MONITORING CRYSTAL TRANSFORMATIONS OF THE POLYMORPHIC FORMS OF NIMODIPINE

RUBEN M. MAGGIO; NAIRA M. BALZARETI; NATALIA L. CALVO; TEODORO S. KAUFMAN

Rosario

Congreso; 4th International Meeting on Pharmaceutical Sciences; 2016

Universidad nacional de Rosario y Universidad nacional de Cordoba

The term structural (crystal) polymorphism refers to the ability of a substance to exist as two or more crystalline phases that have different arrangements in their crystal lattice. The polymorphs may differ in their physical and chemical properties; this could affect in their pharmaceutical processing or the performance of formulated products.Nimodipine (NIM) is a calcium channel blocker, which has two polymorphic forms (MI and MII). MI doubles the aqueous solubility of MII (at 25 and 37ºC); hence, dosage forms should contain only MI. Therefore, we developed a dynamic thermal approach based on chemometrics and ATR-FTIR (Attenuated Total Reflectance - Fourier Transform Infrared Spectroscopy) to monitor thermally induced changes suffered by the crystalline forms of NIM, as a quality control tool.The crystalline forms of NIM were prepared and characterized (Raman, FTIR, differential scanning calorimetry, scanning electron microscopy and X-ray powder diffraction). For analysis, samples were heated (30-148ºC), and the periodically acquired spectra were arranged matrix-wise (temperature/wavenumber). The spectral data were processed by principal component analysis and multivariate curve resolution to determine number of species, their pure spectra and concentration profiles. The spectra were used to establish the identity of each involved species, whilst the concentration profiles were used to determine polymorph interconversions and transition temperatures. The MII profile revealed two transformations: first to MI; then fusion, crystallizing as an amorphous solid, without spectral changes. Conversely, MI only displayed a fusion. Analyzed bulk-drug commercial samples exhibited two transitions, like MII, at slightly lower temperatures. This phenomenon was probably due to the presence of MII/MI mixtures, as confirmed by the concertation profiles and analysis of a synthetic sample of MII/MI (1:1), which exhibited the same behavior.In conclusion, the proposed dynamic thermal ATR-FTIR/chemometrics method enabled identification of NIM crystal forms and monitoring their interconversion.