazol no insumo farmacêutico ativo utilizando espectroscopias na região do infravermelho e terahertz

Abstract

Mebendazole (MBZ) is a broad spectrum anthelmintic drug, often used as therapy against parasites from intestinal lumen. This substance has three different polymorphic forms, A, B and C. Among these forms, form A has no anthelmintic effect and renders the medication totally inactive when it exceeds 30% of mebendazole content in the formulation. Form B shows higher toxicity when ingested orally. Therefore, form C is the pharmaceutically preferred one because it does not have the drawbacks of forms A and B, and is stable at room temperature. All polymorphic forms of MBZ have been reported in pharmaceutical raw materials and commercial formulae. Thus, the aim of this work is to quantify the polymorphic forms of mebendazole in raw material using mid infrared (MIR), near infrared (NIR) and terahertz (THz) spectroscopies. For this, we built a ternary mixture design with 21 samples of polymorphic forms of MBZ. Models based on regression by Partial Least Squares (PLS) were developed using preprocessed MIR, NIR and THz spectra. All these techniques were efficient in discriminating among polymorphic forms of the drug, which have different spectral profiles with changes in intensities of bands and peaks, and displacements thereof. The multivariate calibration PLS models showed satisfactory results in the quantification of polymorphic forms of MBZ in the raw material. The best results for each spectral region showed values of determination coefficient (R²) above 0.95, correlation coefficient (R) above 0.97 and average RMSEP of 0.0294 w/w, 0.0132 w/w and 0.0282 w/w to polymorphic forms A, B and C, respectively.