Fixed combination aids drug delivery, enhances ocular surface retention

Key Points

Norfolk, VA-A new formulation of a fixed antibiotic/corticosteroid combination containing tobramycin and dexamethasone offers several improved characteristics that make it a viable therapeutic option for the management of inflammatory ocular conditions where a risk of bacterial ocular infection exists, said Stephen V. Scoper, MD.

Dr. Scoper was an investigator in a clinical trial evaluating the new fixed combination and the lead author of a published paper [Adv Ther. 2008;25:77-88] reporting on that study and several in vitro and animal investigations. He is vice president, Virginia Eye Consultants, and associate professor of ophthalmology, Eastern Virginia Medical School, Norfolk.

Overall, the research evidence showed that compared with the original formulation containing tobramycin 0.3%/dexamethasone 0.1% (TobraDex, Alcon Laboratories), the new product exhibits better suspension formulation characteristics and ocular bioavailability.

In addition, the higher concentrations of antibiotic achieved in ocular tissues using the new tobramycin/dexamethasone formulation translate into improved antibacterial activity against tobramycin-resistant and methicillin-resistant strains of two common ocular pathogens.

"TobraDex has been the most widely prescribed steroid/antibiotic ophthalmic combination product and is highly effective," he said.

However, the new product represents an improved formulation with a number of benefits that should increase its activity in the treatment and prevention of inflammation and bacterial infections, he said.

"It was very exciting to be involved in the clinical research and the publication for what I consider to be a great new product," Dr. Scoper said. "In particular, I am looking forward to using TOBRADEX ST for the treatment of blepharitis, a condition that I am affected by myself, because of its promise for addressing the challenge of achieving adequate drug concentrations in lid tissue."

Pharmaceutical innovation

The new formulation of tobramycin/dexamethasone contains pharmaceutical-grade xanthan gum that helps to prevent settling of active ingredient and imparts improved viscosity characteristics.

In the container, ionic interaction between xanthan gum and tobramycin results in lower viscosity and reduced settling of dexamethasone particles. Following instillation, the ionic interactions are disrupted because of the pH and ionic content of the tear film, resulting in a seven-fold increase in viscosity of the dispensed drop.

"On the ocular surface, the viscosity of the new formulation is about 80-fold higher than that of the original formulation, which results in improved retention on the ocular surface and greater ocular bioavailability," Dr. Scoper said.

The safety and tolerability profile also are comparable to the original formulation.

Testing of suspension-settling was performed by dispensing a series of 40-ml samples of the original and enhanced products and analyzing dexamethasone concentration in aliquots of the top 10 ml collected at various timepoints. In product allowed to sit for 24 hours, there was only 3% settling of dexamethasone in the new formulation compared with 61% settling in the original version.

Settling also was assessed in a study measuring dexamethasone concentration in suspension dispensed from product containers after they were shaken vigorously and stood upright for 24 hours. Without further shaking, the concentration of dexamethasone dispensed from the new formulation was 102% of the labeled concentration, compared with only 24% in testing the original product. The latter formulation needed to be shaken for 15 seconds to suspend dexamethasone particles adequately so that the dispensed concentration would equal the labeled amount, Dr. Scoper said.

"[Eye-care professionals] understand the importance of shaking the bottle vigorously with suspension formulations such as for typical steroid drops but also [understand] that patients don't always shake the bottle as directed and therefore may not get drug delivered at a therapeutic concentration," he said. "With TOBRADEX ST, I have the assurance that patients receive drug at the recommended and necessary concentration."