Impact of solvents during wet stirred media milling of cross-linked biopolymer suspensions

The aim of this study was to examine the impact of solvents during the wet stirred media milling of cross-linked biopolymers considering breakage kinetics, physical stability of the suspensions, and microhydrodynamics. To this end, a model cross-linked biopolymer, sodium starch glycolate (SSG), was milled in acetone and water wherein SSG was non-swellable and swellable, respectively. Suspensions containing SSG particles with and without two stabilizers, i.e., hydroxypropyl cellulose and sodium dodecyl sulfate, were prepared. The temporal evolution of the SSG particle size during the milling was tracked by laser diffraction. Swelling of the SSG particles in water was independently characterized using microscopy and laser diffraction, which revealed fast swelling within a few minutes. Results also suggest that SSG particles were broken faster in water than in acetone, and stabilizers could not prevent severe aggregation in acetone. Despite the greater viscous dampening in water, water was more favorable for faster production of stable suspensions than acetone. The superior performance of aqueous milling was primarily attributed to favorable nanoparticle stabilization in water and secondarily to swelling-induced softening and coarsening of SSG particles. Hence, also being environmentally benign and safe, it is preferred over organic solvent-based milling for the preparation of cross-linked biopolymer nanosuspensions.