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1) Development and in vivo testing of a gastric retention device (GRD) in dogs : 2) product formulations and in vitro-in vivo evaluation of a) immediate release formulation of itraconazole, b) controlled-release formulation of ketoprofen in adultsKapsi, Shivakumar G. 24 November 1998 (has links)
This thesis describes 1) development of a gastric retention device (GRD) to
increase gastric retention time of certain drugs, 2) product formulations of an immediate
release itraconazole and controlled-release ketoprofen. GRD was fabricated from crosslinked
carbohydrate polymers. Rate and extent of hydration of the film in water and in
simulated gastric fluid, compressibility of film, shape of the film, and in vivo gastric
transit time in the stomach of dog were used as tools to evaluate gastric retention
properties. Hydration studies were carried out at 37��C. Evaluation of the device
containing radio-opaque agents, in dogs for gastric retention was carried out with the help
of X-rays. The device was found to stay in the stomach of dogs for at least 10 hours.
GRD containing amoxicillin trihydrate caplets were evaluated in a human. The area
under the excretion rate curve was found to increase by 30% when compared to without
the device.
A successful development of a formulation of water insoluble itraconazole,
without the use of organic solvents, was achieved with modifications from eutectic
mixture techniques. Solubilization of the drug was achieved in polyethylene glycol of
higher molecular weight. A series of formulations made by varying the amounts
ingredients therein, were evaluated for dissolution profile in comparison with the
reference, Sporanox��. Effect of molecular weights of PEG and types of PEG were
evaluated for desired drug dissolution. Preliminary study from 6 subjects under the
conditions of fasting and fed indicated that bioavailability from the new formulation was
increased slightly when compared to the reference. This may be correlated to difference
in the rate of in vitro dissolution, where the new formulation has initial faster dissolution.
A controlled-release formulation of ketoprofen was also developed using a
diffusion-controlled polymer, which was coated onto the drug beads. Release of drugs
from such beads is controlled by the thickness of the coat. Thickness of the coat was
evaluated by SEM and was correlated to the desired in vitro drug release in comparison
to the reference Oruvail��. A three-way cross over study involving the new formulation
and two marketed products in 12 subjects under fasting conditions indicated that there
was a significant difference between the new product and marketed products, so as to be
considered non-bioequivalent. Use of In Vitro-In Vivo Correlations and Convolution-
Deconvolution relations predicted desired in vitro drug dissolution in a subsequent
modification of the formulation. / Graduation date: 1999
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Evaluation of potential multi-particulate drug delivery systems /Murty, Aruna Mummini. January 2006 (has links)
Thesis (Ph. D.)--University of Rhode Island, 2006. / Typescript. Includes bibliographical references (leaves 210-235).
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Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles : Applications in Life SciencesKupferschmidt, Natalia January 2013 (has links)
Mesoporous silica particles offer great potential benefits as vehicles for drug delivery and in other biomedical applications. They present a high loading capacity due their ordered and size-tuneable pores that allow molecules to be loaded and released. In addition, they offer the possibility to enhance oral bioavailability of drugs with limited aqueous solubility and to protect pH sensitive drugs from the acidic conditions in the stomach on their way to the intestine. The aim of this thesis was to evaluate the biocompatibility and effects of mesoporous silica particles on immunocompetent cells. Subsequently, two potential life sciences applications were investigated: as adjuvants and as weight reduction agents. Adjuvants are used in vaccines in order to enhance the immunological response towards attenuated and poorly immunogenic antigens. Their function can be mediated through dendritic cells which have a central role in the control of adaptive immunity including immunological memory. Our results show that different types of mesoporous silica particles were able to tune the development of T cells both in human cell cultures and in mice. In contrast to the approved adjuvant alum (aluminium salts) which is a specific inducer of Th2-type immune responses, the particles induced more Th1-like responses, which may be desired in vaccines against allergy and intracellular pathogens such as viruses. Particle exposure to macrophages did not affect their cell function which is crucial for tissue homeostasis, wound repair and in prevention of autoimmune responses. Likewise, the cytokine secretion was not affected, which suggest that macrophages would not modulate the immune response towards the particles. Furthermore, mesoporous silica particles were highly tolerated at daily oral administrations of up to 2000 mg/kg doses for some of the materials prepared. Large pore mesoporous silica particles were shown to act as weight and body fat reduction agents without other observable pathological signs when administered in the diet of obese mice. Together; those results are promising for the development of mesoporous silica as drug delivery systems and adjuvants for oral administration of drugs or vaccines. Additionally, large pore mesoporous silica materials are potential agents for the treatment of obesity.
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Microgel Based Materials for Controlled Macromolecule DeliveryNolan, Christine Marie 10 April 2005 (has links)
This dissertation focuses on utilization of poly(N-isopropylacylamide) (pNIPAm) based mirogels for regulated macromolecule drug delivery applications. There is particular emphasis on incorporation of stimuli responsive materials into multi-layer thin film constructs with the main goal being fabrication of highly functional materials with tunable release characteristics. Chapter 1 gives a broad overview of hydrogel and microgel materials focusing on fundamental properties of pNIPAm derived materials. Chapter 2 illustrates the progression of controlled macromolecule release from hydrogel and microgel materials and sets up the scope of this thesis work. Chapter 3 details studies on thermally modulated insulin release from microgel thin films where extended pulsatile release capabilities are shown. Chapters 4 and 5 focus on more fundamental synthesis and characterization studies of PEG and acrylic acid modified pNIPAm microgels that could ultimately lead to the design of protein loaded microgel films with tunable release characteristics. Chapter 6 illustrates fundamental macromolecule loading strategies, which could also prove useful in future protein drug delivery design using stimuli responsive networks. Chapter 7 concentrates on direct insulin release studies that probe the interaction between entrapped and freely diffusing protein and microgels. These model experiments could prove useful in design of tunable macromolecule drug release from functionally modified microgels and could aid in the tailored design of peptide-loaded microgel thin films. Chapter 8 discusses the future outlook of controlled macromolecule release from microgel based materials.
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The design and synthesis of endosomal disruptive polymers /Murthy, Niren. January 2001 (has links)
Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 98-107).
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Physical-mechanical and chemical properties of topical films produced by hot-melt extrusion /Repka, Michael Andrew, January 2000 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 286-299). Available also in a digital version from Dissertation Abstracts.
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Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery /Kwok, Connie Sau-Kuen. January 2001 (has links)
Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 260-285).
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Polymeric microneedles for transdermal drug deliveryPark, Jung-Hwan, January 2004 (has links) (PDF)
Thesis (Ph. D.)--School of Biomedical Engineering, Georgia Institute of Technology, 2004. Directed by Mark R. Prausnitz. / Includes bibliographical references (leaves 184-193).
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Magnetic drug targeting Development of a novel drug delivery system for prostate cancer therapy/Rahimi, Maham. January 2008 (has links)
Thesis (Ph.D.) -- University of Texas at Arlington, 2008.
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Physicochemical and mechanical characterization of hot-melt extruded dosage formsCrowley, Michael McDonald 28 August 2008 (has links)
Not available / text
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