  Much work has been devoted to analysing thermodynamic models for solid
dispersions with a view to identifying regions in the phase diagram where
amorphous phase separation or drug recrystallization can occur. However,
detailed partial differential equation non-equilibrium models that track the
evolution of solid dispersions in time and space are lacking. Hence theoretical
predictions for the timescale over which phase separation occurs in a solid
dispersion are not available. In this paper, we address some of these
deficiencies by (i) constructing a general multicomponent diffusion model for a
dissolving solid dispersion; (ii) specializing the model to a binary
drug/polymer system in storage; (iii) deriving an effective concentration
dependent drug diffusion coefficient for the binary system, thereby obtaining a
theoretical prediction for the timescale over which phase separation occurs;
and (iv) presenting a detailed numerical investigation of the HPMCAS/Felodipine
system assuming a Flory-Huggins activity coefficient. The numerical simulations
exhibit numerous interesting phenomena, such as the formation of polymer
droplets and strings, Ostwald ripening/coarsening, phase inversion, and
droplet-to-string transitions.
