CONICET | Buscador de Institutos y Recursos Humanos

Crystal polymorphism represents the ability of a substance to exist as two or more crystalline phases, having different arrangements and molecular conformations in the crystal lattice. This phenomenon is currently a crucial problem for the pharmaceutical industry. Albendazole (ABZ) is an anthelmintic benzimidazole derivative with a broad spectrum of activity. Aiming to develop a quantitative method for the determination of ABZ form I (commercial) in ABZ samples, crystalline forms I and II of ABZ were prepared and characterized according to the literature. A series of 42 mixtures containing both polymorphs was prepared according to an experimental design, by mechanical mixing. These were divided into calibration set (18 samples), validation set I (15 samples) and validation set II (9 samples). These were analyzed in triplicate by Raman Microscopy (126 spectra). In order to predict the abundance of the polymorphs in the samples, a PLS multivariate calibration model was built and validated. The optimum conditions for the calibration set were obtained by cross-validation in the 1286-1402 cm-1 spectral region, employing 3 significant latent variables; no sample pre-treatment were required. The method performance was evaluated by analysis of the validation sets, examining the level of recovery and dispersion, statistics and figures of merit. The accuracy was evaluated at 3 concentration levels by calculating the analyte recoveries in the validation set II. Method precision was assessed by calculating data dispersion at different levels. These preliminary results suggest that the combination of Raman spectroscopy with multivariate analysis is potentially applicable to the analysis of crystal polymorphism in this active pharmaceutical ingredient.