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Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling

2002; Wiley; Volume: 19; Issue: 5 Linguagem: Inglês

10.1002/1521-4117(200211)19

1521-4117

Michael Türk, B. Helfgen, P. Hils, R. Lietzow, Karlheinz Schaber,

Subcritical and Supercritical Water Processes

Particle & Particle Systems CharacterizationVolume 19, Issue 5 p. 327-335 Review Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling Michael Türk, Michael Türk [email protected] Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorBritta Helfgen, Britta Helfgen Degussa AG, VT-P, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany.Search for more papers by this authorPeter Hils, Peter Hils Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorRalph Lietzow, Ralph Lietzow Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorKarlheinz Schaber, Karlheinz Schaber Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this author Michael Türk, Michael Türk [email protected] Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorBritta Helfgen, Britta Helfgen Degussa AG, VT-P, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany.Search for more papers by this authorPeter Hils, Peter Hils Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorRalph Lietzow, Ralph Lietzow Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this authorKarlheinz Schaber, Karlheinz Schaber Universität Karlsruhe (TH), Institut für Technische Thermodynamik und Kältetechnik, Engler-Bunte-Ring 21, 76131 Karlsruhe, Germany.Search for more papers by this author First published: 04 November 2002 https://doi.org/10.1002/1521-4117(200211)19:5 3.0.CO;2-VCitations: 55AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract An increasing number of newly developed pharmaceutical substances are poorly soluble in both aqueous and organic media. Thus, the application of oral or injectable drugs is often limited by its low bioavailability. An alternative and promising method to improve the bioavailability of pharmaceutical agents is the production of nanoscale particles by the rapid expansion of supercritical solutions (RESS). Our research is aimed towards an improved understanding of the underlying physical phenomena of the relationship between the process conditions and the particle characteristics. Therefore, experimental investigations and numerical simulations were performed. RESS experiments with the pharmaceutical substances β-sitosterol, griseofulvin, and ibuprofen led to particle sizes in the range of 240±80 nm. In addition, as one step towards intravenous application of poorly soluble drugs, β-sitosterol was used to produce aqueous suspensions of a water-insoluble drug with a particle size smaller than or equal to those produced by RESS into air. RESS modeling is focused on the flow through the nozzle, the supersonic free jet, the mach shock, and particle growth in the expansion unit. The comparison with experimental results shows a good agreement in the general trends but does not match exactly the measured mean particle sizes. References 1 R. H. Müller, B. H. L. Böhm, M. J. Grau, Nanosuspensionen – Formulierungen für schwerlösliche Arzneistoffe mit geringer Bioverfügbarkeit, 1. Mitteilung: Herstellung und Eigenschaften, 2. Mitteilung: Stabilität, biopharmazeutische Aspekte, mögliche Arzneiformen und Zulassungsfragen. Pharm. Ind. 1999, 61, 74–78, 175-178. 2 B. Subramaniam, R. A. Rajewski, K. Snavely, Pharmaceutical Processing with Supercritical Carbon Dioxide. J. Pharm. 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