Competition of thermodynamic and dynamic factors during formation of multicomponent particles via spray drying.

As psicose cannot be spray dried because of its low glass transition temperature (T(g)), additives have been used to manufacture spray-dried particles. Its thermodynamic miscibility with each additive was evaluated by thermal analysis and C solid-state nuclear magnetic resonance. Aspartame was miscible with psicose at all ratios, and spray-dried particles were obtained when T(g) of the mixture was higher than the outlet temperature of the spray dryer, where 30 wt % of psicose was loaded. poly(vinylpyrrolidone) and cluster dextrin were partially miscible with psicose, with a maximum loading of 40 wt %. When polymeric excipients were used, their mixing behavior with psicose was affected by the dynamic factor during the spray drying, that is, enhanced phase separation due to the molecular-weight difference. The T(g) value of the polymer-rich phases, which were likely to form shell layers on the surfaces, played an important role in determining availability of the spray-dried particles. Hydroxypropyl methylcellulose (HPMC) offered a very effective loading capacity of 80 wt %, due to distinct phase separation to form shell phase with a very high T(g). Because molecular weight of HPMC was the smallest among the polymeric excipients, the thermodynamic miscibility seemed to affect the dynamic phase separation. These results provide useful information for preparing multicomponent spray-dried particles.