Artículo
Chemometrics-assisted study of the interconversion between the crystalline forms of nimodipine
Calvo, Natalia Lorena
; Balzaretti, Vilma Teresa; Antonio, Marina
; Kaufman, Teodoro Saul
; Maggio, Ruben Mariano
Fecha de publicación:
09/2018
Editorial:
Elsevier Science
Revista:
Journal of Pharmaceutical and Biomedical Analysis
ISSN:
0731-7085
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Nimodipine (NIM) is a calcium channel-blocking agent, which in the solid state exhibits two crystalline modifications, Mode I and Mode II. The first one is a racemic mixture, while the second is a conglomerate. Because the drug has poor aqueous solubility and Mode I is twice as soluble as Mode II, the former is widely preferred for the development of pharmaceutical forms. In order to study the effect of thermal stimuli on the behavior of NIM, an analytical method was developed coupling ATR-FTIR spectroscopy to Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS). The method allowed to monitor the transformations of each polymorph, their respective mixtures and commercial samples, during the thermal treatment. It was observed that Mode II experienced changes during the experiments and the chemometric technique provided the abundance profile and the pure spectra of the different species involved. In this way, it was established that Mode II has two transitions, at 116.8 °C and 131.9 °C, which reflect that Mode II is first transformed into Mode I, which then melts. The liquid phase solidifies to give an amorphous (AM) vitreous solid, which does not revert to the crystalline state. The analysis of a commercial sample of NIM exhibited the similar transformations than Mode II; however, a pronounced decrease was noted in the first transition temperature (95 °C), whereas the second remained essentially unchanged (131.6 °C). This could be a result of the presence of mixtures of Mode I and Mode II (0.32:0.68) in the bulk solid, as confirmed by the analysis of a physical mixture of crystals of Modes I and II. Therefore, it was concluded that the developed ATR-FTIR/MCR-ALS method is suitable for the detailed analysis of the crystalline forms of NIM in bulk drug and enables de study of their possible thermally promoted interconversions.
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Articulos(IQUIR)
Articulos de INST.DE QUIMICA ROSARIO
Articulos de INST.DE QUIMICA ROSARIO
Citación
Calvo, Natalia Lorena; Balzaretti, Vilma Teresa; Antonio, Marina; Kaufman, Teodoro Saul; Maggio, Ruben Mariano; Chemometrics-assisted study of the interconversion between the crystalline forms of nimodipine; Elsevier Science; Journal of Pharmaceutical and Biomedical Analysis; 158; 9-2018; 461-470
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