Dose Uniformity of Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38% Compared with Prednisolone Acetate Ophthalmic Suspension 1

Introduction Loteprednol etabonate (submicron) ophthalmic gel 0.38% (LE SM gel 0.38%) is a corticosteroid formulation designed to retain the nonsettling characteristics of loteprednol etabonate ophthalmic gel 0.5%, but with reduced drug particle size to improve ocular penetration, allowing for reduced dosing frequency. This study compared the dose uniformity of LE SM gel 0.38% with branded and generic prednisolone acetate (PA) 1% suspensions under simulated in-use dosing conditions. Methods Drug concentrations in drops of LE SM gel 0.38% and PA 1% suspensions, expressed from bottles that were shaken or not shaken, were determined during 2 weeks of simulated on-label dosing (LE SM gel 0.38%: three times daily; PA suspensions: four times daily). Sedimentation of drug particles was assessed for each product using dispersion analysis. Results The mean (SD) percent declared drug concentration of LE SM gel 0.38% over 2 weeks was 103.2% (1.3%) when the drug was dispensed from shaken bottles and 103.3% (1.5%) when dispensed from unshaken bottles. However, for branded and generic PA suspensions, mean (SD) percent declared concentrations were 102.2% (1.4%) and 98.3% (2.9%), respectively, when dispensed from shaken bottles; and 89.2% (18.6%) and 78.3% (13.5%), respectively, when dispensed from unshaken bottles. Dispersion analysis showed that drug particles in LE SM gel 0.38% remained fully suspended under accelerated sedimentation conditions, whereas both branded and generic PA suspension drug particles settled out of suspension. Conclusions LE SM gel 0.38% delivered the drug consistently at the declared concentration over the entire 2 weeks of simulated in-use dosing conditions, regardless of whether the drug was dispensed from shaken or unshaken bottles. However, both branded and generic PA suspensions required the bottle to be shaken to provide a consistent drug concentration.