Metal-based nanoparticles (MNPs) are becoming increasingly common in commercial products. Release of these materials into the environment raises concerns about the potential risks they pose to aquatic life. Predicting these risks requires an understanding of MNPs' chemical transformations. In this study, arrays of immobilized MNPs fabricated by nanosphere lithography (NSL) were used to investigate environmental transformations of MNPs. Specifically, sulfidation of silver nanoparticles (Ag NPs) and dissolution of copper-based nanoparticles (Cu NPs) were investigated. Atomic force microscopy (AFM) and transmission electron microscopy were the primary analytical techniques for these investigations. Because the MNPs were immobilized on a solid surface, the samples were field deployable, environmentally relevant metal concentrations were maintained, and the confounding influence of MNP aggregation was eliminated. Ag NP samples were deployed in a full-scale wastewater treatment plant. Sulfidation occurred almost exclusively in anaerobic zones of the WWTP, where the initial sulfidation rate was 11-14 nm of Ag converted to Ag2S per day. Conversion to Ag2S was complete within 7-10 d. Dissolution rates of Cu-based NPs were measured in situ over a range of pH by flow-cell AFM. Based on the measured rates, CuO/Cu(OH)2 NPs dissolve completely within a matter of hours at any pH, metallic Cu NPs persist for a few hours to days, and CuxS NPs do not dissolve significantly over the time scales studied. Field deployment of samples in a freshwater stream confirmed these conclusions for a natural aquatic system. This research demonstrates that environmental transformations of MNPs will be a key factor in determining the ultimate form and concentration of NPs that aquatic organisms will be exposed to. / Ph. D.

The environmental fate and transport of engineered nanomaterials have been broadly investigated and evaluated in many published studies. Silver nanoparticles (AgNPs) represent one of the most widely manufactured nanomaterials. They are currently being incorporated into a wide range of consumer products due to their purported antimicrobial properties. However, either the AgNPs themselves or dissolved Ag+ ions has a significant potential for the environmental release. The safety issues for nanoparticles are continuously being tested because of their potential danger to the environment and human health. Studies have explored the toxicity of AgNPs to a variety of organisms and have shown such toxicity is primarily driven by Ag+ ion release. Dissolution of nanoparticles is an important process that alters their properties and is a critical step in determining their safety. Therefore, studying nanoparticles' dissolution can help in the current move towards safer design and application of nanoparticles. This research endeavor sought to acquire comprehensive kinetic data of AgNP dissolution to aid in the development of quantitative risk assessments of AgNP fate. To evaluate the dissolution process in the absence of nanoparticle aggregation, AgNP arrays were produced on glass substrates using nanosphere lithography (NSL). Changes in the size and shape of the prepared AgNP arrays were monitored during the dissolution process by atomic force microscopy (AFM). The dissolution of AgNP is affected by both internal and external factors. First, surface coating effects were investigated by using three different coating agents (BSA, PEG1000, and PEG5000). Capping agent effects nanoparticle transformation rate by blocking reactants from the nanoparticle surface. Coatings prevented dissolution to different extents due to the various way they were attached to the AgNP surface. Evidence for the existence of bonds between the coating agents and the AgNPs was obtained by surface enhanced Raman spectroscopy. Moreover, to study the size effects on AgNP dissolution, small, medium, and large sized AgNPs were used. The surrounding medium and temperature were the two variables that were included in the size effects study. Relationships were established between medium concentration and dissolution rate for three different sized AgNP samples. By using the Arrhenius equation to plot the reaction constant vs. reaction temperature, the activation energy of AgNPs of different sizes were obtained and compared. / Doctor of Philosophy / Nanomaterials, defined as materials with at least one characteristic dimension less than 100 nm, often have useful attributes that are distinct from the bulk material. The novel physical, chemical, and biological properties enable the promising applications in various manufacturing industry. Silver nanoparticles (AgNPs) represent one of the most widely manufactured nanomaterials and has been used as the antimicrobial agent in a wide range of consumer products. However, either the AgNPs themselves or dissolved Ag+ ions has a significant potential for the environmental release. The environmental fate and transport of AgNPs drawn considerable attentions because of the potential danger to environment and human health. Dissolution of nanoparticles is an important process that alters their properties and is a critical step in determining their safety. Ag+ ions migrate from the nanoparticle surface to the bulk solution when an AgNP dissolves. Studying nanoparticles' dissolution can help in the current move towards safer design and application of nanoparticles. This research aimed to acquire comprehensive kinetic data of AgNP dissolution to aid in the development of quantitative risk assessments of AgNP fate. AgNP arrays were produced on glass substrates using nanosphere lithography (NSL) and changes in the size and shape during the dissolution process were monitored by atomic force microscopy (AFM). First, surface coating effects were investigated by using three different coating agents. Coatings prevented dissolution to different extents due to the various way they were attached to the AgNP surface. Moreover, small, medium, and large sized AgNPs were used to study the size effects on AgNP dissolution. The surrounding medium concentration and temperature were the two variables that were included in the size effects study.

