Magister Pharmaceuticae - MPharm / Many active pharmaceutical ingredients (APIs) have poor physicochemical properties such as solubility, dissolution and chemical stability. Several strategies are used to enhance and improve these properties of the API. Co-crystallization and polymorphism studies are possible strategy used in pre-formulation studies to optimize these properties of the drug without modifying its pharmacological effect. The purpose of this research was to investigate the polymorphism and co-crystallization effects of the penicillin-type antibiotic, amoxicillin tri-hydrate. Several techniques such as: slow evaporation, slow cooling, vapour diffusion, sublimation, grinding and solvent assisted grinding was employed. In producing co-crystals, the API was non-covalently bound to selected co-formers such as: saccharin, nicotinamide, salicylic acid, L-tartaric acid, D-tartaric acid, L-aspartic acid, stearic acid, benzoic anhydride, oxalic acid di-hydrate, cinnamic acid, succinic acid and citric acid monohydrate. Nine co-crystals of amoxicillin tri-hydrate had been formed. Differential scanning calorimetry (DSC), hot stage microscopy (HSM) and thermal gravimetric analysis (TGA) was conducted to analyse the thermal behaviour of the co-crystals. Powder X-ray diffraction (PXRD) and spectroscopic techniques [infra-red (FTIR) and H1-nuclear magnetic resonance (H1MNR)] were employed for screening of the co-crystal forms. Furthermore, dissolution testing was conducted to investigate the application of the newly derivatised forms.

Orientador: Ines Joekes / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-07T18:47:07Z (GMT). No. of bitstreams: 1 Valentim_IaraBarros_D.pdf: 957586 bytes, checksum: 1311d37d4e3ea52a252e10626fcd04c3 (MD5) Previous issue date: 2006 / Doutorado / Físico-Química / Doutor em Ciências

Freshwater ecosystems have been recognized as important components of the global carbon cycle, and the flux of organic matter (OM) from freshwater to marine environments can significantly affect estuarine and coastal productivity. The focus of this study was the assessment of carbon dynamics in two aquatic environments, namely the Florida Everglades and small prairie streams in Kansas, with the aim of characterizing the biogeochemistry of OM. In the Everglades, particulate OM (POM) is mostly found as a layer of flocculent material (“floc”). While floc is believed to be the main energy source driving trophic dynamics in this oligotrophic wetland, not much is known about its biogeochemistry. The objective of this study was to determine the origin/sources of OM in floc using biomarkers and pigment-based chemotaxonomy to assess specific biomass contributions to this material, on a spatial (freshwater marshes vs. mangrove fringe) and seasonal (wet vs. dry) scales. It was found that floc OM is derived from the local vegetation (mainly algal components and macrophyte litter) and its composition is controlled by seasonal drivers of hydrology and local biomass productivity. Photo-reactivity experiments showed that light exposure on floc resulted in photo-dissolution of POC with the generation of significant amounts of both dissolved OM (DOM) and nutrients (N & P), potentially influencing nutrient dynamics in this ecosystem. The bio-reactivity experiments determined as the amount and rate of CO2 evolution during incubation were found to vary on seasonal and spatial scales and were highly influenced by phosphorus limitation. Not much is known on OM dynamics in small headwater streams. The objective of this study was to determine carbon dynamics in sediments from intermittent prairie streams, characterized by different vegetation cover for their watershed (C4 grasses) vs. riparian zone (C3 plants). In this study sedimentary OM was characterized using a biomarker and compound specific carbon stable isotope approach. It was found that the biomarker composition of these sediments is dominated by higher plant inputs from the riparian zone, although inputs from adjacent prairie grasses were also apparent. Conflicting to some extent with the River Continuum Concept, sediments of the upper reaches contained more degraded OM, while the lower reaches were enriched in fresh material deriving from higher plants and plankton sources as a result of hydrological regimes and particle sorting.

