Thesis (Ph. D.)--University of North Texas, Aug., 2009. / Title from title page display. Includes bibliographical references.

Thesis (M.S.)--Naval Postgraduate School, 2002. / Thesis advisor(s):David R. Henderson, Douglas Moses. Includes bibliographical references (p. 123-132). Also available online.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.

Thesis (M.S.W.)--University of Hong Kong, 1987.

Low water solubility of drug compounds limits their dissolution in the aqueous body fluids. When formulated using conventional methods, those poorly water-soluble drugs often results in low and erratic bioavailability. The use of nanoparticle engineering technologies for the formulation of poorly water-soluble drugs is a valuable strategy to enhance dissolution rates and thus bioavailability. In Chapter 2, a nanoparticle engineering process, Evaporative Precipitation into Aqueous Solution (EPAS), was modified to provide improved control over the size of precipitated particles. The improved process, Advanced EPAS, was employed to prepare nanoparticles of the poorly water-soluble drug itraconazole (ITZ). The influence of processing parameters and formulation aspects on the size of suspended ITZ-particles was investigated. The process was shown to be robust such that the size distribution of dispersed nanoparticles was largely independent across the different parameters. In Chapter 3, aqueous nanoparticulate dispersions of the poorly soluble drug mefenamic acid (MFA) were developed and subsequently incorporated into controlled release formulations employing spray-drying. Release of MFA from spray-dried formulations was sustained and complete demonstrating the feasibility of using nanoparticulates for the preparation of controlled release systems. In Chapter 4, the nanoparticle engineering process, Rapid Freezing (RF), was utilized to produce nanostructured, amorphous aggregates of the poorly water soluble drug ketoprofen (RF-KET). The stability of RF-KET against recrystallization was improved through the deposition of a hydrophobic plasma-polymerized film. The coating presented an effective barrier against surface mobility and moisture uptake resulting in enhanced stability of RF-KET for up to six months at accelerated storage conditions as compared to three days for uncoated RF-KET. / text

published_or_final_version / Medicine / Master / Master of Medical Sciences

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Dry powder coating of pharmaceutical dosage forms has been investigated as an alternative method to commonly used liquid based coating techniques. Eudragit[trademark] L 100-55 and Eudragit[trademark] L 30 D-55 have been employed in enteric film coatings using aqueous dispersions, organic solutions and compression coating. However, the copolymer has not been investigated in dry powder coating applications. Initially, formulation factors and processing parameters were investigated for the dry powder coating of chlorpheniramine maleate tablets using Eudragit[trademark] L 100-55 as the delayed release polymer. Powder coating was studied as a method to prevent the migration of an ionizable, highly water soluble model drug into the polymeric film during the coating process. Eudragit[trademark] L 100-55 was pre-plasticized with triethyl citrate (TEC) using hot-melt extrusion and subsequently ground into a fine powder. Polyethylene glycol 3350 (PEG 3350) was used as a primer and low melting coating excipient to enhance coating powder adhesion and to improve film formation. The powder coating process was performed in a modified laboratory scale spheronizer. For the dry-powder coating of sodium valproate tablets different subcoating materials were investigated to improve powder adhesion to the substrate and to reduce the level of Eudragit[trademark] L 100-55 required for gastric resistance. PEG 3350 and Methocel[trademark] K4M were incorporated in the Eudragit[trademark] E PO and Eudragit[trademark] RL PO subcoating formulations as pore forming materials. The miscibility of the PEG 3350 and Methocel[trademark] K4M in the film coating was correlated with their ability to function as pore forming agent. The film formation process of thermally cured Eudragit[trademark] L 100-55 dry-powder coatings was characterized. The influence of film additives on relative melt viscosity, surface free energy of the polymer and the mechanical properties of powder-cast films was studied. The influence of Eudragit[trademark] E PO in Eudragit[trademark] L 100-55 film coatings applied by a dry powder coating technique on the drug release mechanism was investigated. Calculation of the Flory-Huggins interaction parameter based on solubility parameters and different analytical techniques demonstrated immiscibility of the copolymers at processing conditions. A broad range of pH dependent theophylline release profiles were obtained as a function of the polymer blend ratio. / text

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