Abstract
Purpose :
Dose uniformity can be challenging with ophthalmic suspensions since drug particles may settle over time and patients often fail to adequately shake the bottle prior to instillation. Loteprednol etabonate (submicron) ophthalmic gel 0.38% (LE gel 0.38%) is a polycarbophil-based formulation that is a semi-solid at rest to prevent drug particle settling. This study compared dose uniformity of LE gel 0.38% and prednisolone acetate (PA) 1% suspensions under shaken and unshaken simulated in-use conditions.
Methods :
One set of 5 mL bottles of LE gel 0.38% and branded and generic PA suspensions was shaken for 5 seconds immediately prior to drop expression at simulated dosing time points over two weeks, whilst a second set of bottles was not shaken prior to drop expression. The dispensing time points followed product label recommendations: LE gel 0.38% was dispensed three times daily (7 AM, 12 PM, and 10 PM, ± 1 h), while PA suspensions were dispensed four times daily (7 AM, 12 PM, 5 PM and 10 PM, ± 1 h). The first and last daily dispensed drops were collected and drug concentrations analyzed by high pressure liquid chromatography. Data were expressed as mean ± SD percent of the declared (labeled) concentration for each drug.
Results :
Dispensed drops of LE gel 0.38% showed consistent on-target mean drug concentrations over 2 weeks of dosing whether expressed from shaken (103.2 ± 1.3%) or unshaken (103.3 ± 1.5%) bottles. In contrast, while mean drug concentrations for both branded and generic PA suspensions were on-target over 2 weeks of dosing following expression from shaken bottles (102.2 ± 1.39% and 98.3 ± 2.87%, respectively), they were highly variable over the two weeks when dispensed from unshaken bottles (89.2 ± 18.59% and 78.3 ± 13.47%, respectively). Drug concentrations of dispensed PA drops from unshaken bottles were lowest at the start of the study and were outside of 90-110% of the declared concentration for the majority of dispensed drops over the 2 weeks.
Conclusions :
Drops of LE gel 0.38% delivered the declared concentration of LE under both shaken and unshaken simulated in-use conditions whereas drops of PA 1% suspensions were on-target when shaken, but highly variable when the bottles were not shaken. LE gel 0.38% is expected to provide consistent dosing and therefore consistent efficacy over the entire 2 week dosing regimen regardless of shaking.
This is a 2021 ARVO Annual Meeting abstract.