Dokument

Summary:
Within this thesis, it was possible to set up a method of preparation that exhibits many of the desired characteristics. Up to the current point, the system includes the following possibilities: - preparation of hydrophilic microparticles of different polymers - no use of toxic substances is necessary - suitable cleaning and drying process for hydrophilic microparticles - particle stability at room temperature under air conditions for at least 11 months, depending on the formulation - encapsulation of hydrophilic compounds into hydrophobic nanoparticles - encapsulation of hydrophobic nanoparticles into hydrophilic microparticles - encapsulation of hydrophilic compounds into hydrophilic microparticles - surface modification of hydrophobic nanoparticles for targeting - preparation of porous dextran microparticles All used substances are not classified as ‘toxic’; however, at certain concentrations they are toxic to the human body. The lungs are a very sensitive organ and might react to some of these substances, even at low concentrations. Currently, there are no polymers approved for pulmonary drug delivery by EMA or FDA, but it is likely that especially biopolymers such as dextran do not show a severe impact on the lungs, if used. The organic solvents and stabilizers are more problematic. For a final formulation, they have to be minimized. For pentane, this should not be much of a problem, as it is very volatile and will not mix with the hydrophilic particles. Ethyl acetate also would not mix with the particles and should be possibly removed by freeze drying. Also, ethyl acetate is contained in, for example, wine, fruits and some kinds of nail polish. An ingestion and inhalation of smaller amounts is obviously without risk for a healthy person. Acetonitrile is more toxic than ethyl acetate, but not essential for the drying process. It has been used in this thesis, because its freezing point is at -45 °C, and it was therefore suitable for freeze drying from an organic solvent on a laboratory scale. For an industrial application, an exchange to ethanol and subsequent freeze drying would be more suitable and less toxic. The stabilizers, on the other hand, could be a major problem for pulmonary application, as they cannot be removed by freeze drying. Since they are very hydrophobic, it is not clear whether they dissolve in the alveolar lining fluid or not, but if they do, they have the potential to change its properties and affect the breathing ability. Some features of the system are only assumed and could not be proven within this thesis: - particle sizes prepared with multiple membrane cycles are suitable for lung deposition - particle sizes prepared with multiple membrane cycles are suitable for entering hair follicles These features require future work to prove or disprove them.

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