This dissertation presents the first reported identification and analyses of the phase relations in the YBa2Cu3O7-x (YBCO)-SiO2 system at elevated temperatures. In this regard, a rigorous characterization study of the reaction phases within YBCO glass fibers, heat-treated YBCO+SiO2 pellets, rapid thermally annealed YBCO+SiO2 rods and rapid thermally annealed YBCO powder inside a fused silica tube is provided. These analyses are based on a vast set of generated novel results obtained using energy dispersive spectroscopy analyses on an environmental scanning electron microscope, X-Ray diffraction analyses, Raman spectroscopy, X-ray photoelectron spectroscopy analyses and a cross-polarized light study. First, original drawings of YBCO into glass fibers using the molten-core approach on a fiber draw tower in air and oxygen atmospheres are presented and analyzed. The performed analyses reveal the occurrence of reactions between the YBCO core and the silica cladding in as-drawn fibers as well as after additional heat-treatments. A detailed analysis and characterization of the occurring dissolution and diffusion based reaction processes is, then, provided along with the identification of the arising phase separation. Moreover, in order to analyze drawing YBCO glass fibers at lower temperatures, the use of borosilicate as the preform material is also investigated. This varied set of experiments and associated analyses reveal that the as-drawn YBCO fibers contain an amorphous core and that cuprite (Cu2O) is the first phase to crystallize out of the amorphous silicate matrix upon heat-treatment. Furthermore, the obtained results demonstrate the dissolution of the fused silica cladding into Si4+ and O2- ions and their subsequent diffusion into the molten YBCO core, leading to phase separation due to an occurring miscibility gap in the YBCO-SiO2 system as well as to silicate formation and amorphization of the YBCO core. This, as a result, prohibits the formation of the superconductive YBCO (Y-123) phase upon annealing. In addition, heat-treatment analyses show that higher temperatures or prolonged dwelling times at lower temperatures lead to the formation of barium copper and yttrium barium silicates. The analysis focusing on the use of borosilicate as the preform material reveals that drawing at lower temperatures reduces the dissolution and diffusion based reactions, but does not prevent them. Furthermore, the analysis on YBCO glass fibers with a fused silica cladding drawn in oxygen atmosphere shows that a higher oxygen content increases the dissolution of the fused silica cladding into its ions and their subsequent diffusion into the molten YBCO core. In addition, the performed heat-treatments on YBCO+SiO2 pellets in air and oxygen atmospheres demonstrate the gradual decomposition of the Y-123 phase with an increase in SiO2 content. Moreover, the rapid thermal annealing experiments with a subsequent quenching step on YBCO+SiO2 rods and on YBCO powder inserted inside a fused silica tube show the decomposition of the Y-123 phase and the formation of phases similar to the phases obtained in the YBCO glass fiber study, thus corroborating the results thereof. In summary, this dissertation enables the determination of the phase relations and reaction processes within the YBCO-SiO2 system, the identification of the direct effects of the silicon content on the Y-123 phase decomposition, as well as a rigorous characterization of the dissolution and diffusion based reactions within the YBCO-SiO2 glass-clad fiber system. The generated results and drawn conclusions build a fundamental understanding of phase relations in the YBCO-SiO2 system, which enables a definite assessment of the feasibility of manufacturing long-scale purely superconductive YBCO glass fibers using the molten-core approach and introduces advanced contributions to general glass-clad fiber systems manufactured using this method. / Doctor of Philosophy / This dissertation provides the first reported identification and analysis of the phase relations in the YBa2Cu3O7-x (YBCO)-SiO2 system at high temperatures. In this regard, a thorough characterization study of the reaction phases within YBCO glass fibers drawn using the molten-core approach on a fiber draw tower is provided. In addition, heat-treatment analyses considering YBCO+SiO2 pellets, rapid thermally annealed YBCO+SiO2 rods and rapid thermally annealed YBCO powder inside a fused silica tube are performed to gain further fundamental insights. The performed analyses are based on a wide set of characterization methods including energy dispersive