Abstract
Purpose :
This study aims to investigate the feasibility and effectiveness of delivering an active pharmaceutical ingredient (API) to intraocular tissues through topical cream administration onto ex vivo rabbit eyelids.
Methods :
Ex vivo rabbit eyelids were topically dosed with an ophthalmic cream, followed by incubation at 37°C and near 100% relative humidity for 4 or 24 hrs. The aqueous humor (AH) and iris-ciliary body (ICB) were collected to quantify API permeation using LC-MS. The API concentration was normalized to extraction volume or tissue mass. API extraction yields from the ICB were compared between homogenization and enzymatic digestion methods. One-way ANOVA was used for data analysis.
Results :
The formulation was a smooth cream with specified pH and viscosity. To optimize the API extraction method, ICBs were dissected from eyes dosed with a total of 100 mg cream for 24 hrs. One half of each ICB was subjected to physical homogenization, while the other half was subjected to enzymatic digestion. Similar API yields were obtained using physical homogenization (130.8±104.6 ng/mg) or enzymatic digestion (133.1±98.2 ng/mg). To investigate the effect of dosage on API permeation, API concentrations in the ICB and in the AH were studied for various treatment regimens. The results showed that while API levels in the ICB of eyes dosed with 50 mg cream for 4 hrs (44±30 ng/mg) were similar to those dosed with 100 mg for 4 hrs (75±72 ng/mg), API levels increased significantly in eyes applied with a repeated 4 hr dose of 50 mg at 20 hrs post initial dosing (197.9±159.8 ng/mg) (p = 0.0004). Similarly, API levels in the AH of eyes with the repeated 50 mg dosing (70781±24676 ng/mL) were significantly higher than those dosed with 50 mg (11551±28213 ng/mL) or 100 mg (23677±32061 ng/mL) of cream for 4 hrs (p = 0.0006).
Conclusions :
We concluded that the ophthalmic cream applied to the eyelids can effectively deliver drug, not only to the ocular surface, but also to the intraocular structures in the anterior chamber. Repeat dosing further increased drug concentration in the target tissue, potentially resulting in improved efficacy and bioavailability.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.