Continuous flow synthesis concatenated with continuous flow liquid–liquid extraction for work-up and purification: selective mono- and di-iodination of the imidazole backbone

Abstract

Flow processes for mono- and di-iodination of the imidazole backbone were devised, developed, and implemented on the multi-jet oscillating disk (MJOD) flow reactor platform.

Process modelling, design and technoeconomic Liquid–Liquid Extraction (LLE) optimisation for comparative evaluation of batch vs. continuous pharmaceutical manufacturing of atropine

“…Significant efforts in modelling and simulation in pursuit of continuous pharmaceutical separation process development have been demonstrated in recent years. Implementation of combined experimental and modelling approaches towards integrated LLE design in the literature for pharmaceutical purifications and separations demonstrate the utility of theoretical methods in establishing optimal design and operating parameters (Drageset and Bjørsvik, 2016;Monbaliu et al, 2016;Weeranoppanant et al, 2017). Mathematical optimisation can be used to identify cost optimal process designs for pharmaceutical manufacturing campaigns (Gross and Roosen, 1998;Patrascu and Barton, 2018); plantwide modelling and optimisation with a focus on optimal continuous separation process design towards total cost minimisation have been implemented by our group for numerous APIs (Jolliffe and Gerogiorgis, 2017a,b;Diab and Gerogiorgis, 2018b).…”

Design Space Identification and Visualization for Continuous Pharmaceutical Manufacturing

“…That said, there have been a few experimental as well as theoretical studies on the design of continuous LLE processes. Drageset and Bjørsvik (2016) performed an in-line continuous LLE for purification of a reactor product mixture prior to further downstream processing, allowing for significant material reduction compared to the batch purification process [19]. Monbaliu et al (2016) also implemented a continuous LLE process as part of an end-to-end CPM process for lidocaine hydrochloride (a local anesthetic) from synthesis to aqueous formulation [20].…”

“…Monbaliu et al (2016) also implemented a continuous LLE process as part of an end-to-end CPM process for lidocaine hydrochloride (a local anesthetic) from synthesis to aqueous formulation [20]. Implementation of combined experimental and modeling approaches towards integrated LLE design described in the literature for pharmaceutical purifications and separations demonstrate the utility of theoretical methods in establishing optimal design and operating parameters [19][20][21].…”

Process Design and Optimization for the Continuous Manufacturing of Nevirapine, an Active Pharmaceutical Ingredient for HIV Treatment

“…Modeling and optimization methodologies can be used to establish optimal process design configurations. , Advanced theoretical methods have been previously implemented toward optimal pharmaceutical unit design and optimization of pharmaceutical manufacturing processes to elucidate optimal operation, analysis of synthetic pathways, − and life cycle assessments. , Modeling and optimization have also been implemented in the design of separation processes in pharmaceutical manufacturing, such as liquid–liquid extraction (LLE), − crystallization, − and chromatographic methods . Identification of cost-optimal plantwide designs is essential, particularly end-to-end designs encompassing synthesis and purification/separation.…”