In-line monitoring of cocrystallization process and quantification of carbamazepine-nicotinamide cocrystal using Raman spectroscopy and chemometric tools

Autor(es)

Soares, Frederico L. F. ; Carneiro, Renato L.

• Tipo de documento: Artigo Científico
• Fonte: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY; v. 180, p. 1-8, JUN 5 2017.
• Citações Web of Science: 9

Resumo

A cocrystallization process may involve several molecular species, which are generally solid under ambient conditions. Thus, accurate monitoring of different components that might appear during the reaction is necessary, as well as quantification of the final product. This work reports for the first time the synthesis of carbamazepine-nicotinamide cocrystal in aqueous media with a full conversion. The reactions were monitored by Raman spectroscopy coupled with Multivariate Curve Resolution - Alternating Least Squares, and the quantification of the final product among its coformers was performed using Raman spectroscopy and Partial Least Squares regression. The slurry reaction was made in four different conditions: room temperature, 40 degrees C, 60 degrees C and 80 degrees C. The slurry reaction at 80 degrees C enabled a full conversion of initial substrates into the cocrystal form, using water as solvent for a greener method. The employment of MCR-ALS coupled with Raman spectroscopy enabled to observe the main steps of the reactions, such as drug dissolution, nucleation and crystallization of the cocrystal. The PLS models gave mean errors of cross validation around 2.0 (% wt/wt), and errors of validation between 2.5 and 8.2 (% wt/wt) for all components. These were good results since the spectra of cocrystals and the physical mixture of the coformers present some similar peaks. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 10/16520-5 - Aplicação de métodos quimiométricos de calibração e resolução multivariada de curvas em espectroscopia Raman para análise qualitativa, quantitativa e de polimorfismo em fármacos
• Beneficiário: Renato Lajarim Carneiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular