Browsing by Subject "Dissolution"
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Item Advanced formulation and processing technologies in the oral delivery of poorly water-soluble drugs(2013-08) Lang, Bo, 1986-; Williams, Robert O., 1956-With the advance of combinational chemistry and high throughput screening, an increasing number of pharmacologically active compounds have been discovered and developed. A significant proportion of those drug candidates are poorly water-soluble, thereby exhibiting limited absorption profiles after oral administration. Therefore, advanced formulation and processing technologies are demanded in order to overcome the biopharmaceutical limits of poorly water-soluble drugs. A number of pharmaceutical technologies have been investigated to address the solubility issue, such as particle size reduction, salt formation, lipid-based formulation, and solubilization. Within the scope of this dissertation, two of the pharmaceutical technologies were investigated names thin film freezing and hot-melt extrusion. The overall goal of the research was to improve the oral bioavailability of poorly water-soluble drugs by producing amorphous solid dispersion systems with enhanced wetting, dissolution, and supersaturation properties. In Chapter 1, the pharmaceutical applications of hot-melt extrusion technology was reviewed. The formulation and process development of hot-melt extrusion was discussed. In Chapter 2, we investigated the use of thin film freezing technology combined with template emulsion system to improve the dissolution and wetting properties of itraconazole (ITZ). The effects of formulation variables (i.e., the selection of polymeric excipients and surfactants) and process variables (i.e., template emulsion system versus cosolvent system) were studied. The physic-chemical properties and dissolution properties of thin film freezing compositions were characterized extensively. In Chapter 3 and Chapter 4, we investigated hot-melt extrusion technology for producing amorphous solid dispersion systems and improving the dissolution and absorption of ITZ. Formulation variables (i.e., the selection of hydrophilic additives, the selection of polymeric carriers) and process variables (i.e., the screw configuration of hot-melt extrusion systems) were investigated in order to optimize the performance of ITZ amorphous solid dispersions. The effects of formulation and process variables on the properties of hot-melt extrusion compositions were investigated. In vivo studies revealed that the oral administration of advanced ITZ amorphous solid dispersion formulations rendered enhanced oral bioavailability of the drug in the rat model. Results indicated that novel formulation and processing technologies are viable approaches for enhancing the oral absorption of poorly water-soluble drugs.Item An analysis of salt welding(2010-05) Wagner, Bryce Hedrick; Jackson, M. P. A.; Cloos, Mark; Hudec, Mike; Steel, Ron; Sen, Mrinal; Peel, FrankSalt can be removed by viscous flow and dissolution to form a salt weld. A complete weld forms when salt is completely removed by these processes. Where salt removal is incomplete, a partial weld forms. Though welds are frequently mentioned in the literature, the details of weld formation and the properties of salt welds are poorly understood. In Chapter 1, I use analytical and numerical models to quantify the role of viscous flow during salt welding. Where salt flow is limited by boundary drag against the salt contacts, evacuation is slow and up to ~50 m of salt will be left behind in a partial weld. Where salt flow is laterally unrestricted, a vanishingly thin (<< 1 m) smear of salt will remain. I conclude that layer-parallel wall rock translation or dissolution must act to remove any remnant salt to create a complete weld. In Chapter 2, I characterize partial welds containing halite and anhydrite on reflection seismic data by treating welds as thin beds. Below the temporal resolution of reflection seismic data, typically ~25-50 m for modern surveys with peak frequencies of ~10-30 Hz, reflections from the upper and lower evaporite contacts converge and interfere to form a single composite reflection. Thus, partial and complete welds are typically indistinguishable using travel-time differences alone. I then use amplitude information from synthetics and seismic examples to estimate remnant evaporite thickness. In Chapter 3, I investigate fluid flow near and through salt welds. I conclude dissolution during boundary flow can remove up to a few meters of salt per million years. Though dissolution plays a volumetrically insignificant but important role in weld formation, as runaway dissolution can create pathways for focused cross-weld migration of subsurface fluids. I