Date of Award
1-1-2023
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Soumyajit Majumdar
Second Advisor
Michael A. Repka
Third Advisor
Dr. Walter Chambliss
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Microbial keratitis, if not treated in time, can exacerbate critical conditions and ultimately lead to loss of vision. Incidences of bacterial and fungal keratitis in developing countries are far more compared to developed nations due to socioeconomic and environmental factors. Many regions of these developing countries might have limited resources to identify the causative agent in time, and accurately, before choosing appropriate treatment. In cases of such infections, empiric therapy is typically commenced with topical antibacterial for bacterial infections and antifungal for fungal keratitis. Moxifloxacin (MOX) is a fourth-generation antibacterial drug effective against both gram-positive and gram-negative bacteria. Voriconazole (VORI), is a second-generation triazole that has wider antifungal activity than other triazoles. The objective of this study was to fabricate and evaluate dual drug-loaded ophthalmic inserts containing 0.5mg MOX and 1mg of VORI, containing an antibacterial and antifungal drug to better manage ocular keratitis in regions where resources for the identification of microbe are limited. Inserts fabricated using the melt cast technique have been examined for drug content, surface pH, swelling index, moisture absorption, and moisture loss. The in vitro release showed a sustained release of up to six hours for both drugs with 40% (w/w) PLGA in the formulation. Interestingly, it was observed that MOX-only inserts showed an extended release of 24 hours whereas VORI-only inserts show an extended release for 6 hours, similar to that of the combination product. The ex vivo trans-corneal permeation studies were performed and compared against commercial MOX eye drops and VORI solution. The lower trans-corneal flux from the inserts for both drugs, compared to solution controls, is consistent with the extended release pattern observed. The SEM images showed a smooth surface for all fabricated inserts indicating less chance of ocular irritation. The physio-chemical characteristics and drug content for these inserts remained unchanged after a period of three months (last time point checked). In conclusion, the results indicate that the ophthalmic inserts present a promising drug delivery platform to better manage ocular keratitis.
Recommended Citation
Pendse, Jui, "Fabrication and Evaluation of a Dual-Drug Loaded Immediate and Sustained Release Ophthalmic Inserts for the Management of Keratitis; Moxifloxacin and Voriconazole" (2023). Electronic Theses and Dissertations. 2561.
https://egrove.olemiss.edu/etd/2561