Date of Award

Summer 2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Laurent Simon

Second Advisor

Piero M. Armenante

Third Advisor

Norman W. Loney

Fourth Advisor

Kun S. Hyun

Fifth Advisor

Bozena B. Michniak

Abstract

Three representative drug delivery systems were analyzed to emphasize the roles of mathematical models and computer-aided simulations in pharmaceutical research. In the first project, a protocol was developed so that the optimal regimen, consisting of the intravenous boluses and subsequent infusion of theophylline, could be obtained once information on the pharmacokinetics became available. The method was based on a two-compartment model of the human body. A module was created and posted on a website for free access. The second project dealt with the transdermal heat-assisted delivery of corticosterone. Heat conduction and drug diffusion through the patch and the skin were expressed in the mathematical model. Four design parameters were estimated. This model was validated using clinical data from the administration of fentanyl. Cortisone concentrations through the patch and skin layers were predicted. The results were used to rank the relative impacts of the design parameters on the corticosterone delivery and to make proper suggestions for fabricating the products. Finally, the simultaneous application of an electric current and soluble microneedles were proposed for the first time. Preliminary experimental studies suggested that the electric field enhanced the flux by increasing drug diffusion and, thereby, the dissolution of the microneedles. One-, two- and three-dimensional simulations were conducted. In addition, protocols were proposed to help with the analysis of laboratory data.

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