identify features that influence cross-weld migration of subsurface fluids and then develop an empirical relationship between weld geometry and the tendency seal or leak hydrocarbons. I find that in the Campos Basin, offshore Brazil, salt welds containing remnant evaporites thinner than ~50 m that are broader than ~25 km2 in area are likely to leak.Item Determination of petroleum pipe scale solubility in simulated lung fluid(Texas A&M University, 2005-08-29) Cezeaux, Jason RoderickNaturally occurring radioactive material (NORM) exists in connate waters and, under the right conditions during oil drilling, can plate out on the interior surfaces of oil and gas industry equipment. Once deposited, this material is commonly referred to as ??scale.?? This thesis is concerned with the presence of 226Ra in scale deposited on the inner surfaces of oil drilling pipes and the internal dose consequences of inhalation of that scale once released. In the process of normal operation, barium sulfate scale with a radium component adheres to the inside of downhole tubulars in oil fields. When crude flow is diminished below acceptable operational requirements, the pipe is sent to a descaling operation to be cleaned, most likely by a method known as rattling. The rattling process generates dust. This research investigated the chemical composition of that aerosol and measured the solubility of pipe scale from three oilfield formations. Using standard in-vitro dissolution experimental equipment and methods, pipe scale is introduced into simulated lung fluid over a two-week period. These samples are analyzed using quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), known for very low detection limits. Analysis reveals virtually no 226Ra present in the lung fluid exposed to pipe scale. Sample measurements were compared against background measurements using Student??s t test, which revealed that nearly all the samples were statistically insignificant in comparison to the lung fluid blanks. This statistical test proves within a 95% confidence interval that there is no 226Ra present in the lung fluid samples. These results indicate that inhaled NORM pipe scale should be classified as Class S and serve to further confirm the extreme insolubility of petroleum pipe scale. For dose calculations, the S classification means that the lung is the main organ of concern. Radium-226 from petroleum pipe scale does not solubilize in the interstitial lung fluid, and does not, therefore, enter the bloodstream via respiratory pathways. Since there is no removal by dissolution, the 500 day biological half-life implied by the S classification is based solely on the mechanical transport of 226Ra out of the lungs by phagocytosis or the mucociliary escalator.Item Dissolution of oxygen reduction electrocatalysts in acidic environment(2009-05-15) Gu, ZhihuiPlatinum (Pt) alloy nanoparticles are used as catalysts in electrochemical cells to reduce oxygen to water and to oxidize hydrogen; the overall reaction converts chemical energy into electrical energy. These nanocatalysts are deposited on a carbon substrate and their catalytic function takes place in acid medium. This harsh environment causes an undesired reaction, which is the dissolution of the metal atoms into the acid medium; thus affecting the catalyst life. This dissertation aims to investigate the dissolution mechanism of fuel cell cathode catalysts at the atomic level starting from the oxygen reaction intermediates on the cathode catalyst surface and propose guidelines to improve cathode catalysts durability based on our proposed mechanism. Density functional theory is employed to study various possible scenarios with the goals of understanding the mechanism of the metal atom dissolution process and establishing some guidelines that permit a rational design of catalysts with better stability against dissolution. A thermodynamic analysis of potential metal dissolution reactions in acid medium is presented first, using density functional theory calculations to explore the relative stabilities of transition metals in relation to that of Pt. The study is performed by comparing the change in reaction Gibbs free energies for different metals in a given dissolution reaction. Then, a series of density functional theory studies, tending to investigate the adsorbed atomic oxygen absorption process from cathode catalyst surface into its subsurface, includes: 1) the oxygen adsorption on various catalyst surfaces and oxygen absorption in subsurface sites to figure out the minimum energy pathway and energy barrier of on-surface oxygen migration and absorption into subsurface; 2) the oxygen coverage, the other oxygen reduction reaction intermediates, and water effects on the oxygen absorption process