Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Soumyajit Majumdar

Second Advisor

Samir A. Ross

Third Advisor

Michael A. Repka


University of Mississippi

Relational Format



Natamycin (NT) is a front-line drug in the management of ocular fungal infections (OFI). An ophthalmic marketed NT suspension (Natacyn®) is currently the only FDA approved medication prescribed in the pharmacotherapy of OFI. Current NT pharmacotherapy requires frequent topical administration (every hour or 2-hours over 6-8 times in a day) due to it being instilled as eye-drops. This leads to higher precorneal losses and subsequent poor permeation and bioavailability. Therefore, in this research study, alternative ocular formulations of NT were investigated with an intent to improve precorneal retention and corneal permeation in comparison to Natacyn®. Chapter 1 discusses various aspects of NT such as its chemistry and pharmacology, antifungal spectrum and potential for development of resistance, ocular clinical evaluations, and specifics on Natacyn® to obtain a perspective of NT use in OFI. Chapter 2 reports the preparation and optimization of NT loaded surface coated PEGylated NLC (NT-PEG-NLC) using Box-Behnken Design. The optimized NT-PEG-NLC were found to have desirable physicochemical characteristics and exhibited significantly higher transcorneal permeation than Natacyn®, in vitro. In vivo ocular biodistribution of NT-PEG-NLC indicated that, despite NT load in NT-PEG-NLC (0.3%) being 1/16th of Natacyn® (5%), NT-PEG-NLC permeated the intact cornea to reach the inner tissues. To further improve ocular delivery of NT, chapter 3 reports on the development of a gelling system using a full factorial design in which the optimized NT-PEG-NLCs were loaded. This gelling system at a lower NT concentration (0.3%) compared to Natacyn® (5%), displayed superior pharmacokinetic parameters in the tear film and comparable NT concentrations in the inner ocular tissues (in vivo) at a 16-fold lower dose; indicating its potential ocular applications. Chapter 4 reports on the design of Eudragit™ RLPO based ocular films for ocular delivery of NT using central composite design. An optimized film formulation was selected on the bases of the interaction plots between the independent factors and dependent variables; and, it exhibited significantly higher transcorneal permeation (ex vivo) and superior pharmacokinetic parameters (in vivo) compared to Natacyn®. These observations imply that, NT-loaded films could also be explored as alternative dosage forms in the management of OFI.



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