Dokument: Development of a novel composite dosage form for oromucosal administration of locally and systemically active drugs
| Titel: | Development of a novel composite dosage form for oromucosal administration of locally and systemically active drugs | |||||||
| Weiterer Titel: | Entwicklung einer oromukosalen Composite-Darreichungsform für die oromukosale Anwendung von lokal und systemisch wirksamen Arzneistoffen | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=59160 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20220329-101602-2 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Kottke, Dina [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Gutachter] Prof. Dr. Seidlitz, Anne [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Within the present thesis, the development of a combined dosage form of already established dosage forms with the aims of either local, or systemic controlled efficacy of drugs administered to the oral cavity is described.
Initially, two manufacturing methods were investigated (direct incorporation method / adhesive method) for the manufacturing of the composite dosage form consisting of a bilayer mucoadhesive film and a solid matrix, in the form of a minitablet. The application of a shielding layer should ensure unidirectional release towards the oral mucosa to counteract uncontrolled swallowing of the drug. However, the adhesive method was found to be generally more suitable in terms of robustness, manual handling and lower drug migration within the dosage form. In terms of release behavior, differences could be identified but were within the specifications of Ph. Eur. A suitable formulation of the composite dosage form was developed for the incorporation of the locally active drug substance, lidocaine hydrochloride. The composite was shown to exhibit comparable ex-vivo permeations compared to a commercially available gel and higher permeation compared to in-house prepared mucoadhesive films. LC-MS/MS was used to provide reliable detection of small amounts of drug substance. Even though penetration would be better than systemic uptake for local efficacy of lidocaine hydrochloride, it was shown that the composite was not inferior to the semi-solid formulation. It could be shown that a controlled drug application was achieved by the composite dosage form, whereby the risk of inadvertent and fully swallowed as well as uncontrolled absorbed drug amount may be considerably minimized. A coaxial fluorescence detector based on a liquid core waveguide was developed and coupled to an HPLC for fast and reliable analysis. The system was validated according to bioanalytical guidelines (ICH Q2 and EMA). Thus, a tenfold increase in sensitivity was achieved in the quantification of desmopressin compared to previous data. This enabled the detection of clinically relevant doses of desmopressin. Subsequently, the applicability for ex-vivo permeation studies could be proven. Finally, the composite dosage form should be used to enable desmopressin oromucosal permeation. Minitablets were prepared as a solid matrix, which contained a precise dose of 200 µg desmopressin acetate, showing fast disintegration as well as immediate drug release properties. To produce minitablets which fulfill the requirements of the Ph. Eur. 2.9.40, a two-step granulation process and the addition of a loss supplement was necessary. Moreover, reliable determination of desmopressin delivery was achieved at a clinically relevant application dose and time. The present work has provided a new option to make locally and systemically active drugs available via the oral mucosa with increased precision and dosing accuracy compared to commercially available formulations such as gels. The main advantage is that no adhesive components need to be incorporated within the drug reservoir, thus the solid matrix of a minitablet, which can inevitably have a slowing effect on release and also on permeation due to swelling, for example. The two-layered structure of the composite MBF also enables unidirectional release towards the oral mucosa. This contributes to an improved drug safety, which is an aspect that should not be neglected, especially in infants and children. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 29.03.2022 | |||||||
| Dateien geändert am: | 29.03.2022 | |||||||
| Promotionsantrag am: | 21.11.2021 | |||||||
| Datum der Promotion: | 01.03.2022 |
