Biomimetic molecularly imprinted hollow fiber membranes for continuous Enantioseparation of amlodipine

Abstract

Critical chiral separation is critically important in pharmaceutical development since enantiomers often exhibit markedly different pharmacological profiles, as exemplified by amlodipine where the (S)-enantiomer exhibits potent antihypertensive activity while the (R)-counterpart shows negligible therapeutic effect. Such dramatic differences in bioactivity necessitate the development of efficient enantioseparation technologies to ensure drug safety and efficacy. We have developed a novel biomimetic separation system employing molecularly imprinted hollow fiber membranes (MIMs) for the efficient resolution of racemic amlodipine. The molecular imprinting process involves polymerization in the presence of the target (S)-amlodipine template, creating cavities with tailored shape and functional groups that exhibit selective rebinding affinity. These membranes synergistically combine the high surface area and excellent mass transfer properties of hollow fiber substrates with the precise molecular recognition capabilities of molecularly imprinted polymers (MIPs). The MIP layer, functioning as artificial antibody mimics, was specifically designed to recognize and capture the target (S)-amlodipine enantiomer with high fidelity. The covalent/non-covalent interactions between the template and functional monomers during imprinting ensure optimal stereochemical complementarity for chiral discrimination. Remarkably, this system achieves exceptional chiral separation performance without requiring any external chiral selectors. The optimized MIMs demonstrate an outstanding separation factor (α) of 3.79 within a remarkably short processing time of just 5 min. This exceptional performance stems from the unique combination of the hollow fiber's convective flow characteristics and the MIP's selective binding sites, which together enable both high throughput and precise enantiomeric discrimination. The practical advantages of this technology extend beyond its separation performance. The membrane fabrication process is straightforward and reproducible, while the modular nature of hollow fiber systems allows for seamless scale-up to industrial production levels. These attributes position our MI-HFM technology as a transformative platform for the commercial-scale production of enantiopure pharmaceuticals, offering significant advantages over conventional separation methods in terms of both efficiency and cost-effectiveness. The successful implementation of this approach could substantially improve the economic viability of single-enantiomer drug manufacturing while ensuring higher product purity. Looking forward, this technology platform shows considerable potential for adaptation to other chiral separation challenges in the pharmaceutical industry.