according to reaction pathways, energy barriers, and thermodynamic analysis; 3) the oxygen absorption process on several Pt-based alloys with various compositions and components to find out the best alloy to inhibit atomic oxygen absorption including both kinetic and thermodynamic analyses, and the effects of such alloyed species on the inhibition process.Item Dry powder antibiotics for inhaled anti-tuberculosis therapy(2010-12) Son, Yoen Ju; McConville, Jason Thomas; McGinity, James W.; Williams, Robert O.; Wiederhold, Nathan; Roy, KrishnenduThe aim of this research was to develop and fully investigate a novel method of antibiotic drug delivery to the lung that will address problems with current therapeutic regimens for treatment of airway infections. To demonstrate the performance of prepared formulations, the design of suitable characterization methods were also aimed. A novel dissolution method for evaluating the in vitro dissolution behavior of inhalation formulations was developed. The membrane holder was designed to enclose previously air-classified formulations so that they could be uniformly tested in the dissolution apparatus. Dissolution procedures, the apparatus, the dose collection, the medium, and test conditions were developed and the dissolution behaviors of test compounds were evaluated by experimental and mathematical analysis. It was proved that the aerodynamic separation of formulation prior to dissolution assessment have a significant influence on the dissolution profiles. The optimized test method using the membrane holder was applied to evaluate in vitro dissolution profiles of the manufactured formulations of rifampicin (RF). The carrier/excipient-free RF dry powder formulation was investigated. The rifampicin dihydrate (RFDH) powders having MMAD of 2.2 um were prepared using a simple recrystallization process. The RFDH powders have a thin flaky structure, and this unique morphology provides improved aerosolization properties at maximal API loading. The manufactured RFDH formulation showed 80% drug release within 2 hours. To retard the release rate of RF, the prepared RFDH crystals were coated with hydrophobic polymer, PLA or PLGA, using spray-dryer equipped with multi-channel spray nozzles. The multi-channel spray nozzle used in this study has two separate nozzles for aqueous solution and one for gas fluid. The RFDH crystals and the coating solutions were sprayed through the two separate liquid nozzles at the same time. The coated RFDH formulations were prepared using multi-channel spray nozzles. The coated formulations contained at least 50% w/w of RF with no change of their flaky morphology. The initial RF release was lowered by coating; the lowest initial RF release was observed from the coated powders with PLA polymer as 32% among the coated formulations. Overall, the 80% of RF was released within 8 hours. The RFDH and coated RFDH formulations delivered via the pulmonary route would be anticipated to provide higher local (lung) drug concentrations than that of orally delivered powders. Particularly, the coated RFDH powders deposited in the alveolar region may prolong the drug residence time in the site of infections. Additionally, it was proved that the RFDH and coated RFDH formulations provided much better stability than the amorphous RF.Item Examining supercritical CO₂ dissolution kinetics during carbon sequestration through column experiments(2011-08) Kent, Molly Elizabeth; Bennett, Philip C. (Philip Charles), 1959-; Romanak, Katherine; Cardenas, Meinhard B.Carbon sequestration is a method of capturing and storing excess anthropogenic CO₂ in the subsurface. When CO₂ is injected, the temperature and pressure at depth turn it into a supercritical (SC) fluid, where density is that of a liquid, but viscosity and compressibility resemble a gas. Ultimately the SC CO₂ is trapped at depth either by low permeability sealing layers, by reactions with minerals, or by dissolving into fluids. The injected CO₂ is buoyant and initially exists as a non-aqueous hydrophobic layer floating on top of the subsurface brine, up against the upper sealing formation, but over time it will dissolve into the brine and potentially react with minerals. The details of that initial dissolution reaction, however, are only poorly understood, and I address three basic questions for this research: What is the fundamental kinetics of SC CO₂ dissolution into water? How fast does dissolved CO₂ diffuse away from the source point? And what geochemical conditions influence the dissolution rate? To answer these questions I employed a high pressure flow-through approach using a column packed with coarse quartz sand. The system was both pressure and temperature controlled to have either liquid or SC CO₂ present, and