Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review
An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). I...
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| Format: | Article |
| Language: | English |
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Multidisciplinary Digital Publishing Institute
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/118430/ http://psasir.upm.edu.my/id/eprint/118430/1/118430.pdf |
| _version_ | 1848867514996490240 |
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| author | Lee, Jia Lin Chong, Gun Hean Ota, Masaki Guo, Haixin |
| author_facet | Lee, Jia Lin Chong, Gun Hean Ota, Masaki Guo, Haixin |
| author_sort | Lee, Jia Lin |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or solvent mixtures, 2-methyl tetrahydrofuran in methanol, HCl in cyclopentyl methyl ether, or trifluoroacetic acid in propylene carbonate or surfactant water (no organic solvents) are suggested replacement solvents. For the replacement of dichloromethane (DCM) used in chromatography, ethyl acetate ethanol or 2-propanol in heptanes, with or without acetic acid or ammonium hydroxide additives, are suggested, along with methanol acetic acid in ethyl acetate or methyl tert-butyl ether, ethyl acetate in ethanol in cyclohexane, CO2 -ethyl acetate, CO2 -methanol, CO2 -acetone, and CO2 -isopropanol. Supercritical CO2 (scCO2 ) can be used to replace many organic solvents used in processing materials from natural sources. Vegetable, drupe, legume, and seed oils used as co-extractants (mixed with substrate before extraction) can be used to replace the typical organic co-solvents (ethanol, acetone) used in scCO2 extraction. Mixed solvents consisting of a hydrogen bond donor (HBD) solvent and a hydrogen bond acceptor (HBA) are not addressed in GSK or CHEM21 solvent replacement guides. Published data for 100 water-soluble and water-insoluble APIs in mono-solvents show polarity ranges appropriate for the processing of APIs with mixed solvents. When water is used, possible HBA candidate solvents are acetone, acetic acid, acetonitrile, ethanol, methanol, 2-methyl tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, or diformylxylose. When alcohol is used, possible HBA candidates are cyclopentanone, esters, lactone, eucalytol, MeSesamol, or diformylxylose. HBA—HBA mixed solvents, such as Cyrene—Cygnet 0.0, could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft parameters, and linear solvation energy relationships provide practical ways for identifying mixed solvents applicable to API systems. |
| first_indexed | 2025-11-15T14:37:43Z |
| format | Article |
| id | upm-118430 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:37:43Z |
| publishDate | 2024 |
| publisher | Multidisciplinary Digital Publishing Institute |
| recordtype | eprints |
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| spelling | upm-1184302025-07-10T04:05:09Z http://psasir.upm.edu.my/id/eprint/118430/ Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review Lee, Jia Lin Chong, Gun Hean Ota, Masaki Guo, Haixin An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or solvent mixtures, 2-methyl tetrahydrofuran in methanol, HCl in cyclopentyl methyl ether, or trifluoroacetic acid in propylene carbonate or surfactant water (no organic solvents) are suggested replacement solvents. For the replacement of dichloromethane (DCM) used in chromatography, ethyl acetate ethanol or 2-propanol in heptanes, with or without acetic acid or ammonium hydroxide additives, are suggested, along with methanol acetic acid in ethyl acetate or methyl tert-butyl ether, ethyl acetate in ethanol in cyclohexane, CO2 -ethyl acetate, CO2 -methanol, CO2 -acetone, and CO2 -isopropanol. Supercritical CO2 (scCO2 ) can be used to replace many organic solvents used in processing materials from natural sources. Vegetable, drupe, legume, and seed oils used as co-extractants (mixed with substrate before extraction) can be used to replace the typical organic co-solvents (ethanol, acetone) used in scCO2 extraction. Mixed solvents consisting of a hydrogen bond donor (HBD) solvent and a hydrogen bond acceptor (HBA) are not addressed in GSK or CHEM21 solvent replacement guides. Published data for 100 water-soluble and water-insoluble APIs in mono-solvents show polarity ranges appropriate for the processing of APIs with mixed solvents. When water is used, possible HBA candidate solvents are acetone, acetic acid, acetonitrile, ethanol, methanol, 2-methyl tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, or diformylxylose. When alcohol is used, possible HBA candidates are cyclopentanone, esters, lactone, eucalytol, MeSesamol, or diformylxylose. HBA—HBA mixed solvents, such as Cyrene—Cygnet 0.0, could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft parameters, and linear solvation energy relationships provide practical ways for identifying mixed solvents applicable to API systems. Multidisciplinary Digital Publishing Institute 2024-04-09 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/118430/1/118430.pdf Lee, Jia Lin and Chong, Gun Hean and Ota, Masaki and Guo, Haixin (2024) Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review. Liquids, 4 (2). pp. 352-381. ISSN 2673-8015 https://www.mdpi.com/2673-8015/4/2/18 10.3390/liquids4020018 |
| spellingShingle | Lee, Jia Lin Chong, Gun Hean Ota, Masaki Guo, Haixin Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title | Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title_full | Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title_fullStr | Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title_full_unstemmed | Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title_short | Solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| title_sort | solvent replacement strategies for processing pharmaceuticals and bio-related compounds: a review |
| url | http://psasir.upm.edu.my/id/eprint/118430/ http://psasir.upm.edu.my/id/eprint/118430/ http://psasir.upm.edu.my/id/eprint/118430/ http://psasir.upm.edu.my/id/eprint/118430/1/118430.pdf |