Browsing by Subject "Particle size"
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Item Development of an inhalational formulation of Coenzyme Q₁₀ to treat lung malignancies(2011-12) Carvalho, Thiago Cardoso; McConville, Jason ThomasCancer is the second leading cause of death in the United States and its onset is highly incident in the lungs, with very low long-term survival rates. Chemotherapy plays a significant role for lung cancer treatment, and pulmonary delivery may be a potential route for anticancer drug delivery to treat lung tumors. Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. In this work, we hypothesize that formulations of CoQ10 may be developed for pulmonary delivery with a satisfactory pharmacokinetic profile that will have the potential to improve a pharmacodynamic response when treating lung malignancies. The formulation design was to use a vibrating-mesh nebulizer to aerosolize aqueous dispersions of CoQ₁₀ stabilized by phospholipids physiologically found in the lungs. In the first study, a method was developed to measure the surface tension of liquids, a physicochemical property that has been shown to influence the aerosol output characteristics from vibrating-mesh nebulizers. Subsequently, this method was used, together with analysis of particle size distribution, zeta potential, and rheology, to further evaluate the factors influencing the capability of this nebulizer system to continuously and steadily aerosolize formulations of CoQ₁₀ prepared with high pressure homogenization. The aerosolization profile (nebulization performance and in vitro drug deposition of nebulized droplets) of formulations prepared with soybean lecithin, dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) were evaluated. The rheological behavior of these dispersions was found to be the factor that may be indicative of the aerosolization output profile. Finally, the pulmonary deposition and systemic distribution of CoQ₁₀ prepared as DMPC, DPPC, and DSPC dispersions were investigated in vivo in mice. It was found that high drug amounts were deposited and retained in the mouse lungs for at least 48 hours post nebulization. Systemic distribution was not observed and deposition in the nasal cavity occurred at a lower scale than in the lungs. This body of work provides evidence that CoQ₁₀ may be successfully formulated as dispersions to be aerosolized using vibrating-mesh nebulizers and achieve high drug deposition in the lungs during inhalation.Item Permeability estimation of damaged formations near wellbore(2011-05) Shi, Xiaoyan, 1977-; Gray, Kenneth E., Ph. D.; Prodanović, MašaFormation damage is a common problem in petroleum reservoirs and happens in different stages of reservoir development from drilling to production. The causes of formation damage include particle invasion, formation fines migration, chemical precipitation, and pore deformation or collapse. Formation damage adversely affects productivity of wells by reducing the permeability of near wellbore region. Furthermore, formation damage also affects well logging results. Therefore, understanding the mechanism of formation damage is vital to predict the extent and severity of formation damage and to control it. This thesis is focused on the study of formation damage caused by external particle invasion. A simplified numerical method based on a commercial code PFC (Particle Flow Code) is proposed to simulate the particle invasion process. The fluid-particle interaction is simplified as hydrodynamic drag forces acted on particles by fluids; the particle-grain interaction is modeled as two rigid balls on contact. Furthermore, an pore network flow model is developed in this study to estimate permeability of damaged formations, which contain two well-separated particle sizes. The effects of the particle size and the initial formation porosity on formation damage are studied in detail. Our study shows that big particles tend to occupy the formation face, while small particles invade deep into the formation. Moreover, particles which are smaller than pore throats (entrances) impair permeability more than those bigger than pore throats. Our study also indicates that a higher initial formation porosity results in more particle invasion and permeability impairment. It is suggested that, in order to reduce formation damage, mud particle size distributions should be carefully selected according to given formation properties. Although our model has some limitations, it may serve as a tool to predict formation damage according to given parameters, and to understand the mechanism of formation damage from a micro-scopic point of view.