spectroscopy on an environmental scanning electron microscope, X-Ray diffraction analyses, Raman spectroscopy, X-ray photoelectron spectroscopy and a cross-polarized light study. Our experimental results and performed analyses identify the phase relations and reaction processes within the YBCO-SiO2 system at elevated temperatures, demonstrate the direct effects of the silicon content on the superconductive YBCO phase decomposition, enable drawing definite conclusions regarding the feasibility of manufacturing long-scale purely superconductive YBCO glass fibers using the molten-core approach, and, characterize the dissolution and diffusion based reactions occurring within the YBCO-SiO2 glass-clad fiber system. In a nutshell, this dissertation provides a fundamental understanding of phase relations in the YBCO-SiO2 glass-clad system as well as key insights covering general glass-clad fibers drawn using the molten-core approach, paving the way for improved glass-clad fiber manufacturing using this method.

[pt] Muitos contaminantes orgânicos, incluindo derivados do petróleo, como por exemplo a gasolina, têm baixa solubilidade em água e migram na subsuperfície como uma fase separada da água sendo referidos como NAPLs (non aqueous liquid phases). Em seu processo de migração na subsuperficie os NAPLs deixam para trás segmentos de líquidos disconectados na forma de gânglios ou lentes que constituem a fase residual do contaminante. A presença do contaminante residual constitui-se numa das maiores dificuldades para a implementação de uma técnica adequada de limpeza ou recuperação de locais contaminados, uma vez que tais contaminantes representam uma fonte lenta e continua de contaminação de solos e água subterrânea, especialmente por sua dissolução na água. Nesta tese, estudou-se o efeito do etanol na dissolução de gasolina residual. Tal estudo foi motivado pela necessidade de se obter um melhor entendimento de um cenário de contaminação envolvendo gasolina e etanol uma vez que gasolina com 20 por cento de etanol em sua constituição e etanol puro estão sendo utilizados como combustível, no Brasil, nos últimos 20 anos. O uso de aditivos oxigenados à gasolina, tais como álcoois, objetiva aumentar o desempenho do motor dos automóveis bem como diminuir a emissão de CO2 destes para a atmosfera e este uso vem aumentando em muitos países. Experimentos tipo equilíbrio em lote e experimentos de coluna foram realizados para investigar efeitos do etanol na solubilidade de constituintes da gasolina e no coeficiente de transferência de massa da gasolina para fase aquosa. Colunas de solo arenoso com gasolina em saturação residual foram percoladas por soluções aquosas com diferentes teores de etanol. Os resultados das concentrações efluentes de contaminante ao longo do tempo, obtidas destes ensaios, foram interpretados segundo o modelo de dissolução proposto por Frind et al. (1997), modificado nesta tese para considerar os efeitos de cosolvência do etanol na solubilidade dos constituintes da gasolina. Os resultados experimentais obtidos indicam que um cenário de contaminação envolvendo etanol e gasolina deverá ser bastante diferente daquele de contaminação usual de gasolina.Em um cenário de contaminação envolvendo etanol e gasolina, concentrações mais altas de contaminantes na água serão esperadas bem como diferentes constituintes da gasolina, além do tradicional grupo BTEX (benzeno, tolueno, etilbenzeno e os isômeros xilenos) deverão estar presentes na água em concentrações nocivas ao meio ambiente. / [en] Many organic contaminants, including petroleum products, such as gasoline, have low aqueous solubilities and migrate through the subsurface as a separated phase called NAPLs (non aqueous liquid phases). In its flow path into the porous media the NAPLs let behind disconnected segments of organic liquids entrapped as ganglia or lenses that form the residual phase of the contaminant. The presence of the residual contaminant has been reported as one of the most difficulties in the development of an appropriate cleanup strategy as the residual phase represents a long and continuum source of contamination of soils and groundwater, specially by its dissolution into the water.In this thesis the effect of ethanol on dissolution of residual gasoline was studied, aiming at a better understanding of a scenario of groundwater contamination involving gasoline and ethanol, since 20 percent of ethanol has been added to the Brazilian gasoline in the last 20 years and also ethanol has been used as fuel in Brazil in these years. The use of oxygenated additives into the gasoline, such as alcohols, has the advantage of improving engine performance and reducing the air impact pollution by CO2 and its use has increasing in many countries.Equilibrium batch tests and column experiments were carried out to investigate the effect of ethanol on solubility of gasoline constituents and on the mass transfer coefficient from gasoline to aqueous phase. The results of the column experiments were interpreted with a dissolution numerical model proposed by Frind et al.