Dokument: Paediatric drug development for praziquantel
| Titel: | Paediatric drug development for praziquantel | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=45305 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20180327-141331-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Münster, Magdalena [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Gutachter] Prof. Dr. Kleinebudde, Peter [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The objective of this thesis was to identify, conduct and compare various taste masking strategies in the pharmaceutical development of liquid and solid oral dosage forms for paediatrics. Praziquantel (PZQ) was chosen as a suitable model compound with regard to its generally known aversive and bitter taste. Moreover, PZQ is currently used against schistosomiasis in humans and various worm infections in animals including difficult patient populations such as children and picky animals like cats. There is a high need for a taste masked and acceptable formulation as especially very young children cannot swallow the currently used tablets due to their large size and bitter taste. Based on the chemical and physical characteristics of PZQ appropriate taste masking techniques were chosen and applied. The focus was set on the complexation, encapsulation and embedding of PZQ in liquid or solid dosage forms to facilitate an efficient taste masking during oral uptake.
Within liquid formulations the taste masking efficiency of maltodextrins (MDs) was evaluated in comparison to cyclodextrins (CDs) in solution. As a prerequisite for the successful analysis of these multicomponent liquid systems, different non-human taste assessment tools were examined for PZQ. The electronic tongue and the rodent brief-access taste aversion (BATA) model were chosen as the most useful methods based on current literature. The evaluated sensors of the electronic tongue in this study were not applicable for PZQ due to the non-ionic characteristic and the low solubility of PZQ in water. None of the tested sensors provided conclusive responses for PZQ and hence for further evaluation of multicomponent systems. In contrast, the rats in the BATA model demonstrated a concentration-dependent sensitivity to the PZQ aversiveness, leading to an IC50 value of 0.06 mg/ml. During the experiment, a maximum concentration of 0.01 mg/ml of PZQ in water was identified as well tolerated with no significant difference to pure water. Based on these findings the taste masking efficiency of MDs and CDs were evaluated in the BATA model revealing the MD as efficient as both CDs for PZQ. In the view of a final dosage form MDs would be preferable over CDs due to various reasons such as excipient costs and safety. Within solid formulations mini-tablets (MTs) were chosen as the most suitable and flexible dosage form for the majority of patients including children. To efficiently inhibit the interaction of PZQ with the taste buds during oral uptake of the MTs, PZQ was encapsulated or embedded in a carrier system. First, via a solvent casting method various polymers were evaluated for the combined approach of a taste masking effect in simulated salivary fluid and a fast solubilization of PZQ in simulated gastric and intestinal media. Second, among various taste masking approaches, extrusion and spray-drying were applied for PZQ with a subsequent processing of the formulations to mini-tablets (MTs). Extrusion of PZQ with Eudragit® E PO and glyceryl monostearate enabled an exceptional delayed drug release in simulated salivary fluid and an increased solubility kinetic of the drug in simulated gastric and intestinal media in comparison to spray-dried formulations and physical mixtures. This was observed for powder formulations as well as for subsequent manufactured MTs. In conclusion, the developed ready-to-use MTs are superior to the solution with MD in terms of administration, stability, transport and use. They provide an easy ingestion including for patients with swallowing difficulties and a high flexibility regarding dosing. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 27.03.2018 | |||||||
| Dateien geändert am: | 27.03.2018 | |||||||
| Promotionsantrag am: | 22.12.2017 | |||||||
| Datum der Promotion: | 01.02.2018 |
