Green approach on the development of lock-and-key polymers for API purification

Purification is a crucial stage of API (Active Pharmaceutical Ingredients) manufacturing processes. While it ensures final quality specifications it also represents a significant part of manufacturing costs. In this work we have developed cheap acrylate and acrylamide-based affinity polymers by molecular imprinting in supercritical carbon dioxide (scCO(2)). This green strategy yielded ready-to-use Molecularly Imprinted Polymers (MIPs) with lock-and-key affinity for a model pharmaceutical impurity, acetamide, which has potential application in API manufacturing processes. MIPs generated, along with their corresponding non-imprinted controls, were characterized by SEM (Scanning electron microscopy), ASAP (nitrogen adsorption porosimetry), FTIR (Fourier Transform Infra-red spectroscopy) and particle size distribution. Static and dynamic binding and selectivity experiments were performed in order to evaluate affinity and selectivity of the polymeric matrices for the template and molecules from the same family, benzamide and pivalamide. Better adsorption affinity results were obtained for MIPs in comparison with NIPs. Methacrylamide (MAM) based MIP showed the best performance, adsorbing 2.21 mmol.g pol(-1) of acetamide, when acetonitrile was used as co-solvent in the polymerization. MIPs also showed a higher selectivity for acetamide than for benzamide and pivalamide. Additionally, adsorption data were further correlated with Langmuir, Scatchard (as a second linearization form of the Langmuir model), Freundlich and Temkin equations. The promising results obtained in this work support the potential application of these affinity devices in API purification. (C) 2016 Elsevier B.V. All rights reserved.