Self-limiting interfacial synthesis of inorganic thin films for high-performance organic solvent nanofiltration in pharmaceutical applications

Inorganic membranes are prime candidates for organic solvent recovery in the pharmaceutical industry due to their excellent solvent resistance, mechanical strength and durability. However, constructing high-performance inorganic separation layers is still the most challenging aspect in the fabrication of inorganic membranes for organic solvent nanofiltration (OSN). Prussian blue analogues (PBAs) exhibit high chemical stability for their rigid cubic framework with strong covalent metal-cyanide coordination bonds. Inspired by the interfacial polymerization (IP) strategy, this study proposes a simple synthesis method for prussian blue analog thin films (PBA TFs) on porous ceramic substrates, using coordination reactions between K₃[Fe(CN)₆] and acetylacetonate (e.g. Cu(acac)₂, Mn(acac)₃ or Co(acac)₂). The Mn-Fe PBA membrane exhibits high solvent permeance (e.g., 176.4 L·m⁻²·h⁻¹·bar⁻¹ for ethyl acetate) and demonstrates a molecular weight cut-off ranging from 665 to 760 Da across six tested solvents. To evaluate the industrial potential of Mn-Fe PBA membranes, solvent recovery experiments were conducted in a twin-stage OSN system using seven active pharmaceutical ingredient (API)/solvent systems. In the tylosin/dimethyl sulfoxide system, the Mn-Fe PBA membrane achieved over 80 % total API retention, maintaining stable performance across multiple cycles. The formation process of PBA TFs was analyzed by adjusting monomer diffusion conditions. Furthermore, molecular dynamics simulations elucidated the film formation mechanism. The self-limiting nature of the IP strategy not only inhibits the formation of PBA large crystals, but also induces the self-assembly of PBA nanocrystals along the n-hexane/water interface, resulting in a complete PBA TF. This IP strategy blazes a new trail for fabrication of high-performance inorganic OSN membranes.