Chemometrics-Assisted Study of the Interconversion between the Crystalline Forms of Nimodipine

CALVO, NATALIA L.; BALZARETTI, N. M.; ANTONIO, M.; KAUFMAN, T. S.; MAGGIO, R. M.

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018 vol. 158 p. 461 - 470

0731-7085

Nimodipine(NIM) is a calcium channel-blocking agent, which in the solid state exhibitstwo crystalline modifications, Mode I and Mode II. The first one is a racemicmixture, while the second is a conglomerate. Because the drug has poor aqueoussolubility and Mode I is twice as soluble as Mode II, the former is widelypreferred for the development of pharmaceutical forms. In order to study theeffect of thermal stimuli on the behavior of NIM, an analytical method wasdeveloped coupling ATR-FTIR spectroscopy to Multivariate Curve Resolution withAlternating Least Squares (MCR-ALS). The method allowed to monitor the transformations of eachpolymorph, their respective mixtures and commercial samples, during the thermaltreatment.Itwas observed that Mode II experienced changes during the experiments and thechemometric technique provided the abundance profile and the pure spectra ofthe different species involved. In this way, it was established that Mode IIhas two transitions, at 116.8ºC and 131.9ºC, which reflect that Mode II isfirst transformed into Mode I, which then melts. The liquid phase solidifies togive an amorphous (AM) vitreous solid, which does not revert to the crystallinestate. The analysis of a commercial sample of NIM exhibited the similar transformationsthan Mode II; however, a pronounced decrease was noted in the first transitiontemperature (95ºC), whereas the second remained essentially unchanged (131.6ºC).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 physicalmixture of crystals of Modes I and II. Therefore, it was concluded that the developed ATR-FTIR/MCR-ALSmethod is suitable for the detailed analysis of the crystalline forms of NIM inbulk drug and enables de study of their possible thermally promoted interconversions.