DETERMINATION OF ALBENDAZOLE POLYMORPHS USING RAMAN SPECTROSCOPY COUPLED TO MULTIVARIATE ANALYSIS

NATALIA L. CALVO; RUBÉN M. MAGGIO; TEODORO S. KAUFMAN

Cordoba

Congreso; RICiFa 2014; 2014

Comite organizador

Crystal polymorphism, a crucial problem for the pharmaceutical industry, represents the ability of a substance to exist as two or more crystalline phases, having different arrangements and molecular conformations in the crystal lattice. Albendazole (ABZ) is a broad spectrum antihelmintic, which presents two polymorphs (Forms I and II). The form II is metastable, therefore it is necessary to pay particular attention to possible undesired phase changes during both manufacturing process and storage as pharmaceutical formulation. Aiming to develop a method for the determination of ABZ form I in ABZ raw material, both polymorphs were prepared and characterized. A set of 42 mixtures containing both polymorphs was prepared by mechanical mixing, and divided in three sets: calibration (18 samples), validation I (15 samples) and validation II (9 samples). These were analyzed in triplicate by Raman Microscopy (126 spectra). To predict the abundance of the polymorphs in the samples, a Partial Least Squares calibration model was built and validated. The optimum conditions were obtained by crossvalidation in the 1402-1286 cm-1 spectral region, employing 3 significant latent variables, without sample pre-treatment. Method performance was also evaluated by analysis of the validation sets, examining the recovery levels, dispersion, statistics (r^2=0.8801) and figures of merit (LOD=1.8%). The accuracy was evaluated at 3 concentration levels by calculating the analyte recoveries in the validation set II (recovery=101.4%). Method precision was assessed by calculating data dispersion at different levels (SD=20%). 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.