Stability of Paracetamol Amorphized by Co-Melting with Various Cellulose Derivatives

Abstract

Co-melting paracetamol with different cellulose derivatives leads to full or partial amorphization of active substance. The aim of this study was to determine whether the amorphization of paracetamol after co-melting with cellulose derivatives is stable and whether it depends on the type of cellulose derivative added and the ratio of components. Mixtures of paracetamol with cellulose derivatives containing different proportions of components were prepared. Using differential scanning calorimetry (DSC), the samples were melted and the amorphization of paracetamol was confirmed. After 2 and 4 months, the samples were reanalyzed to determine the amorphization stability during storage and the difference in the effect of different polymers on the amorphization stability. The physical mixtures were additionally tested using Fourier transform infrared (FTIR) and Raman spectroscopic methods to confirm that no solid-phase interactions were noticed. Samples were also analyzed using ultrahigh-performance liquid chromatography (UHPLC) to assess the effect of co-melting and storage on the chemical stability of paracetamol. The results show that paracetamol amorphizes after co-melting with cellulose derivatives. The crystallization of paracetamol after co-melting depends on the polymer used and the proportions of the components. No interactions between the components and the chemical stability of paracetamol in the tested samples were confirmed.