Transdermal Iontophoretic Delivery Of Lipophilic Drugs

Iontophoresis is one of the most widely studied active technique for enhancing transdermal delivery of drugs. However, its ability to enhance the delivery of highly lipophilic compounds is poor due to lack of any charge and poor water solubility of molecules. Propofol, a sedative and anesthetic drug was chosen as a one of the model lipophilic drug in this study. Initially, feasibility of delivery of propofol phosphate, a water soluble prodrug of propofol, via transdermal route using iontophoresis in combination with chemical permeation enhancers was investigated. Cathodal iontophoresis in combination with 0.1% sodium dodecyl sulphate synergistically enhanced the flux of propofol phosphate. The Pharmacokinetic studies were performed in rat model and the results suggest the plausibility of achieving therapeutically relevant levels of propofol when delivered via transdermal route. However, the pharmacodynamics studies revealed that propofol phosphate would be required at ∼10X the dose of propofol likely due to hydrophilicity and poor distribution into the brain. Therefore, it is crucial to discover approaches that would enhance the transdermal delivery of propofol in its parent form. The objective of using iontophoresis is to eventually utilize the feasibility of the technology to develop a programmable transdermal drug delivery system. Thus, transdermal delivery of propofol was studied by complexing with sulfobutyl ether-β-cyclodextrin (Captisol® CAP), a β-cyclodextrin derivative carrying ionizable groups to render propofol amenable to iontophoresis. The passive permeation flux of propofol was enhanced by four fold due to complexation with CAP. Application of iontophoresis (0.5 mA/cm2) to CAP-propofol solution enhanced the transport of propofol by an additional four fold. Pharmacokinetic studies shoa significant enhancement in the bioavailability of propofol when delivery in the form of complex by iontophoresis. Further, in vitro transport studies carried out using ibuprofen and testosterone demonstrated the potential of CAP as transport enhancer for lipophilic drugs. From the mechanistic studies, the enhancement in the transport of lipophilic drugs after complexation was found to be due to multiple mechanisms such as transport of intact complex, enhanced thermodynamic activity of drug at the interface and prolonged recovery of barrier disrupted due to iontophoresis.

Name thesis:degree_name

Ph.D. in Pharmaceutical Sciences

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Pharmaceutics and Drug Delivery

Year dc:date.available

2015

Author dc:creator

• Juluri, Abhishek

Contributors dc:contributor

• Narasimha S. Murthy
• N. P. Dhammika Nanayakkara
• Seongbong Jo

• Captisol
• Drug Delivery
• Iontophoresis
• Lipophilic
• Transdermal
• Transport Enhancer
• Pharmacy and Pharmaceutical Sciences

Repository record dc:identifier

https://egrove.olemiss.edu/etd/721

OAI identifier oai:identifier

oai:egrove.olemiss.edu:etd-1720