Release of uranium from Na-autunite, an artificial mineral created as a result of polyphosphate injection in the subsurface at the DOE Hanford Site, takes place during slow dissolution of the mineral structure. Stability information of the uranyl-phosphate phases is limited to conditions involving pH, temperature, and a few aqueous organic materials. The carbonate ion, which creates very strong complexes with uranium, is the predominant ion in the groundwater composition. The polyphosphate technology with the formation of autunite was identified as the most feasible remediation strategy to sequester uranium in contaminated groundwater and soil in situ. The objectives of the experimental work were (i) to quantify the effect of bicarbonate on the stability of synthetic sodium meta-autunite created as a result of uranium stabilization through polyphosphate injection, (ii) calculate the kinetic rate law parameters of the uranium release from Na-autunite during dissolution, and (iii) to compare the process parameters with those obtained for natural calcium meta-autunite. Experiments were conducted using SPTF apparatus, which consists of syringe pumps for controlling flow rate, Teflon reactors and a heating/cooling system. 0.25 grams of synthetic Na-autunite was placed in the reactor and buffer solutions with varying bicarbonate concentrations (0.0005 to 0.003 M) at different pH (6 - 11) were pumped through the reactors. Experiments were conducted at four different temperatures in the range of 5 - 60oC. It was concluded that the rate of release of uranium from synthetic Na-autunite is directly correlated to the bicarbonate concentration. The rate of release of uranium increased from 1.90 x 10-12 at pH 6 to 2.64 x 10-10 (mol m-2 s-1) at pH 11 at 23oC over the bicarbonate concentration range tested. The activation energy values were invariant with the change in the bicarbonate concentration; however, pH is shown to influence the activation energy values. Uranyl hydroxides and uranyl carbonates complexes helped accelerate the dissolution of autunite mineral.

Nanoscience and nanotechnology offer potential routes towards addressing critical issues such as clean and sustainable energy, environmental protection and human health. Specifically, metal and metal oxide nanomaterials are found in a wide range of applications and therefore hold a greater potential of possible release into the environment or for the human to be exposed. Understanding the aqueous phase behavior of metal and metal oxide nanomaterials is a key factor in the safe design of these materials because their interactions with living systems are always mediated through the aqueous phase. Broadly the transformations in the aqueous phase can be classified as dissolution, aggregation and adsorption which are dependent and linked processes to one another. The complexity of these processes at the liquid-solid interface has therefore been one of the grand challenges that has persisted since the beginning of nanotechnology. Although classical models provide guidance for understanding dissolution and aggregation of nanoparticles in water, there are many uncertainties associated with the recent findings. This is often due to a lack of fundamental knowledge of the surface structure and surface energetics for very small particles. Therefore currently the environmental health and safety studies related to nanomaterials are more focused on understanding the surface chemistry that governs the overall processes in the liquid-solid interfacial region at the molecular level. The metal based nanomaterials focused on in this dissertation include TiO2, ZnO, Cu and CuO. These are among the most heavily used in a number of applications ranging from uses in the construction industry to cosmetic formulation. Therefore they are produced in large scale and have been detected in the environment. There is debate within the scientific community related to their safety as a result of the lack of understanding on the surface interactions that arise from the detailed nature of the surfaces. Specifically, the interactions of these metal and metal oxide nanoparticles with environmental and biological ligands in the solutions have demonstrated dramatic alterations in their aqueous phase behavior in terms of dissolution and aggregation. Dissolution and aggregation are among the determining factors of nanoparticle uptake and toxicity. Furthermore, solution conditions such as ionic strength and pH can act as controlling parameters for surface ligand adsorption while adsorbed ligands themselves undergo surface induced structural and conformational changes. Because, nanomaterials in both the environment and in biological systems are subjected to a wide range of matrix conditions they are in fact dynamic and not static entities. Thus monitoring and tracking these nanomaterials in real systems can be extremely challenging which requires a thorough understanding of the surface chemistry governing their transformations. The work presented in this dissertation attempts to bridge the gap between the dynamic processing of these nanomaterials, the details of the molecular level processes that occur at the liquid-solid interfacial region and potential environmental and biological interactions. Extensive nanomaterial characterization is an integral part of these investigations and all the materials presented here are thoroughly analyzed for particle size, shape, surface area, bulk and surface compositions. Detailed spectroscopic analysis was used to acquire molecular information of the processes in the liquid-solid interfacial region and the outcomes are linked with the macroscopic analysis with the aid of dynamic and static light scattering techniques. Furthermore, emphasis is given to the size dependent behavior and theoretical modeling is adapted giving careful consideration to the details of the physicochemical characterization and molecular information unique to the nanomaterials.

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: Consultants: Assoc. Prof. PharmDr. Zdeňka Šklubalová, Ph.D. Mgr. Jana Brokešová, Mgr. Daniel Pěček Student: Miroslav Ouzký Title of Thesis: Study of excipientsʼ influence on the drug dissolution from tablets The aim of this work was to study the influence of excipients on the dissolution of the high-dose active substance from tablets. The tablets were compressed from the granules prepared by wet-granulation method. 11 batches of tablets which contained two different fillers: either lactose or microcrystalline cellulose, respectively; and extragranularly added disintegrant: either croscarmellose or crospovidone, respectively, in three concentration levels of 2 %, 3,7 % or 5,4 % were prepared. Tablets were packed into aluminium/PVC blisters. The paddle dissolution test was used to determine the release of the active substance into phospate buffer pH 7,2 at the time of preparation (time 0) and at the time points 1.5, 3 and 6 months of stability assay at 40 řC and 75 % relative air humidity. The results show that the drug release from tablets containing microcrystalline celulose was generally faster than from those containing lactose. The same was true for tablets to which croscarmellose was...

