Electronic Theses and Dissertations

Title

Biophysical Techniques of Transcutaneous Drug Sampling and Drug Delivery

Date of Award

2011

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Narasimha S. Murthy

Second Advisor

John S. Williamson

Third Advisor

Seongbong Jo

Abstract

Monitoring the time course of drug in the skin is critical for determining the frequency and dose of drug administration from safety and efficacy perspectives. Intermittent blood sampling is used as a surrogate for approximating concentration of drugs in the tissues, which leads to blood loss and discomfort to patients. A novel noninvasive technique called “Electroporation and transcutaneous sampling” (ETS) was developed for estimating the drug concentration in the skin extracellular fluid. The application of ETS technique in studying dermatokinetics of cephalexin, ciprofloxacin, and 8-methoxypsoralen was investigated. The results demonstrated the ability of ETS technique in dermatokinetic studies of drugs with different physicochemical properties. ETS technique was also found to be a promising method for noninvasive estimation of blood glucose levels. Two novel techniques were developed for enhancing the transdermal delivery of drugs. “ChilDrive”, a technique of combining regional cutaneous hypothermia with iontophoresis was used for enhancing the bioavailability of transdermally administered drug in the deeper musculoskeletal tissue like synovial fluid. The bioavailability of drugs in the synovial fluid of knee joint was enhanced by ?6-12-fold and ?2-4-fold by ChilDrive when compared to passive and iontophoretic transdermal drug delivery. Magnetophoresis, a technique of enhancing transdermal drug delivery by application of magnetic field was developed. The mechanistic studies demonstrated that transdermal magnetophoresis of drugs was due to contribution of multiple factors such as magnetorepulsion, magnetohydrokinesis and magnetically enhanced partition coefficient. Magnetophoretic patch system was designed and pharmacokinetic studies were performed. Magnetophoresis resulted in higher dermal bioavailability of drugs compared to passive transdermal drug delivery. It was also found from the in vitro studies that combination of chemical enhancers would further enhance the efficiency of magnetophoretically mediated drug delivery enhancement.

Concentration/Emphasis

Pharmaceutics

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