was typically run at 100 Bar, 0.5 to 2.5 mls/min, and 28-60°C. After establishing the hydraulic parameters for the column using two conservative tracers (Br, As), injections (5 and 20 [mu]l) were made either as aqueous solutions equilibrated to high pressure CO₂, or as pure liquid or SC CO₂ into 0.1 mmol NaOH. For all experiments the pH of the system was monitored, and [CO₂] over time was calculated from those data. For injections of brine with dissolved CO₂, transport was conservative and was nearly identical to the conservative tracers. The CO₂ quickly mixes in the column and does not react with the quartz. The liquid and SC CO₂ injections, however, do not act conservatively, and have a very long tailing breakthrough curve that extends to tens of pore volumes. I hypothesize that the SC CO₂ is becoming trapped as a droplet or many droplets in the pore spaces, and the long breakthrough tail is related either to the rate of dissolution into the aqueous phase, the diffusion of dissolved CO₂ away from the phase boundary, or the reaction with the NaOH, limited to the narrow contact zones in the pore throats. Because of the speed at which acid-base reactions occur (nanosecond kinetics), I infer that the rate limiting step is either surface dissolution or diffusion. From plots of ln[CO₂] v. time I obtained values for k, the specific rate of the dissolution reaction R=-k[CO₂]. No trend for k was seen with respect to changes in temperature, but k did show a trend with respect to changing flow rate. k increased from an average value of 3.05x10⁻³ at 0.5 ml/min to an average value of 3.38x10⁻³ at 1.6 ml/min, and then held constant at the higher flow rates, up to 2.5 ml/min. I interpret these data to show that at low flow rates, the reaction is diffusion limited; the fluid nearest the contact zone becomes saturated with dissolved CO₂. At higher flow rates, the fluid is moving fast enough that saturation cannot occur, and the kinetics of the dissolution reaction dominate. Simple geometric models indicate that the CO₂/water interface is shaped like a spherical cap, indicating that the snapped-off CO₂ is forming a meniscus in the pore throat, limiting the surface area across which dissolution can occur.Item The temporal course of love : the developmental trajectories of passionate and companionate love and their connections to relationship dissolution(2013-12) Schoenfeld, Elizabeth Austin; Loving, Timothy J.; Huston, Ted L.It has long been believed that passionate love wanes over time, whereas companionate love grows stronger with time. Using a sample of individuals in dating relationships who reported on their feelings of love for their partners up to 20 times over the course of several months, I tested whether passionate love and companionate love develop across the early months of romantic involvement in a manner consistent with theory. Additionally, I investigated whether certain developmental trajectories of both varieties of love are more predictive of relationship dissolution than others. To do this, I first examined the average trajectories of passionate and companionate love for those who stayed together with their partners and those who experienced a breakup, paying special attention to extraneous factors that were expected to influence the manner in which both varieties of love changed over time. The amount of time individuals knew their partners prior to becoming romantically involved, their feelings of the opposing variety of love, the extent to which individuals wanted to break up with their partners, their perceptions of their partners’ desire to break up, and gender all informed the ways in which love changed over time. Because it was expected that passionate love and companionate love would show substantial heterogeneity in their temporal trajectories, I then identified the prototypical patterns of development for passionate and companionate love. The results for passionate love revealed eight distinct linear trajectories, and six unique linear trajectories were identified for companionate love. For passionate love, individuals who experienced stable or declining levels of love were more likely to experience a breakup, but the connection between companionate love and relationship dissolution was less straightforward. Perhaps most importantly, passionate and companionate love interacted to predict the likelihood of dissolution, such that, to the extent that individuals who reported higher levels of passionate love also reported stronger feelings of companionate love, the lower their odds of dissolution. The current findings both complement and extend prior theoretical and empirical work on the developmental trajectories of passionate and companionate love and their connections to relationship dissolution.