Design, preparation and characterization of novel molecularly imprinted polymers for removal of potentially genotoxic 1,3-diisopropylurea from API solutions
This paper describes the design and synthesis of novel molecularly imprinted polymers (MIPs) for the selective removal of a potentially genotoxic impurity (GTI) from active pharmaceutical ingredient (API) post reaction streams. Due to safety concerns, concn. levels of GTIs allowed in pharmaceutical products have been driven down to stringent low values. Therefore, novel MIPs have been prepd. with the aim to address this challenge. The model mols. selected for this study were 1,3-diisopropylurea (IPU), as a potential GTI and keppra (KP), mometasone furoate (Meta) and roxithromycin (Roxi), as APIs. The MIPs were prepd. using IPU as template and methacrylic acid (MAA), in the free acid or anionic form, as functional monomer. Typically, in industrial post reaction streams, API concns. are significantly higher than those of IPU. Therefore, the novel MIPs were tested under such a scenario. To test the effect of different host-guest interactions, MIP1 and MIP2 were prepd. in the absence and presence of a base, resp. A highest degree of IPU binding, at a value of 80%, was obtained for MIP2, with only 15% non-specific binding of APIs, regardless of API size and chem. structure. The enhanced performance of MIP2 is in agreement with the incorporation of a carboxylate anion in the MIP, which interacts more strongly with IPU than the neutral free acid.