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

Abstract

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 properties 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 characterized by spectroscopic [solid-state nuclear magnetic resonance and near infrared (NIR)] and diffractometric (powder X-ray diffraction) methods. Then, the NIR and attenuated total reflectance-mid infrared (ATR-MIR) spectra of both forms were conveniently 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 validation (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 characteristics, 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.