(1997), modified in this thesis to include the cosolvent effects of the ethanol on the solubility of gasoline constituents.In terms of soil and groundwater contamination related to gasoline spills, chemicals like benzene, toluene, ethylbenzene and xylenes (BTEX group) have acute toxicity or carcinogenicity, are the most water- soluble and mobile gasoline components, receiving the greatest concern. In this work, an enormous enhancement of gasoline constituents solubility due to ethanol was observed, and it was also noticed that the mass transfer coefficient diminished due to ethanol. The highest increase in solubility were for the less water soluble components. Therefore, gasoline components, other than BTEX, are expected in significant concentrations, in a scenario of contamination involving ethanol and therefore more concern about this potential threat should be addressed.

Den vanligaste biopolymeren på jorden är cellulosa och det är ett viktigt material i utvecklingen mot ett hållbart samhälle. Cellulosan och dess egenskaper kan modifieras genom kemiska reaktioner. Reaktiviteten hos cellulosans OH-grupper är låg på grund av en tät kristallstruktur, men kan förbättras genom t.ex. svällning eller upplösning följt av utfällning. I det här projeket kommer cellulosa från tre källor, microkristallin cellulose (Avicel), lövedsmassa (björk och asp) och barrvedsmassa (tall och gran) att lösas upp i natriumhydroxid och sedan fällas ut med två olika syror och ett organiskt lösningsmedel. Syrorna som användes var ättiksyra och svavelsyra och det organiska lösningsmedlet var etanol. Därefter jämfördes utbytet av den utfällda cellulosan.  Upplösning av Avicel 2.5 viktprocent gjordes i natriumhydroxid-lösning (10%) vid 5 oC och fälldes ut med de tre fällningsmedlen för att bestämma vilket som gav högst utbyte. Ättiksyra gav de bästa resultaten och användes i följande experiment på massa. Massornas löslighet var låg och den olösta massan var tvungen att separeras genom centrifugering innan utfällning av lösningen kunde göras. Hydrolys av massorna utfördes för att öka lösligheten och utfällningsutbytet. Upplösning av Avicel i kall natriumhydroxid och utfällning var framgångsrik. Utbytet vid utfällning med syror var högt. Det fanns ingen topp för maximalt utbyte när syrorna användes som antilösningsmedel, men etanol hade ett maximalt utbyte men lägre än för syrorna. Resultaten med massa var inte lika bra som för Avicel. De separerade olösta delarna var stora för båda massorna, men HW hade större del olöst material. Utbytet av fällning var lågt eftersom det fanns mindre cellulosa upplöst som kunde fällas ut. Hydrolysen av HW och SW var framgångsrik. Detta gjorde det möjligt att lösa upp och fälla ut mer cellulosa från massan. / Cellulose is the most abundant biopolymer on earth and is an important material in developing a sustainable society. The properties of cellulose can be modified by chemical treatment or reactions. The reactivity is fairly low in crystalline cellulose but can be increased if the dense crystal structure is disrupted by e.g. swelling or dissolution followed by precipitation. Dissolution of cellulose is difficult and this project aims to dissolve cellulose from three sources (Avicel and two sulfate pulps). One of the pulps had a tiny fraction of softwood and mostly birch and aspen, hardwood pulp (HW). The other of the pulps was made of pine and spruce, softwood pulp (SW). The raw materials were dissolved in sodium hydroxide (NaOH) and then precipitated with two acids and an anti-solvent (acetic acid (HOAc), sulfuric acid (H2SO4), or ethanol (EtOH)). The yields of the precipitated products were compared. Avicel 2.5 wt% was dissolved in NaOH solution (10%) at 5 oC and precipitated with the two acids and EtOH to determine the highest yield. HOAc gave the best results and was used in the following experiments on pulp. The solubility of pulps was low and the undissolved pulp had to be separated by centrifugation before precipitation of the solution. Hydrolyzation of the pulps was performed to increase the solubility and the precipitation yield. Dissolution of Avicel in cold NaOH and precipitation was successful. The yield at precipitation with acids was high. There was no peak of maximal yield when the acids were used to precipitate, but EtOH had a maximal yield but lower than for the acids. The results with pulp were not as good as for Avicel. The separated undissolved parts were big for both pulps, but HW was the worst. The yield of precipitation was low as there was less cellulose dissolved that could be precipitated. The hydrolysis of HW and SW was successful. This made it possible to dissolve and precipitate more cellulose from the pulp.

