Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Mueller, M.
Impact of budesonide properties on biological actions in the lung
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2019. pp. 54
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fröhlich Eleonore
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- Abstract:
- Budesonide, a synthetic glucocorticoid, is a widely used drug for the long-term treatment of respiratory diseases such as bronchial asthma or chronic obstructive pulmonary disease (COPD). Its pulmonary application enhances a fast onset of action and by avoiding the first pass effect, smaller systemic plasma concentrations and less adverse effects can be beneficial for the patient in comparison to systemic application. The active pharmaceutical ingredient (API) has to be processed to a size of less than 5 μm in order to reach what will be referred to as “the deep lung” (the terminal bronchioles and alveoli). In this study, budesonide was modified by spray drying and jet milling, and the produced particles were compared in terms of size, shape and solid state, as well as their uptake by epithelial and macrophage cell lines and primary human macrophages and their permeability through a monolayer of epithelial cells. For determination of aerodynamic properties particles were bound to lactose carrier molecules (blended) and the detached particles were separated according to their size in the Next Generation Impactor (NGI). Dissolution of the particles in size < 5 μm was assessed by incubation in simulated lung fluid. Spray dried, predominantly amorphous budesonide particles showed smooth surfaces and were spherically shaped, whereas the jet milled, crystalline API had rough surfaces and was rod-like and rather irregular in shape. In all tested cell lines, the uptake and permeability of jet milled budesonide was lower than the respective parameters of the spray dried material. A slightly different dissolution pattern was determined, and there was a notable difference in the aerodynamic performance of the two particles. The fine particle fraction (FPF), the amount of API that reaches the NGI parts that represent the deep lung, was significantly higher for jet milled budesonide compared to the FPF of the blend with the spray dried API. Significantly higher uptake of the spray dried budesonide was seen only in human primary macrophages.