DETERMINATION OF ALBENDAZOLE POLYMORPHS USING RAMAN SPECTROSCOPY COUPLED TO MULTIVARIATE ANALYSIS

CALVO N. ; MAGGIO R.; ARIAS J. ; BEN ALTABEF A. ; KAUFMAN T.

Córdoba

Congreso; RICIFA2014; 2014

Crystal polymorphism, a crucial problem for th e 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. 1 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 chan ges 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. 2 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 cross- validation in the 1402-1286- cm -1 spectral region, employing 3 significant latent variables, without sample pre-treatment. Crystal polymorphism, a crucial problem for th e 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. 1 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 chan ges 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. 2 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 cross- validation in the 1402-1286- cm -1 spectral region, employing 3 significant latent variables, without sample pre-treatment.