The feasibility of in-situ alloying of AISI 410L martensitic stainless steel with nitrogen during Nd-YAG laser cladding was investigated with the aim of achieving a nitrogen content of at least 0.08 wt% and fully martensitic microstructures in the final clad deposit. Two in-situ nitrogen alloying techniques were studied. In the first set of experiments, the absorption of nitrogen from nitrogen-rich gas atmospheres was studied. Laser cladding with commercially available AISI 410L powder was performed using nitrogen-rich shielding and carrier gas. A marginal increase in deposit nitrogen content was observed, with the clad deposit displaying low hardness and mostly ferritic microstructures. Poor nitrogen absorption from nitrogen-containing atmospheres during Nd-YAG laser cladding is generally attributed to the short thermal cycle and to suppression of plasma formation above the weld pool. In the remaining experiments, Si3N4 powder was investigated as an alternative source for nitrogen during cladding. The addition of Si3N4 to the AISI 410L powder feed resulted in clad microstructures consisted of columnar -ferrite grains with martensite on the grain boundaries, higher hardness and an increase in deposit nitrogen content (to a maximum of 0.064 wt% nitrogen). Higher nitrogen contents in the clad deposit, however, significantly increased the volume percentage porosity in the clad layer. This prompted an investigation into the feasibility of raising the nitrogen solubility of the alloy through additions of manganese and nickel to the powder feed. Thermodynamic modelling revealed that the addition of manganese to AISI 410L powder increases the nitrogen solubility limit due to its negative interaction parameter with nitrogen. The addition of up to 3.5 wt% manganese to AISI 410L powder containing Si3N4 significantly increased the nitrogen solubility in the deposit. A martensitic microstructure with 0.12 wt% nitrogen and a peak hardness of 410 HV was achieved without any adverse increase in porosity in the clad layer. The clad nitrogen content easily exceeded the minimum requirement of 0.08 wt%. High nickel concentrations in AISI 410L stainless steel expand the austenite phase field at the expense of -ferrite and alter the solidification mode from ferritic to austenitic-ferritic. The addition of up to 5.5 wt% nickel, or combinations of nickel and manganese, to the nitrogen-alloyed AISI 410L powder feed raised the deposit nitrogen content, but not to the same extent as those deposits alloyed with manganese only. Since more austenite is present on cooling in nickel-alloyed AISI 410L deposits, less nitrogen is rejected to the liquid phase on solidification, resulting in higher nitrogen contents and less porosity in the room temperature microstructures. The amount of dilution during single-track laser cladding is mainly influenced by the specific energy per unit mass delivered by the laser beam. The clad height is strongly influenced by the powder deposition rate, whereas the bead width is influenced by the wettability of the deposits during laser cladding. During multi-track cladding, the observed percentage porosity is a function of the aspect ratio of the individual beads making up the clad layer, the deposition rate and the clad height. High deposition rates result in thicker layers, increasing the distance that N2 gas bubbles have to travel to escape to the atmosphere, while a high aspect ratio favours interbead porosity. The results suggest that in-situ nitrogen alloying during laser cladding should preferably be performed at low deposition rates to ensure higher clad nitrogen contents and hardness, lower clad heights, less dilution and less porosity. / Dissertation (MEng)--University of Pretoria, 2016. / Materials Science and Metallurgical Engineering / MEng / Unrestricted

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...

Charles University Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Marie Šilhanová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title of diploma thesis: The influence of solubility and adsorption on plastic materials on transport experiments From transport experiments on cell culture models we get valuable information about transport mechanism of drugs in organism. In vitro experiments are conducted for example on Transwell type inserts. During the experiment it was discovered that the results are not homogeneous, and the quantity of a substance in the solution decreases apparently, the reason behind this is inadequate solubility of lipophilic substances or their adsorption on the surface of plastic materials used in the experiment. Due to these problems we experience significant bias. This thesis is focused on antivirotics that did not perform well during transport experiments. First, HPLC/MS methods were developed, and they were used for concentration measurement of samples containing individual antivirotics. The drugs were tested under wide range of conditions so possible changes in effects of adsorption on plastic surfaces and solubility of drugs could be observed. The substances were divided into groups based on...

Objectives Glyburide, an important drug for type 2 diabetes, has extremely poor aqueous solubility and resulting low bioavailability. This study describes the ability of hydroxybutenyl-β-cyclodextrin (HBenBCD) to form complexes with glyburide, with enhanced solubility and dissolution rate in vitro. Method Glyburide and glyburide-HBenBCD were evaluated in various test media known to simulate human gastrointestinal conditions in the fasted and fed states, respectively. Key findings At ~14 wt% drug load, in the presence of HBenBCD, an almost 400-fold increase in glyburide aqueous solubility was observed. In the presence of HBenBCD, glyburide solubility was also significantly improved in all physiologically relevant test media. Subsequent dissolution experiments confirmed the solubility study results; the dissolution rate and total amount of drug released were significantly increased. Conclusions Complexation with HBenBCD may be an effective way to increase the bioavailability of glyburide.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19020号 / 農博第2098号 / 新制||農||1030(附属図書館) / 学位論文||H27||N4902(農学部図書室) / 31971 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 加納 健司, 教授 宮川 恒, 教授 三上 文三 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

