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Advisory Committee Chair

Timothy M Wick

Advisory Committee Members

Joel Berry

S Louis Bridges Jr

Joanne E Murphy-Ullrich

Andrew D Penman

Document Type

Dissertation

Date of Award

2016

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Delivering drugs through the skin reduces side effects and avoids first pass drug metabolism. This is especially advantageous for drugs with associated side effects due to oral administration such as the case of diclofenac sodium; a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of symptomatic pain of joints due to osteoarthritis. However, transdermal delivery of diclofenac relies on the use of topical formulations that require constant application and are inconvenient for daily activities. These factors reduce patient compliance and diminish the efficacy of transdermal delivery of diclofenac. Improving transdermal delivery of diclofenac in joints or extremities requires developing novel formulations that can be incorporated into transdermal systems designed for these areas. The formulations should improve drug permeation and provide controlled release over longer periods of time. In this work a semisolid gel and a solid hydrogel film formulation were developed with the goal of improving transdermal drug permeation and controlled release. The effects of varying levels of chemical penetration enhancers and the gelling agent gellan gum on the permeation of diclofenac were evaluated. To accelerate formulation development, drug permeation studies were performed using a modified transwell diffusion system with a synthetic skin membrane or human epidermis. Optimized versions of the semisolid gel and solid hydrogel film formulations showed increased diclofenac transport as compared to currently available topical diclofenac formulations. In addition, to provide additional control of drug release from the formulations, the use of temperature sensitive diclofenac containing nanogels was explored. The addition of temperature sensitive nanogels into the solid hydrogel film increases diclofenac transport at skin temperature of 32 °C compared to solid hydrogel films at 22 °C. As an approach to control the release of diclofenac from a transdermal drug delivery device that uses the formulations developed, the semisolid gel and solid hydrogel film formulations were applied in combination and device design parameters such as transport area and drug concentration in each formulation were varied to control the release of diclofenac. These studies are significant because the formulations developed improved transdermal transport of diclofenac in synthetic membranes and human epidermis compared to commercial diclofenac transdermal formulations.

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