Determinación de dos polimorfos de albendazol usando Raman y análisis multivariante

CALVO N.; MAGGIO R.; ARIAS, JUAN MARCELO; BEN ALTABEF, AIDA; KAUFMAN T.

Cordoba

Congreso; 3º Reunión Internacional de Ciencias Farmacéuticas; 2014

Universidad Nacional de Cordoba

DETERMINATION OF ALBENDAZOLE POLYMORPHS USING RAMANSPECTROSCOPY COUPLED TO MULTIVARIATE ANALYSISCalvo N.a, Maggio R.a, Arias J.b, Ben Altabef A.b, Kaufman T.acalvo@iquir-conicet.gov.araÁrea de Análisis de Medicamentos, Facultad de Ciencias Bioquímicas y Farmacéuticas, UniversidadNacional de Rosario e Instituto de Química Rosario (IQUIR, CONICET-UNR),Suipacha 531, Rosario S2002LRK, ArgentinabInstituto de Química Física, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional deTucumán (INQUINOA, CONICET-UNT), San Lorenzo 456, Tucumán T4000CAN, Argentina.Keywords: Albendazole, Polymorphism, Raman/PLS determinationCrystal polymorphism, a crucial problem for the pharmaceutical industry, represents theability of a substance to exist as two or more crystalline phases, having differentarrangements and molecular conformations in the crystal lattice.1Albendazole (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 particularattention to possible undesired phase changes during both manufacturing process andstorage as pharmaceutical formulation. Aiming to develop a method for the determinationof ABZ form I in ABZ raw material, both polymorphs were prepared and characterized.2A set of 42 mixtures containing both polymorphs was prepared by mechanical mixing, anddivided in three sets: calibration (18 samples), validation I (15 samples) and validation II (9samples). These were analyzed in triplicate by Raman Microscopy (126 spectra).To predict the abundance of the polymorphs in the samples, a Partial Least Squarescalibration model was built and validated. The optimum conditions were obtained by crossvalidationin 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 therecovery levels, dispersion, statistics (r2=0.8801) and figures of merit (LOD=1.8%). Theaccuracy was evaluated at 3 concentration levels by calculating the analyte recoveries in thevalidation set II (recovery=101.4%). Method precision was assessed by calculating datadispersion at different levels (SD=20%).These preliminary results suggest that the combination of Raman spectroscopy withmultivariate analysis is potentially applicable to the analysis of crystal polymorphism inthis active pharmaceutical ingredient.1 Brittain, H. G. (Ed.), (1999). Polymorphism in Pharmaceutical Solids. Dekker, NY, pp.1?31.2 Pranzo M. B., Cruickshank D., Coruzzi M., Caira M. R., Bettini R. (2010),Enantiotropically related albendazole polymorphs, J Pharm Sci. 99(9): 3731-42.