Networked Porous Organic Cage Membranes for Precision Separation of Pharmaceutical Ingredients

Organic solvent nanofiltration (OSN) membranes play a crucial role in the manufacturing of active pharmaceutical ingredients (APIs). The synthesis process of APIs typically contains low molecular weight genotoxic impurities (GTIs) that compromise product quality. However, current OSN membranes face significant technical challenges in separating high-value APIs with molecular weights (MW) below 350 g mol^-1 due to their lack of precisely controlled pore structures. Porous organic cages (POCs), a class of discrete organic molecules with permanent three-dimensional cavities, feature ordered pore structures, good processability and modularity, making them ideal candidates for fabricating membranes with highly tunable pore structures for precise separations. Here, we report the fabrication of porous network membranes via nucleophilic substitution reactions of POCs. These membranes, with retaining incorporated cavities, exhibit high methanol permeance and excellent dye rejection (>94% for APIs with MW above 368 g mol^-1), outperforming commercial OSN membranes. Importantly, they achieve a selectivity of 13 in removing GTIs from APIs, thereby producing high-purity APIs. This work highlights the great potential of the POCs-based membranes for precision pharmaceutical separations.