• A single unit operation integrates crystallization, drying, and particle engineering. • High-throughput ibuprofen processing was achieved with controlled crystal attributes. • Dry ibuprofen crystals were produced directly in one processing step. • Percrystallization yielded ibuprofen powders with markedly improved flowability. • Crystal size was engineered via solvent evaporation rate control. Crystallization, filtration, and drying remain key but limiting operations in Active Pharmaceutical Ingredient (API) manufacturing. Membrane percrystallization (PerX) is a new approach that couples solvent removal and crystallization within a single unit operation. In this study, PerX was evaluated for ibuprofen crystallization under different feed concentrations and temperatures. The resulting solids were assessed in terms of throughput, solid-state quality, and particle attributes relevant to downstream handling. PerX achieved high crystallization yields (>95%) and fluxes up to 5.13 kg API m⁻ 2 memb h⁻ 1 . Across all operating conditions, ibuprofen was consistently obtained as the stable Form I, with purity above 99.9%, residual solvent contents within the applicable ICH Q3C limits, and low moisture levels without a separate drying step. Compared with commercial ibuprofen, PerX-derived crystals showed plate-like morphology, smaller particle sizes ( dv50 between 3.9 and 10.2 µm), and improved powder flowability. These results demonstrate that PerX can integrate crystallization and drying while enabling control over crystal attributes in a single intensified step.
Sequeira et al. (Wed,) studied this question.