This study investigated thiamine degradation in thiamine mononitrate (TMN):polymer solid dispersions, accounting for the physical state of the vitamin and the recrystallization tendency of TMN in these dispersions. Results were compared with those from solid dispersions containing a different salt form of thiamine (thiamine chloride hydrochloride (TClHCl)). TMN:polymer dispersions were prepared by lyophilizing solutions containing TMN and amorphous polymers (pectin and PVP (polyvinylpyrrolidone)). Samples were stored in controlled temperature and relative humidity (RH) environments for eight weeks and monitored periodically by X-ray diffraction and high performance liquid chromatography (HPLC). Moisture sorption, glass transition temperature (Tg), intermolecular interactions, and pH were also determined. Similar to the TClHCl:polymer dispersions, thiamine was more chemically labile in the amorphous state than the crystalline state, when present in lower proportions in amorphous TMN:polymer dispersions despite increasing Tg values, when environmental storage conditions exceeded the Tg of the dispersion, and when co-formulated with PVP compared to pectin. When thiamine remained as an amorphous solid, chemical stability of thiamine did not differ as a function of counterion present (TMN vs. TClHCl). However, storage at 75% RH led to hydration of thiamine:PVP dispersions, and the resulting pH of the solutions as a function of thiamine salt form led to a higher chemical stability in the acidic TClHCl samples than in the neutral TMN samples.
Keywords: amorphous solid dispersion; amorphous stability; chemical stability; physical stability; thiamine; thiamine degradation; thiamine mononitrate; vitamin B1.