Thesis (Ph. D.)--University of Wisconsin--Madison, 1965. / Typescript. Errata list included after leaf 101. Vita. Description based on print version record. Includes bibliographical references (leaves 91-95).

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 96-99).

Thesis (Ph.D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 157 pages. Includes Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 78-82).

Glucocorticoids are used for many purposes in veterinary medicine but often come with significant adverse effects. Polyuria and polydipsia are the most common adverse effects noted by owners. To determine whether administration of desmopressin ameliorated the polyuria and polydipsia, a prospective study with 7 healthy Walker Hounds was performed. Daily water intake and urine specific gravity were measured in dogs under 4 separate conditions: no medications, prednisolone only, prednisolone and desmopressin, and prednisolone immediately after discontinuation of desmopressin. When compared to baseline, six out of seven dogs became polydipsic after administration of prednisolone twice daily. When desmopressin was administered to dogs receiving prednisolone, there was a statistically significant decrease in water intake and sodium concentration, and a significant increase in urine specific gravity. This suggests that desmopressin ameliorates the most significant side effect of prednisolone noted by owners, but that hyponatremia is an important complication associated with desmopressin.

Dissertation (Ph.D.)--Auburn University, 2005. / Abstract. Vita. Includes bibliographic references.

Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2006. / LICL has E-Thesis 0012 ; please contact computer services. LIRV has E-Thesis 0012 ; please contact circulation services.

no / This study employs artificial neural networks (ANNs) to create a model to identify relationships between variables affecting drug nanoprecipitation using microfluidic reactors. The input variables examined were saturation levels of prednisolone, solvent and antisolvent flowrates, microreactor inlet angles and internal diameters, while particle size was the single output. ANNs software was used to analyse a set of data obtained by random selection of the variables. The developed model was then assessed using a separate set of validation data and provided good agreement with the observed results. The antisolvent flow rate was found to have the dominant role on determining final particle size.

no / Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2 K are reported. The solubility of drugs was increased with the addition of ethanol and reached the maximum values of the volume fractions of 90 %, 80 %, and 80 % of ethanol. The Jouyban-Acree model was used to fit the experimental data, and the solubilities were reproduced using previously trained versions of the Jouyban-Acree model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the models were 5.1 %, 6.4 %, 37.7 %, and 35.9 %, respectively, for the fitted model, the trained version for ethanol + water mixtures, and generally trained versions for various organic solvents + water mixtures. Solubilities were also predicted by a previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.

Over recent years the delivery of nanosized drug particles has shown potential in improving bioavailability. Drug nanosizing is achieved by 'top-down' and by 'bottom-up' approaches. Owing to limitations associated with the top-down techniques, such as high energy input, electrostatic effects, broad particle size distributions and contamination issues, great interest has been directed to alternative bottom up technologies. In this study, the hypothesis that microreactors can be used as a simple and cost-effective technique to generate organic nanosized products is tested using three steroids (hydrocortisone, prednisolone and budesonide). Arrested antisolvent nanoprecipitation using ethanol (solvent) and water (antisolvent) was conducted within the microreactors. To enable experimental design for the microreactor studies, solubility profiles in different ethanol-water combinations at 25 °C were explored. All three drugs' solubility increased with increasing ethanol concentration showing maxima at 80-90 % v/v ethanol-water mixtures. Because of the complex multivariate microfluidic process, artificial neural network modelling was then employed to identify the dominant relationships between the variables affecting nanoprecipitation (as inputs) and the drug particle size (as output). The antisolvent flow rate was found to have the major role in directing drug particle size. Based on these successful findings, the potential of preparing pharmaceutical nanosuspensions using microfluidic reactors was researched. A hydrocortisone (HC) nanosuspension (NS) was prepared by introducing the generated drug particles into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared NS. Results showed that a stable narrow sized HC NS of amorphous spherical particles 500 ± 64 nm diameter and zeta potential -18 ± 2.84 mV could be produced. The ocular bioavailability of a microfluidic precipitated HC NS (300 nm) was assessed and compared to a similar sized, milled HC NS and HC solution as a control. The precipitated and the milled NS achieved comparable AUC0-9h of 28.06 ± 4.08 and 30.95 ± 2.2, respectively, significantly (P < 0.01) higher than HC solution (15.86 ± 2.7). These results illustrate the opportunity to design sustained release ophthalmic formulations. Going nano via microfluidic precipitation was also exploited to tailor budesonide (BD) NS for pulmonary administration. The in vitro aerosolization by nebulization of a BD NS was studied in comparison with a commercial BD microsuspension. Overall, the fine particle fraction generated from BD NS (56.88 ± 3.37) was significantly (P < 0.05) higher than the marketed BD (38.04 ± 7.81). The mean mass aerodynamic diameter of BD NS aerosol (3.9 ± 0.48 μm) was significantly smaller (P < 0.05) than the microsuspension (6.2 ± 1.09 μm) indicating improved performance for BD NS. In conclusion, findings of this study support the hypothesis of using microfluidic nanoprecipitation as a promising and economical technique of drug nanosizing.