Date of Award
Ph.D. in Pharmaceutical Sciences
Michael A. Repka
University of Mississippi
Itraconazole is a broad-spectrum triazole antifungal agent used to prevent and treat fungal infections. Itraconazole is commercially available as an oral and intravenous formulation; however, its administration via these routes is associated with various side effects, such as hepatotoxicity, peripheral neuropathy, cardiac dysrhythmia, and hearing loss. Therefore, in this research, stable non-aqueous topical creams and gels loaded with itraconazole were investigated with the intent to prolong drug contact, improve drug permeation and penetration into skin layers, and overcome the side effects associated with other routes of administration for improved therapeutic outcomes. Chapter 1 discusses the development and characterization strategies during the development of the itraconazole non-aqueous creams while chapter 2 reports the preparation and optimization of the itraconazole non-aqueous gels. The lead cream formulation was stable over three months (the last time-point tested) during refrigeration and room-temperature storage. The cream formulation developed with 15% w/w Transcutol® P improved itraconazole permeation and deposition through the skin by 8.4- and 8.2-fold, compared to the drug solution, respectively. All lead gel formulations were found to have desirable physicochemical characteristics and showed three-month stability (the last time-point tested) during refrigeration, room temperature, and accelerated storage conditions. The gel formulation developed with 0.5% w/w Carbopol® 940 P improved itraconazole permeation and deposition through the skin by 5.1- and 6.8-fold, compared to the drug solution, respectively. Chapter 3 discusses the development and validation of HPLC method for the antifungal drug efinaconazole for application to human nail permeation studies. The developed method was validated as per FDA guidelines, and the results met the acceptance criteria. The method developed was specific, and the method was linear over the efinaconazole concentration range of 0.05 to 10 μg/mL (R2 ≥ 0.9981). In conclusion, the itraconazole-loaded non-aqueous creams and gels can serve as alternative drug delivery platforms for the treatment of fungal skin infections over oral/parenteral itraconazole formulations. Moreover, the developed efinaconazole HPLC method can be applied for formulation evaluation and clinical studies.
Kolimi, Praveen, "Developing Novel Topical Formulations for Azole drugs" (2023). Electronic Theses and Dissertations. 2531.