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Program-controlled freeze drying for the preparation of the drug-delivery system based on polysaccharide and hydrophobic molecules
Dufková, Michaela ; Kalina, Michal (referee) ; Enev, Vojtěch (advisor)
The lyophilization process favors the hydrophobic effect between the individual dextran chains. This hydrophobic effect allows hydrophobic drugs to settle and remain within the biopolymer. Due to hydrophobic effect, dextran can serve as a carrier for the distribution of hydrophobic drugs. The goal of this thesis was to prepare a carrier system based on native dextran using program-controlled freeze-drying. Hydrophobic drugs were modeled using the fluorescent probes pyrene and prodane. The effectiveness of promoting the hydrophobic effect was studied using infrared spectrometry, fluorescence spectrometry and scanning electron microscopy. Using ATR-FTIR spectrometry, a shift of the absorption band of thevalence vibration of the C–O bond in OH groups in alcohol was observed. Using fluorescence spectrometry, the emission polarity index was calculated for pyrene from the 1st and 3rd maximum fluorescence intensity, and for prodan, a shift of the maximum fluorescence intensity to lower wavelengths was observed. SEM images showed that during the lyophilization process, the dextran structure formed a dense network of fibers, indicating the presence of many sites with a higher content of hydrophobic domains. Positive results were obtained with these methods, which proved the positive effect of lyophilization on the formation of a hydrophobic effect between individual polysaccharide chains. The results may contribute to the development of carrier systems for hydrophobic drugs.
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Program-controlled freeze drying for the preparation of the delivery system based on hyaluronan and real drugs
Řihák, Marek ; Sedláček, Petr (referee) ; Enev, Vojtěch (advisor)
The aim of this thesis was to prepare native hyaluronan-based carrier systems using the lyophilisation as a suitable method to ensure an interaction between certain drugs and the polymeric structure which would lead to an increased solubility of hydrophobic drugs. For the preparation of such a system the tert-butyl alcohol was used as a co-solvent with the ability to support hydrophobic effect between the drug and a hydrophobic domain of hyaluronan. Since all polar domains of hyaluronan are located in the equatorial position, the axial position is occupied by hydrogens and therefore the molecule gains the amphiphilic character. Previous studies have confirmed that freeze-drying is a useful method for a carrier system preparation. However, this study focuses on the preparation of such systems with samples of real drugs, which were previously replaced by fluorescence sondes. Since all drug samples have good fluorescence characteristics, the fluorescence spectroscopy was used as the main method to determine the success of the preparation. Other methods included a thermogravimetric analysis and the infrared spectroscopy with Fourier transformation. All the mentioned methods have confirmed that lyophilisation is a useful method for the preparation of the carrier systems with real drugs. Great results have been achieved in the terms of the solubility of freeze-dried systems. In the last step, the co-solvent residues were determined by head-space solid phase microextraction. This method also provided some valuable information and confirmed that tert-butyl alcohol could be found in the lyophilised systems only on very low levels.
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