AN INVESTIGATION OF INTERACTIONS BETWEEN NIFEDIPINE AND POLYMER IN SOLID DISPERSION USING RAMAN SPECTROSCOPY

Abstract

Drug-polymer interaction or their miscibility has been known to be a key factor to impede recrystallization of drug dispersed in a polymeric matrix of solid dispersion. The purpose of this study was to demonstrate the feasibility of Raman spectroscopy to determine the extent of drug-polymer interaction in solid dispersions and to investigate whether the present interaction could stabilize the solid state morphology of the drug substance. The solid dispersions of nifedipine and polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer (Soluplus®) with drug loadings of 10, 30, 50, 70 and 90% w/w were prepared by freeze drying, melting and solvent evaporation. The miscibility of solid dispersions was characterized by X-ray powder diffractometry, differential scanning calorimetry, Fourier transform-infrared spectroscopy (FT-IR), solid state-nuclear magnetic resonance spectroscopy (ss-NMR) and Raman spectroscopy. The extent of drug-polymer interaction in X-ray amorphous samples were determined by utilizing Gaussian function fitting of Raman spectra obtained. The results demonstrated that the drug and polymer interacted via hydrogen bonding as indicated by FT-IR and ss-NMR and hydrophobic interaction identified by Raman spectroscopy. The extent of drug-polymer interaction and miscibility levels were found to be more dependent on the amounts of drug loading than preparation methods. The amount of 30% w/w drug loading was shown to be a saturated concentration for the miscibility of nifedipine in the polymer. Crystallization and amorphous phase separation were delayed in the miscible mixtures. When the drug loading was much lower than the saturated concentration, the strength of drug-polymer interaction effectively inhibited the amorphous phase separation. Therefore, Raman spectroscopy could be applied to investigate the extent of hydrophobic interaction in the solid dispersion of drug and polymer both qualitatively and quantitatively.