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Insight into the Me...
Insight into the Mechanisms of Cocrystallization of Pharmaceuticals in Supercritical Solvents
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- Padrela, Luis (author)
- Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa
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- Rodrigues, Miguel A. (author)
- Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa, Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa
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- Tiago, João (author)
- Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa
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- Velaga, Sitaram (author)
- Luleå tekniska universitet,Medicinsk vetenskap
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- Matos, Henrique A. (author)
- Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa, Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa
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- de Azevedo, Edmundo Gomes (author)
- Department of Chemical Engineering and Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Department of Chemical and Biological Engineering, Instituto Superior Técnico, Lisboa
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(creator_code:org_t)
- 2015-05-29
- 2015
- English.
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In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 15:7, s. 3175-3181
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Carbon dioxide has been extensively used as a green solvent medium for the crystallization of active pharmaceutical ingredients (APIs) by replacing harmful organic solvents. This work explores the mechanisms underlying a novel recrystallization method-cocrystallization with supercritical solvent (CSS)-which enables APIs cocrystallization by suspending powders in pure CO2. Six well-known APIs that form cocrystals with saccharin (SAC) were processed by CSS, namely, theophylline (TPL), indomethacin (IND), carbamazepine (CBZ), caffeine (CAF), sulfamethazine (SFZ), and acetylsalicylic acid (ASA). Pure cocrystals were obtained for TPL, IND, and CBZ (with SAC) after 2 h of CSS processing. Convection was revealed to be a determining parameter for successful cocrystallization with high-yield levels. TPL-SAC was selected as a model system to study the cocrystallization kinetics in the gas, supercritical, and liquid phases under different conditions of pressure (8-20 MPa), temperature (30 to 70 degrees C), and convection regimes. The solubility of each substance in CO2 was measured at the selected working conditions. TPL-SAC showed a cocrystallization rate of 2.9% min(-1), two times higher than that of IND-SAC, due to the higher solubility of TPL in CO2. The cocrystallization kinetics was also improved by increasing the CO2 density, showing that cocrystallization was limited by the dissolution of cocrystal formers. Overall, the CSS process has a potential for scale-up as a novel, simple, solvent-free batch process whenever the cocrystal phase is formed in the CO2 media.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Annan hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Other Health Sciences (hsv//eng)
Keyword
- Health Science
- Hälsovetenskap
Publication and Content Type
- ref (subject category)
- art (subject category)
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