Investigation of physical properties and stability of indomethacin–cimetidine and naproxen–cimetidine co-amorphous systems prepared by quench cooling, coprecipitation and ball milling

Abstract

Abstract Objectives The objective was to characterize the structural behaviour of indomethacin–cimetidine and naproxen–cimetidine co-amorphous systems (1 : 1 molar ratio) prepared by quench cooling, co-evaporation and ball milling. Methods Powder X-ray diffraction (PXRD) and DSC were used to characterise the samples. Structural relaxation (i.e. molecular mobility) behaviour was obtained from the Kohlrausch–Williams–Watts (KWW) relationship. Key findings A glass transition temperature (Tg), on average 20 °C higher than the predicted Tg (calculated from the Fox equation), was observed in all samples. The structural relaxation was dependent on the preparative methods. At a storage temperature of 40 °C, a comparatively higher molecular mobility was observed in indomethacin–cimetidine samples prepared by ball milling (ln τβ = 0.8), while similar molecular mobility was found for the same sample prepared by quench cooling (ln τβ = 2.4) and co-evaporation (ln τβ = 2.5). In contrast, molecular mobility of the naproxen–cimetidine samples followed the order co-evaporation (ln τβ = 0.8), quench cooling (ln τβ = 1.6) and ball milling (ln τβ = 1.8). Conclusion The estimated relaxation times by the DSC-KWW method suggest that different preparative methods resulted in a variation of structural characteristics. Despite the differences in molecular mobility, all sample remained co-amorphous for up to 7 months.