Date of Award

1-31-2005

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Materials Science and Engineering - (Ph.D.)

Department

Committee for the Interdisciplinary Program in Materials Science and Engineering

First Advisor

Sirkar, Kamalesh K.

Second Advisor

Michniak, Bozena B.

Third Advisor

Wu, Jing

Fourth Advisor

Chin, Ken K.

Fifth Advisor

Kristol, David S.

Abstract

Novel approaches for transdermal drug delivery (TDD) based on a porous membrane-based aqueous-organic partitioning system have been investigated and successful deliveries were observed. Doxycycline hydrochloride (HCl), a polar antibiotic drug with a relatively large molecule weight (MW: 480.1) was studied as a basic model agent. Its controlled release using this technique was studied first. Satisfactory release profiles demonstrate the practical potential of such a system to achieve useful controlled release rates. The enhancer linoleic acid was essential to successful release using a mouse skin beneath a porous polymeric membrane. The transport rates of smaller molecules e.g., caffeine and nicotine from the same system without any enhancer were very high. Iontophoretic TDD was studied next using a porous polymeric conducting membrane of polyaniline (PANi). Doxycycline HCl, lidocaine HCl (MW: 271) and caffeine (MW:194) in their aqueous solutions were model agents. Excellent release profiles were achieved; the conducting PANi membrane appeared to be capable of not only replacing the Ag part of Ag|AgCl electrode system but also providing an additional control over agent transport rate. Aqueous-organic partitioning system was tested with this novel technique as well. Because of the rather low porosity of synthesized PANi membrane, such a system did not yield a high release rate. The transport rates through polymeric membrane alone were accurately predicted using simplified mass transport models for both iontophoretic and non-iontophoretic systems. Finally, a further application of this new technique was investigated using a thermo-sensitive TDD system. A hydrophilic porous PVDF membrane immobilized with a thermo-sensitive polymeric gel, poly(Nisopropylacrylamide) (PNIPAAM)-co-2mol% acrylic acid (AA), demonstrated its release-"on/off' switch function: at normal skin temperature, no release of doxycycline HCl through the skin occurred; under fever condition, certain amount of this antibiotic accumulated beneath the skin.

Share

COinS