<p dir="ltr">Amorphous solid dispersions (ASDs) are being widely used as enabling formulations for poorly water soluble drugs. An ASD is a molecular level mixture of an amorphous drug and a polymer to form a single-phase homogeneous blend. The amorphous form of a drug provides a higher transient solubility compared to equilibrium crystalline solubility, whereby the presence of a polymer of appropriate properties aids in crystallization inhibition. Polymers also improve the release rate of the drug from the ASD relative to the release rate of neat amorphous drug, specifically for release regimens where both drug and polymer release congruently. Hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs tend to show congruent release of drug and polymer across multiple drug loadings, providing a significant dissolution improvement even beyond the amorphous solubility of a drug. Enteric polymers such as HPMCAS have been studied extensively in terms of enteric coated tablets but haven’t been explored in as much detail when molecularly dispersed with a drug as in case of ASDs. Literature shows not all ASDs are able to improve bioavailability of drugs. Such a failure to provide bioavailability advantage via certain ASDs could come from a randomized drug and polymer selection in the preformulation stage of drug product development which could fundamentally arise from the lack of understanding of the release mechanisms of ASDs. Given that HPMCAS is one of the most popularly used polymers for spray drying of ASDs in the pharmaceutical industry, investigating the release mechanisms of HPMCAS-based ASDs is critical. In this study, some of the key formulation design factors, such as drug-polymer interactions, different grades of polymer as well as dissolution media factors such as buffer capacity that impact the release performance of HPMCAS-based ASDs have been investigated. The results from this study are expected to contribute to the fundamental understanding of the failure mechanisms of HPMCAS-based ASDs, reducing empirical screening of drugs during the preformulation stage of the product development and enhance the success rate of ASDs.</p>

Yes / In vitro dissolution testing as a form of quality control has become a necessity in the pharmaceutical industry. As such, the need to establish a method that investigates the in vitro dissolution profile of inhaled products should be taken into account. The prime focus in this study was to examine the in-vitro in-vivo correlation utilising a modified version of the Twin Stage Impinger and to promote an in vitro dissolution model by enhancing the Fine Particle Dose (FPD) collection method for dry powder inhalers. The Twin Impinger was modified by inserting a stainless steel membrane holder disk in the base of the lower chamber. The design, with optimum drug deposition, was adopted for the dissolution study of budesonide and salbutamol. Afterwards, the membrane holder system was placed in the bottom of the dissolution vessel. Phosphate buffer saline (PBS), simulated lung fluid (SLF, Gamble solution) and Phosphate buffer (PB) were used in the study. The paddle dissolution apparatus, containing 300 mL of the medium, was operated at 75 rpm paddle speed. Samples were collected at defined time intervals and analysed using a validated HPLC method. The largest proportion of the budesonide dose was dissolved in PBS compared to PB and SLF. This was due to the presence of surfactant (0.2% w/v polysorbate), which enhances the wettability and the solubility of the poorly soluble drug (budesonide). The similarity factors for PBS and PB were 47.6 and 69.7, respectively, using SLF as a reference, whereas the similarity factor for salbutamol dissolution between PB and SLF was 81.3, suggesting PB is a suitable substitute. Comparison using both the predicted and actual in vivo pharmacokinetics (PK) values of the two drugs, as well as the pattern of their Concentration-Time (c-t) profiles, showed good similarity, which gave an indication of the validity of this in vitro dissolution method.

