Dokument: Solid form analysis with special consideration of perfusion calorimetry
| Titel: | Solid form analysis with special consideration of perfusion calorimetry | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=12172 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20090721-100522-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Baronsky, Julia [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Urbanetz, Nora Anne [Gutachter] Prof. Dr. Kleinebudde, Peter [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | A substance may exist in several solid forms that differ with regard to the three dimensional structure and / or the number and type of components present. Solid forms may have different physical and chemical properties. Examples of crystalline solid forms are modifications and solvates. In case of modifications (mod.), the crystal lattices are built by molecules of the substance only while in case of solvates, the lattices additionally contain solvent molecules. If the solvent is water, the solvates will be named hydrates. As active pharmaceutical ingredients (APIs) and excipients present in a drug product may also exist in different solid forms which may have a considerable impact on efficacy, performance and safety of the drug product, it is necessary to control the solid forms of APIs and excipients. For this, the forms have to be known and characterised. One method to characterise solid forms is perfusion calorimetry in which the sample is subjected to a certain relative vapour pressure of solvent while measuring thermal activity. It allows the study of the interaction between solid forms and solvent vapours. Up to now, the potential of perfusion calorimetry in solid form analysis has barely been used.
In this study, the solid forms of APIs were studied and the potential of perfusion calorimetry in solid form analysis was explored with the aim to contribute to the understanding of solid forms. The APIs investigated were toltrazuril for which a solid form screening was performed and emodepside whose solid forms I IV were characterised in order to analyse the state of water in the forms. The potential of perfusion calorimetry in the characterisation of both substances was examined. In order to be able to reliably perform perfusion calorimetry, a general method to test the perfusion systems used to control the relative vapour pressure of solvent during measurement was developed. In addition, the use of perfusion calorimetry in a new application field, the characterisation of solvates that retain their crystal structures upon desolvation (formation of isomorphic desolvates), was investigated. The solid form screening performed for toltrazuril resulted in the mod. B, C and D. Mod. D and C are both monotropically related to mod. B, while mod. D and C are enantiotropically related. Regarding emodepside, the characterisation of the solid forms I IV revealed that form I represents a modification while the forms II IV are hydrates forming isomorphic desolvates. A general method to test perfusion systems was successfully developed so that perfusion calorimetry could be reliably performed. In case of toltrazuril, perfusion calorimetry was helpful to determine the relative stabilities of the modifications. Regarding emodepside, perfusion calorimetry indicated the transition of the desolvates II IV into the isomorphic hydrates II IV. The investigation of further solvates forming isomorphic desolvates confirmed the general suitability of the method to indicate the presence of this type of solvate. The analysis of the solid forms of the APIs and the study of the potential of perfusion calorimetry successfully contributed to the understanding of solid forms, especially of solvates forming isomorphic desolvates. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 20.07.2009 | |||||||
| Dateien geändert am: | 20.07.2009 | |||||||
| Promotionsantrag am: | 20.05.2009 | |||||||
| Datum der Promotion: | 02.07.2009 |
