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The study of polymorphism and optimization of active pharmaceutical ingredients crystallisation
Novák, David ; Ing.Ladislav Cvak, Ph.D. (referee) ; Ing.Roman Gabriel (advisor)
Active pharmaceutical ingredients (APIs) are frequently delivered to the patient in the solid-state as part of an approved dosage form (tablets, capsules, etc.). Understanding and controlling the solid-state chemistry of APIs is therefore an important aspect of the drug development process. APIs can exist in a variety of distinct solid forms, including polymorphs, solvates, hydrates, co-crystals and amorphous solids. Each form displays unique physicochemical properties that can profoundly influence the bioavailability, manufacturability, stability and other performance characteristics of the drug. Most APIs are purified and isolated by crystallisation from an appropriate solvent during the final step in synthetic process. The main objective of a crystallisation process is to produce crystals with desired properties such as particle size distribution (PSD), shape and purity. All pharmaceutical dosage forms must be produced in uniform units, and good content of uniformity is only possible when the size of the active component is carefully controlled. For on-line control of crystallisations of Quetiapine Fumarate to achieve desired PSD and no changed physicochemical purity was used the Lasentec Focus Beam Reflectance Measurement (FBRM) system.
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Phosphate binders
Kalina, Lukáš ; Ptáček, Petr (referee) ; Šoukal, František (advisor)
The work deals with the preparation and study of polyphosphate composites. Aluminum phosphates provide some unusual properties like high-heat resistance in terms of inorganic binders. The addition of chromium in the form of Cr2O3 or directly the bond with the aluminum-chromium-phosphate can improve the properties of this binder. Highly viscous Al2Cr(H2PO4)9 and Al3Cr(H2PO4)12 binders were prepared by dissolving Al(OH)3 and CrO3 in 85% phosphoric acid, and mixed with Al2O3 and Cr2O3 fillers. The composites were cured in the furnace at 150 °C for 24 h under pressure of 10 MPa. During the annealing at temperatures up to 1 500 °C changes in chemical structure of the cured composites were observed, leading to the understanding of the creation of crystalline phases and their eventual changes. The characterization of binders was mainly based on FT-IR, EDAX, TG-DTA and optical microscopy analyses.
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Plastic materials and their treatment
Kopečný, Aleš ; Zemčík, Oskar (referee) ; Osička, Karel (advisor)
This research the basic empirical knowledge about the processing of plastic materials. The following are analyzes of the nature of plastic materials and analysis of the use of these materials in the engineering industry. This paper deals with the technological methods of processing plastics. Specifically, it is done as a summary of information about the technologies needed for the production of molds for plastics. Key words
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Structural studies of mutant variants haloalkanedehalogenase DhaA106
MALCHER, Pavel
The aim of the thesis was to compare the haloalkane dehalogenase DhaA106 with other studied protein mutant variants. For diffraction analysis, it was necessary to growappropriate crystals of DhaA106 protein. Crystallization experiments were performed by standard sitting drop method. Obtained rod crystals were used for diffraction analysis. During diffraction measurement completeset of 500 diffraction images were obtained, from which the electron density map was formed and the spatial model of the molecular structure of DhaA106 dehalogenase was created. Alternative conformation of amino acids, water molecules, parts of precipitating solution and chloride ion inthe active sitewere subsequently added into the model structure. The final structure of the moleculewas refined and validated. Subsequently, the amino acids pentade in the active site and whole protein structure were analyzed . Values of validation and refining and interatomic distances in the active site were compared with several variants mutant dehalogenase DhaA, as well as the precipitating solutions used for crystallization and diffraction data collection. In the last step of the work interactions of the selected substrate with the protein surface in the vicinity of the tunnel connecting the active site of the surfacewere studied. Mentioned interaction study was based on the principle of combination of the Monte-Carlo methods with protein structure prediction algorithms.
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Structure-modelling studies of the haloalkane dehalogenase LinB
ŘEŽÁBEK, Josef
The main aim of this bachelor thesis was structure-dynamics study of LinB86 mutant variant protein isolated from the soil bacterium Sphingobium japonicum UT26. Standard and advanced protein crystallization techniques, basis of solving protein structures from diffraction data and study of enzyme structure and dynamics with the use of standard SW for molecular modelling were applied.
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Biodegradation environmental pollutans - characterization of mutant haloalkan dehalogenase DhaA31 of Rhodococcus rhodochrous NCIMB 13064
MALCHER, Pavel
The project was focused on using of protein crystallography practically and mainly on preparation of crystals of model protein Thermolysin and haloalkan dehalogenase mutant variant DhaA31 with the use of standard and advanced crystallization methods. Later the DhaA31 structure was solved and graphically visualized using the molecular modeling programs as well as the structure of Thermolysin. Obtaining the crystals of both studied proteins and description of the DhaA31 structure, active site and dehalogenation reaction were results of the project. DhaA31 mutant variant was prepared to increase the catalytic reaction during degradation of halogenated compounds such as 1,2,3-trichloropropane (TCP) from water sources.
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Kinetic behavior of the NAD(P)H:Quinone oxidoreductase WrbA from Escherichia coli.
KISHKO, Iryna
This Ph.D. thesis addresses the structure-function relationship of the multimeric oxidoreductase WrbA with the principal aim being the explanation of the unusual kinetics of this enzyme in molecular terms, and thus getting an insight about its physiological role in bacteria. WrbA is a multimeric enzyme with FMN as a co-factor, catalyzing the oxidation of NADH by a two electrons transfer. Structure and function analysis of WrbA places this enzyme between bacterial flavodoxins and eukaryotic oxidoreductases in terms of its evolutionary relationship. The kinetic activity of WrbA was studied under varying conditions such as temperature, pH etc, and its kinetic mechanism was evaluated from parameters KM and Vmax and confirmed by product inhibition pattern experiments. Crystallization and proteolytic experiments also underpin the functional importance of the multimeric nature of WrbA and aid the understanding of the physiological role of this enzyme in molecular terms.
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