Yes / Despite the significant role that multiparty international joint ventures (MPIJVs) play within multinational enterprises, we know little about the significant challenges associated with the management of these ventures. Therefore, we combine the Resource-based View of the Firm and Transaction Cost Economics to investigate the effects of the key aspects of partner diversity (i.e., variety, balance, and disparity) on MPIJV dissolution. We test our hypotheses using a dataset of 248 MPIJVs in China. We find empirical support for a U-curve shaped effect of variety and a negative linear effect of balance on MPIJV dissolution.

No / The increasing prevalence of poorly soluble drugs in development provides notable risk of new products demonstrating low and erratic bioavailabilty with consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Although numerous strategies exist for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet able to be guaranteed and is greatly dependent on the physical and chemical nature of the molecules being developed. Crystal engineering offers a number of routes to improved solubility and dissolution rate, which can be adopted through an in-depth knowledge of crystallisation processes and the molecular properties of active pharmaceutical ingredients. This article covers the concept and theory of crystal engineering and discusses the potential benefits, disadvantages and methods of preparation of co-crystals, metastable polymorphs, high-energy amorphous forms and ultrafine particles. Also considered within this review is the influence of crystallisation conditions on crystal habit and particle morphology with potential implications for dissolution and oral absorption.

La dissolution acide est une technique efficace et communément utilisée pour dissoudre des échantillons environnementaux. En revanche, cette technique possède de nombreux problèmes, incluant sa vitesse d'exécution, l'utilisation d'acides potentiellement dangereux et sa digestion incomplète de composés réfractaires comme les oxydes d'actinides. Une méthodologie améliorée basée sur la dissolution par fusion automatisée suivie par de la chromatographie d'extraction pour la détection et la quantification des actinides dans des échantillons environnementaux a été développée. Un protocole de fusion pour la calcination complète et la dissolution de divers échantillons a été optimisé. La contamination croisée entre les échantillons a été étudiée et les résultats démontrent qu'un tel phénomène est négligeable, et ce, même sans le lavage des creusets entre les échantillons. L'unité de fusion automatisée améliore aussi la répétabilité dans la préparation des échantillons comparativement à des fusions dites manuelles. Les problèmes instrumentaux dus à la présence d'une haute concentration en lithium dans les solutions après la fusion au métaborate de lithium ont aussi été examinés. Conséquemment, une méthode utilisant la chromatographie d'extraction a été développée pour réduire la charge en métaborate de lithium et minimiser la matrice environnementale tout en conservant tous les actinides en solution. La méthode globale a été validée à l'aide de plusieurs échantillons de référence certifiés de nature différente. La possibilité d'appliquer cette technique à d'autres éléments a aussi été tentée. Cette méthodologie a aussi été appliquée à la détection d'uranium aéroporté dans trois villes québécoises : Kuujjuurapik, Montréal et Québec.