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Can Organic Solvent Nanofiltration (OSN) be considered green? Is OSN greener than other downstream processing technologies? These are the two main questions addressed critically in the present review. Further questions dealt with in the review are as follows: What is the carbon footprint associated with the fabrication and disposal of membrane modules? How much solvent has to be processed by OSN before the environmental burden of OSN is less than the environmental burden of alternative technologies? What are the main challenges for improving the sustainability of OSN? How can the concept of Quality by Design (QbD) improve and assist the progress of the OSN field? Does the scale have an effect on the sustainability of membrane processes? The green aspects of OSN membrane fabrication, processes development and scale-up as well as the supporting concept of QbD, and solvent recovery technologies are critically assessed and future research directions are given, in this review. Gyorgy Szekely Gyorgy received his MSc degree in Chemical Engineering from the Technical University of Budapest, and he earned his PhD degree in Chemistry under Marie Curie Actions from the Technical University of Dortmund. He worked as an Early Stage Researcher in Hovione PharmaScience and an IAESTE Fellow at the University of Tokyo. He is currently a Research Associate in Imperial College London. His multidisciplinary professional background covers supramolecular chemistry, organic and analytical chemistry, molecular recognition, molecular imprinting, process development, nanofiltration and pharmaceutical impurity scavenging. He is the Secretary General of the Marie Curie Fellows Association and a Member of the Royal Society of Chemistry.

Tackling the wastewater challenge in polymer membrane manufacturing with a continuous adsorption process.

alkylation of the second nitrogen of the piperazine ring with the genotoxic reagent 4-chloro-1-bromobutane (Scheme 10). 64 APIs streams may contain genotoxic alkyl halides impurities when a reaction takes place in alcoholic solvent at reflux temperature in the presence of hydrogen halides or alkali halides and strong acids. These reaction conditions may be applied in cyclization, decarboxylation, sulfonyl cleavage, Narylation and API salt formation. Note that this list is not exhaustive. For instance, capecitabine is a chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. 65 During its synthesis, D-ribose is heated under reflux in methanol in the presence of concentrated HCI and acetone Scheme 2. O-Alkylation of Isovanillin during the Synthesis of Aliskiren Using Genotoxic 1,3-Dibromopropane Scheme 3. Use of Methyl Iodide in the Preparation of Cerivastatin Scheme 4. S-Alkylation with Methyl Iodide during the Last Synthetic Step of Lamifiban Scheme 5. S-Alkylation with Methyl Iodide during the Synthesis of Eldacimibe Scheme 6. N-Methylation with Genotoxic Methyl Iodide during the Preparation of Efegatran Scheme 7. Quaternization by Means of Methyl Iodide during Milameline Synthesis Scheme 8. Direct Use of Genotoxic 2-Iodopropane in the Synthesis of Latanoprost Scheme 9. Use of Genotoxic 2-Bromopropane and Nitrogen Mustard during the Synthesis of Mazapertine

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The effect of crosslinker, functional monomer and extraction on the long-term performance and degradation of molecularly imprinted polymers was investigated through adsorption studies, NMR, SEM, TGA and BET.

Membrane processes suffer limitations such as low product yield and high solvent consumption, hindering their widespread application in the pharmaceutical and fine chemicals industries. In the present work, the authors propose an efficient purification methodology employing a two-stage cascade configuration coupled to an adsorptive solvent recovery unit, which addresses the two limitations. The process has been validated on purification of active pharmaceutical ingredient (API) from genotoxic impurity (GTI) using organic solvent nanofiltration (OSN). The model system selected for study comprises roxithromycin macrolide antibiotic (Roxi) with 4-dimethylaminopyridine (DMAP) and ethyl tosylate (EtTS) as API and GTIs, respectively. By implementing a two-stage cascade configuration for membrane diafiltration, the process yield was increased from 58% to 95% while maintaining less than 5 ppm GTI in the final solution. Through this yield enhancement, the membrane process has been "revamped" from an unfeasible process to a highly competitive unit operation when compared to other traditional processes. The advantage of size exclusion membranes over other separation techniques has been illustrated by the simultaneous removal of two GTIs from different chemical classes. In addition, a solvent recovery step has been assessed using charcoal as a non-selective adsorbent, and it has been shown that pure solvent can be recovered from the permeate. Considering the costs of solvent, charcoal, and waste disposal, it was concluded that 70% solvent recovery is the cost-optimum point. Conventional single-stage diafiltration (SSD) and two-stage diafiltration (TSD) configurations were compared in terms of green metrics such as cost, mass and solvent intensity, and energy consumption. It was calculated that implementation of TSD, depending on the batch scale, can achieve up to 92% cost saving while reducing the mass and solvent intensity up to 73%. In addition, the advantage of adsorptive solvent recovery has been assessed revealing up to 96% energy reduction compared to distillation and a 70% reduction of CO 2 footprint.

A continuous oleuropein isolation process using imprinted materials coupled with nanofiltration-based solvent recovery utilising olive leaf waste.