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Active Pharmaceutical Ingredients (APIs) manufacturing requires a three-step batch process, including crystallization, followed by filtration and drying, which is energy-intensive and requires the use of significant amounts of solvents per mass of API produced. These methods are often inefficient and lead to product loss, contamination risks, and variable particle properties. Percrystallization (PerX) is an emerging membrane crystallization technology that enables the continuous production of dry crystals in a single step. While prior PerX studies have primarily focused on aqueous systems, this work investigates PerX using solvents relevant to pharmaceutical manufacturing. Using α-alumina and modified carbon coated membranes, the effect of solvent properties on membrane wettability and solvent flux was analyzed. Results show that the PerX process involves a first step of membrane wetting and solvent penetration, followed by its evaporation near/at the pores mouth on the downstream side of the membrane. The α-alumina membrane consistently outperformed the modified membrane when processing solvents, which is attributed to its higher wettability. Ibuprofen crystallization was successfully demonstrated in ethanol, methanol, acetone, and acetonitrile. PerX achieved high crystallization yields (>95%) under mild temperatures, consistently producing the stable polymorphic Form I with 99.9% purity and residual solvents below ICH Q3C limits. Compared with commercial ibuprofen, PerX-derived crystals exhibited plate-like morphology, which confers superior mechanical properties than the needle-like particles typically observed. This study confirms the feasibility of PerX for solvent-based crystallization of APIs with complete solvent recovery and integrated crystal isolation and drying, highlighting its potential for continuous pharmaceutical manufacturing with reduced process complexity and downstream processing demand.
Sequeira et al. (Tue,) studied this question.