Top-Down Analyse des Zustandes und des Herstellungsprozesses einer multiplen Emulsion

Im Rahmen dieser Arbeit werden multiple Wasser-in-Öl-in-Wasser Emulsionen in Hinblick auf ihren Zustand und die Herstellung untersucht. Die behandelten Emulsionen sollen als protektive topische Galeniken für von enzymatischer Degeneration gefährdete Wirkstoffe verwendet werden. Dies soll durch Verka...

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Bibliographic Details
Main Author: Beer, Sebastian
Contributors: Keusgen, Michael (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2016
Online Access:PDF Full Text
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This work deals with analysing multiple emulsions of the water-in-oil-in-water (W/O/W) type regarding their physical state and their production. The investigated emulsions are to be used as drug delivery systems, offering protection of sensitive drugs against enzymatic degradation. This is achieved by encapsulation of the drug inside of the multiple emulsion. For the application as a pharmaceutical product, the quality parameters stability, encapsulation efficiency and reproducability of the production have to be considered. In this work, the theoretical foundation and the required methods are developed aiming towards an application of the multiple emulsions as a pharmaceutical product. The physical properties of emulsions and thereby their produtcion are, apart from the materials used, governed by the droplet sizes and the disperse phase ratio. When analysing W/O/W emulsions, these parameters are prone to change, as water might migrate between the inner and the continuous water phase along existing pressure gradients. The theoretical relationship between the disperse phase ratio and the pressure gradient are established and analysed. The common analysis methods - rheology and static light scattering - are adapted to the emulsions of subject. In these analysis methods, the disperse phase ratio is one influential parameter next to other, not directly quantifyable parameters. To analyse the disperse phase content, a method based on confocal microscopy is developed which measures the disperse phase content directly. Using this method, the theoretical relationship is analysed. Via different production schemes and the subsequent analysis of the disperse phase content, the processes occuring during the production are identified. The combination of droplet size reduction and variable disperse phase ratios creates a positive feedback. Difficulties regarding the reproducability of the multiple emulsions can be explained by this self amplifying process. To account for this, an in-line measurement method (describing the state of the emulsion during the production) based on dielectric spectroscopy is developed and demonstrated. The quantified relationship between disperse phase content and the pressure gradient enables via the measurement of the disperse phase content the determination of the encapsulation efficiency. An evaluation of the sensitivity of the multiple emulsions against destabilising phenomena was conducted based on the developed relationship. The temperature dependance of the interfacial tensions leads towards the development of a stresstest to determine the stability of the emulsions against temperature variations. The scientific and methological foundations leading towards an application of the subject emulsions as a pharmaceutical product are developed in this work.