Date of Award
M.S. in Pharmaceutical Science
Michael A. Repka
University of Mississippi
The objective of this investigation was to formulate, characterize, and evaluate a bioadhesive, hot-melt extruded (HME), immediate- and extended-release ophthalmic inserts containing a fixed-dose combination of Prednisolone Sodium Phosphate (PSP) and Sulfacetamide Sodium (SA) to improve the treatment outcomes of multiple ocular bacterial infections. The HME inserts were prepared using FDA-authorized biocompatible polymers including Polyox WSR N10 LEO NF (polyethylene oxide; PEO), Klucel™ HF (hydroxypropyl cellulose; HPC-HF), and Ethocel™ (Ethylcellulose; EC). The inserts were then assessed for physicochemical characteristics, weight variation, surface pH, uniformity of thickness, drug content, swelling index, thermal analysis, drug–excipient compatibility, moisture uptake and loss, surface morphology, mucoadhesive strength, in vitro release, ex-vivo transcorneal permeation and deposition, and stability. The HPC-HF and EC-containing inserts extended the release of both drugs compared to PEO-N10-based inserts that showed the release of the loaded amount of both drugs immediately (< 1 h). All fabricated inserts were stable over 90-day storage at room temperature (25ºC) and accelerated conditions (40ºC) for drug content, and thermal behavior. The developed PSP-SA inserts exhibited optimum bioadhesive strength and smooth surface favorable for topical ocular application. Ex vivo transcorneal permeation studies using freshly isolated rabbit corneas demonstrated that the extended-release inserts slowed down the transcorneal flux of the drug in comparison to the immediate-release inserts and the commercial solution eyedrops. Overall, the inserts were fabricated using a solvent-free, scalable, and continuous manufacturing process and could reduce the frequency of administration to once-daily application, affording a new topical delivery vehicle with prolonged antibacterial and anti-inflammatory activity during ocular bacterial infections treatment.
Karnik, Indrajeet, "Formulation Development and Characterization of Dual Drug Loaded Hot-Melt Extruded Inserts for Better Ocular Therapeutic Outcomes: Sulfacetamide/Prednisolone" (2023). Electronic Theses and Dissertations. 2529.
Available for download on Friday, September 13, 2024