Date of Award
Ph.D. in Pharmaceutical Sciences
Michael A. Repka
University of Mississippi
Gatifloxacin (GTX) is a broad-spectrum 4th generation antimicrobial fluroquinolone used in the treatment of ocular infections such as conjunctivitis, keratitis and keratoconjuctivitis. GTX (as a sesquihydrate) is commercially available as aqueous eyedrops for the treatment of bacterial conjunctivitis (BC) which requires frequent administration due to low residence time on the conjunctival surface. The eye is a highly specialized photoreceptive organ, which is protected by a continuous tear flow containing antibacterial components. However, inflammation or scarring of the eye may be difficult to resolve once having occurred. Furthermore, initial infections if ignored are likely to invade the inner portions of the eye and/or spread to the adjacent structures, even leading to blindness in some cases. Due to the eye’s protective mechanism; the bioavailability and by extension the efficacy of the active drug is limited due to the highly impermeable environment of the ocular surface leading to frequent administration. Despite these shortcomings, topical drug delivery systems are the most preferred route, with about 90% of marketed dosage forms being eyedrops.
The aim of this study was to explore different lipid-based drug delivery systems to overcome the limitations of the commercial GTX formulation and to better the treatment of BC. GTX loaded NEs were formulated via Hot melt extrusion (HME) coupled with probe sonication and GTX loaded SLNs and NLCs were developed using different excipients in the formulation design.
Nanoemulsions (NEs) are well developed and stable colloidal dispersions. These emulsions serve as a drug depot by interacting with the lipids present on the ocular surface thereby enhancing ocular bioavailability of the active drug. GTX loaded NEs were prepared using HME coupled with probe sonication and by the conventional method of hot homogenization followed by probe sonication. A three-month stability (physical and chemical), in vitro release, ex vivo permeation, and in vitro cytotoxicity were evaluated for the lead formulations.
GTX loaded SLNs and NLCs were formulated via the hot homogenization technique. The effect of various lipid and surfactant concentration on the characteristics of the formulation were investigated. The lead NLC formulation demonstrated an extended GTX release profile with the MIC90 being achieved within the first time point. The ex vivo studies showed a 6-fold increase in permeability compared to the commercial formulation. Furthermore, the lead NLC was physiochemically stable over three months even at elevated storage conditions.
In conclusion, lipid-based drug delivery systems can be efficient topical drug delivery systems. Eyedrops formulated as such could potentially improve treatment outcomes while also reducing the dosing frequency and increasing patient compliance.
Joshi, Poorva Hemant, "Sustained and Improved Ophthalmic Formulations of Gatifloxacin for Better Therapeutic Outcomes During Topical Ocular Applications" (2023). Electronic Theses and Dissertations. 2526.
Available for download on Friday, September 13, 2024