Dokument: Hot-melt extrusion with poorly soluble drugs
| Titel: | Hot-melt extrusion with poorly soluble drugs | |||||||
| Weiterer Titel: | Schmelzextrusion mit schwer löslichen Arzneistoffen | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=8384 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20080910-120540-2 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Albers, Jessica [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Kleinebudde, Peter [Gutachter] Prof. Dr. Breitkreutz, Jörg [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Hot-melt extrusion with poorly soluble drugs is a challenging method to enhance solubility. The formation of solid dispersions leads to metastable systems that have advantageous dissolution behaviour.
The hot-melt extrusion process is influenced by several parameters. The right coordination of the parameters is decisive for the production of solid dispersions and thus, the success in solubility enhancement. Besides the configuration of the screw and the temperature profile of the barrel, the design of the die plate represents the third important extrusion parameter. Basic butylated methacrylate copolymer is a suitable carrier to enhance the solubility of the poorly water-soluble drug celecoxib in a hot-melt extrusion process. The best solubility enhancement can be obtained by dispersing the drug in the molten carrier on a molecular basis and thus, to form glassy solid solutions. Glassy solid solutions of celecoxib and basic butylated methacrylate copolymer have a fast dissolution rate and result in a 58 fold supersaturated solution. The mechanism of drug release from these glassy solid solutions is carrier-controlled and governed by dissolution. The enhancement of the dissolution rate is based on improved solubility and wettability. The hot-melt extrusion process is highly dependent on the physicochemical properties of the compounds and their miscibility in the molten state. The use of basic butylated methacrylate copolymer as solubility enhancing carrier in hot-melt extrusion cannot be transferred to all drugs. Thus, each formulation has to be analyzed separately. A combined approach of tools predicting miscibility is highly appropriate, as no single technique may yield all the required information. Nevertheless, the evaluation of the melting behaviour via DSC has the highest impact. Hot-melt extruded glassy solid solutions can be processed into solid dosage forms. The mechanical energy input through milling and tabletting has no influence on the solid-state stability. The solution-state stability can be achieved by adding HPMC to the external phase. The filling of capsules with milled hot-melt extrudates is a promising technique to obtain solid dosage forms from glassy solid solutions. By the extensive analysis of the hot-melt extrusion process, the interactions of the compounds, the thermal characteristics, and the dissolution mechanism of the resulting systems, it is possible to predict the extrusion process in an early stage of development and to improve the dissolution of poorly soluble drugs. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 10.09.2008 | |||||||
| Dateien geändert am: | 07.07.2008 | |||||||
| Promotionsantrag am: | 19.05.2008 | |||||||
| Datum der Promotion: | 27.06.2008 |
