Integrated crystallization, drying, and particle engineering of ibuprofen microcrystals with enhanced flowability using percrystallization.

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⁻2memb 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.