Form quantitation in desmotropic mixtures of albendazole bulk drug by chemometrics-assisted analysis of vibrational spectra

Albendazole is a benzimidazole-type active pharmaceutical ingredient, and one of the most effective broad-spectrum anthelminthic agents. The drug has two solid-state forms (ALB I and ALB II) which are desmotropes; both of them seem to be currently marketed. However, using the wrong crystalline solid form for formulation may have an undesired impact on the physicochemical and/or bioavailability prop-erties of the drug product. In order to develop new, simple, and less expensive alternatives toward the determination of the level of albendazole ALB I in its mixtures with ALB II, both desmotropes were prepared, and properly charac-terized by spectroscopic [solid-state nuclear magnetic resonance and near infrared (NIR)] and diffracto-metric (powder X-ray diffraction) methods. Then, the NIR and attenuated total reflectance-mid infrared (ATR-MIR) spectra of both forms were con-veniently pre-treated and employed for the development and optimization of partial least squares (PLS)-potentiated quantification models (NIR/PLS and ATR-MIR/PLS). The latter were also subjected to valida-tion (accuracy, precision, limits of detection and quantification, etc.) and further used to assess the level of the unwanted ALB II form in the bulk drug. The NIR/PLS method displayed the most satisfactory char-acteristics, including a limit of quantitation interval of 3.6 +/- 1 %w/w; it outperformed both, the ATR-MIR/ PLS counterpart (limit of quantitation interval of 14.0 +/- 3.4 %w/w) and a previously published and more demanding Raman/PLS alternative. (c) 2021 Elsevier B.V. All rights reserved.