<p><br></p><p>The pharmaceutical industry depends on deeply understanding pharmaceutical excipients and active ingredients. The physicochemical properties must be sufficiently understood to create a safe and efficacious drug product. High-throughput methods have reduced the time and material required to measure many properties appropriately. However, some are more difficult to evaluate. One such property is solubility or the equilibrium dissolvable content of the material. Solubility is an essential factor in determining the bioavailability of an active ingredient and, therefore, directly impacts the effectiveness and marketability of the drug product.</p><p>Solubility can be a challenging, time-consuming, material-intensive property to measure correctly. Due to the challenge associated with determining experimental values, researchers have devoted a significant amount of time toward the accurate prediction of solubility values of drug-like compounds. This remains a difficult task as there are two hurdles to overcome: data quality and specificity of molecular descriptors. Large databases of reliable solubility values have become more readily available in recent years, lowering the first barrier to more accurate solubility predictions. The second hurdle has proven more challenging to overcome. Advances in artificial intelligence (AI) have provided opportunities for improvement in estimations. Expressly, the subsets of machine learning and neural networks have provided the ability to evaluate vast quantities of data with relative ease. The remaining barrier arises from appropriately selecting AI techniques with descriptors that accurately describe relevant features. Although many attempts have been made, no single set of descriptors with either data-driven approaches or <i>ab initio</i> methods has accurately predicted solubility.</p><p>The research within this dissertation focuses on an attempt to lower the second barrier to solubility prediction by starting with molecular features that are most important to solubility. By deriving molecular descriptors from the electronic properties on the surface of molecules, we obtain precise descriptions of the strength and locality of intermolecular interactions, critical factors in the extent of solubility. The novel molecular descriptors are readily integrated into a Deep-sets based Graph and Self-Attention Neural Network, which evaluates predictive performance. The findings of this research indicate significant improvement in predicting intrinsic solubility over other literature-reported methods.</p>

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23576号 / 工博第4931号 / 新制||工||1770(附属図書館) / 京都大学大学院工学研究科原子核工学専攻 / (主査)教授 佐々木 隆之, 教授 横峯 健彦, 准教授 小林 大志 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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There is considerable interest among food manufacturers to incorporate protein into food products in both developed and developing countries. Dairy proteins are excellent choices for many different applications, as they are known to have several nutritional and functional benefits. Membrane filtration techniques are often utilized as the preferred method of fractionation, due to the high throughput and continuous nature of the process. One such product produced from membrane filtration of skim milk is called milk protein concentrate. This product is valued for its high protein content, but it has historically exhibited poor solubility when reconstituted into water, which severely restricts the food applications for which it is suitable. There is some existing evidence that milk protein concentrates which contain elevated levels of sodium exhibit higher solubility upon reconstitution into water. The main objective of this thesis project was to demonstrate the effect of sodium chloride, added to diafiltration (DF) water utilized during the manufacturing process, on the solubility of milk protein concentrate. It was observed that the addition of sodium chloride into diafiltration water at levels of 50 mM, 100 mM, and 150 mM had a beneficial effect on the solubility of milk protein concentrate across a variety of reconstitution conditions. For example, when milk protein concentrate was mixed for 1 h on a stage mixer at 23 °C ± 1 °C, a significant increase (p < 0.001) in mean solubility was observed when at least 50 mM NaCl had been incorporated into DF water. The incorporation of 50 mM NaCl into DF water significantly increased (p < 0.001) the mean solubility of milk protein concentrate from 59.81 % to between 64.34 % and 71.78 %. The addition of 100 mM NaCl significantly increased (p < 0.001) the solubility to between 88.80 % and 96.24 %, and the addition of 150 mM NaCl significantly increased (p = 0.005) the solubility to between 92.79 % and 100 %. Minerals analysis of dry powders revealed a significant increase (p < 0.001) in levels of sodium. The addition of 50 mM NaCl into DF water was associated with a significant increase (p < 0.001) in powder Na content to between 2.48 mg/g and 7.44 mg/g. The addition of 100 mM NaCl into DF water was associated with a significant increase (p = 0.002) in powder Na content to between 5.80 mg /g and 10.75 mg/g, and the addition of 150 mM NaCl into DF water was associated with a significant increase (p = 0.001) in powder Na content to between 9.57 mg/g and 14.53 mg/g. A significant difference (p < 0.001) in magnesium level was also detected. Differences in calcium content were not found to be statistically significant (p = 0.016) at α = 0.01. Preliminary observations of milk protein concentrate upon reconstitution were made using a confocal laser scanning microscopy method. This method showed evidence of possible differences in powder particle rehydration and affinity for lipid association between powder particles manufactured at different treatment levels. As the level of NaCl incorporated into DF water increased, particle structures upon rehydration appeared more porous, and the incidence of lipid material that was not associated with powder particles appeared to increase. Overall, this study demonstrates the importance of sodium content in determining the solubility of milk protein concentrate.