Co-amorphous technology was recently introduced to stabilize drugs in the amorphous state for drug development. We examined the predictability of the formation of co-amorphous systems and identified two reliable indicators of successful formation: (1) a negative Δ Hmix value and (2) small Δlog P between components. Moreover, we found that the stability of co-amorphous systems was improved when (1) Δ Hmix was negative and (2) amorphous forms of the constituent compounds were stable. Furthermore, we concluded that co-amorphous systems with small (negatively large) Δ Hmix values had lower hygroscopicity. Typically, amorphous solid dispersions exhibit hygroscopicity because polymers exhibit large hygroscopicity. We proved the superiority of co-amorphous technology over amorphous solid dispersion in this respect. Our results provide methods for (1) establishing a screening method and (2) improving hygroscopicity, which may make co-amorphous technology more useful than amorphous solid dispersion technology.
Keywords: co-amorphous; hydrogen bonds; hygroscopicity; lipophilicity; mixing enthalpy; physical stability; screening.