Green strategy to produce large core–shell affinity beads for gravity-driven API purification processes

In this work, Molecular Imprinted Polymers (MIPs)-layered silica beads which have affinity for a model pharmaceutical impurity, acetamide (ACET) were developed using supercritical carbon dioxide (scCO₂) technology. Silica beads were first functionalized using two different green strategies, grafting to (MPS/EtOH in scCO₂) and grafting from (plasma technology). These core beads were then used as seed particles in the synthesis, in scCO₂ of a MIP layer. Dynamic binding tests were performed in order to evaluate the affinity of the resulting silica core – MIP shell beads to ACET and the efficiency of its removal from an active pharmaceutical ingredient – Beclomomethasone dipropionate (API) crude mixture. ACET was preferentially retained over analogue molecules, benzamide (BENZ) and pivalamide (PIV). The core–shell MIP beads were packed in a SPE column (396.5 mg in a 3 mL SPE tube) and evaluated as a potential gravity-driven purification device, enabling the removal of 100% of ACET whilst losing only 0.37% of API from a model mixture solution—10 mL of ACET and API (0.25 mg mL⁻¹ + 3.5 mg mL⁻¹).