Dissolution and termination of foundation focusing on its winding up Abstract This diploma thesis titled Dissolution and termination of foundation focusing on its winding up is divided into five parts. The main aim of this thesis was to analyze the problematics of dissolution and termination of foundations which is an area quite insufficiently explored and discussed by the professional legal public. The other aim of this thesis was to analyse and evaluate recent Czech legislation of foundation area. Opening part of this thesis is dedicated to the general concept of a foundation as a legal person focusing on the conceptual elements of this legal entity; e. g. its establishment, creation, property, possibility to finance itself through some business activities, compulsory bodies and its activity. The attention was also focused on its historical perspectives and evolution, on the legislation of foundations and also on their current position in society and anticipated future. Second part is dealing with the liquidation process itself as comprehensive and complex procedure following after process of dissolution. Chapters of this part explain e. g. the purpose of liquidation process, the role of liquidator and each step of this procedure. Key part of this thesis is part number three. Main aim of this part is to...

Magister Pharmaceuticae - MPharm / Malaria remains one of the top mortality causes in the sub-Saharan African region, especially among pregnant women and infants. Despite several measures being implemented within the affected areas such as the use of treated mosquito nets, sulfadoxine and pyrimethamine (SULPYR) as an intermittent preventive treatment (IPTp-SP) is still considered the standard prophylactic regimen for pregnant women. Recently, the WHO increased the regimen of IPTp- SP from three to four doses on a monthly interval, this recommendation poses a potential risk of toxicity and resistance to the drugs. An improvement towards this challenge is under clinical trial and consists of the inclusion of azithromycin (AZI), a macrolide antibiotic, to the current IPTp-SP treatment regimen. This will not only aid in the prophylaxis of malaria in pregnant women but will also assist in other pregnancy related infections. All three these drugs exhibit poor aqueous solubility; requiring high concentrations for oral administration to achieve therapeutic plasma concentrations. / 2024

Czechoslovakia, as a common state of Czechs and Slovaks, dissolved after 74 years of existence. The thesis is conducted as a historical analysis whose aim to analyse the causes of the dissolution of Czechoslovakia and to identify their historical origins. The theoretical framework which accompanies the analytical part is based on Gellner's nationalism theory, Deutsch’s theory of social communication and theoretical conditions regarding the coexistence of nations in multinational states. The thesis demonstrates that the Czech-Slovak convergence, created by the utilization of the Czech language in Slovakia, geopolitical closeness and belonging to the same cultural circle, was not sufficient enough to overcome the administrative borders which contributed to the Czech-Slovak bipolarity. The analysis shows that even though the dissolution was an issue of political elites, the partition was predominantly caused by the Czech-Slovak dualism which was an after-effect of asynchronous historical development in two different state formations. The heterogeneous historical development resulted in retardation of the Slovak nationalism and unequal positions of the Czechs and Slovaks during Czechoslovakia. This was reflected in different perspectives on the common state and consequent differences in political cultures of Czechs and Slovaks.

Two soils were used in this soil column study. Yolo loam soil a non- c al c areous, non-gypsiferous soil from central California and Vernal soil a calcareous soil from eastern Utah. Initial studies were conducted where the solubilities of pure CaC0 3 and CaS0 4 ' 2H 2 0 were determined in the presence of Logan river water, a KCl solution (2.8 mmhos/cm) and a K 2 S0 4 solution (Z. 7 mmhos/cm). Gypsum was more soluble in the KCl solution than in the K Z S0 4 solution. The solubility product of both gypsum and lime were determined from the analytical data. The formation of CaS0 4 0 and caco 3 0 ion pairs were cons idered to be the most important complex ions pres ent. A reasonable agreement was observed between the theoretical values of K and the ca lculated K sp sp Essentially the same results were obtained when these waters were used in leaching the columns of Yolo and Vernal soil columns The solubility of gypsUJn was greatest usmg the KCl leaching' solution and least using the K 2504 leaching solution. Logan river water gave intermediate values. Calcium carbonate was most soluble in the K 2504 leaching solution and les s in the KCl solution. It was found that measuring the ci+ concentration in the effluent was a more reliable index to steady state condition than using an electrical conductivity lneasurement. Unsaturated flow removed more salt per unit volume of effluent than saturated flow. The relative area method was used to analyze the effluent under saturated moisture flow. 2+ It was found that a certain amount of Ca derived from gypsum dissolution precipitated in the column as CaC0 3 . This amount 2+ , was greater than 15% of the Ca dlssolved from gypsum.