Dual-Nanochannel MZP@HKUST-1 Composite Membranes for Organic Solvent Nanofiltration in Pharmaceutical Separations

Organic solvent nanofiltration (OSN) membranes are critically important for the efficient and sustainable separation of active pharmaceutical ingredients (APIs) from low-molecular-weight genotoxic impurities (GTIs). However, conventional polymer OSN membranes face significant technical challenges in improving APIs separation accuracy due to their inherent chain flexibility and undefined pore structure. Herein, we report an imidazole-based nanoparticle (MZP)-mediated confined crystallization strategy to fabricate MZP@HKUST-1 nanocomposite membranes with rigid and well-defined pore structures. The MZP nanoparticles serve as a porous coordination template that guides the controlled growth of HKUST-1 within a polymeric network, yielding a rigid selective layer with dual-micropores structure (0.44 and 0.68 nm) and high surface area (717.6 m 2 g -1 ). The resulting membrane exhibits exceptional methanol permeance (24.3 L·m -2 ·h -1 ·bar -1 ) and precise molecular sieving, achieving >98% rejection for solutes larger than 0.8 nm while allowing smaller molecules to pass quickly. In a representative pharmaceutical separation, the membrane demonstrates a high separation factor of 49.0 for vitamin B1/naringin, an 8.4-fold improvement over the pristine MZP membrane. Moreover, the membrane shows outstanding long-term stability (>200 h) and anti-fouling properties, and a scaled-up membrane (460 cm 2 ) successfully purifies naringin to 99.5% purity in a multistage process, outperforming commercial OSN benchmarks. This work provides a versatile and scalable platform to precisely engineer MOF-based membranes for high-precision molecular separations in the pharmaceutical and chemical industries.