Abstract
Purpose :
We previously reported a non-compartmental pharmacokinetic model for transcorneal penetration of rhodamine B (RhB), which was used as a fluorescent surrogate for topical lipophilic drugs (Pharm Res, 2010. 27(4): p. 699-711). In this study, we simulate the model using the versatile finite element method (FEM) to predict transcorneal and anterior chamber (a/c) kinetics of topical lipophilic solutes (LS).
Methods :
Once administered, the concentration of LS at the ocular surface is assumed to follow transient kinetics with a half-life of 3 min, typical of topical agents in humans. During its presence on the ocular surface, LS is modeled to penetrate the cornea by a partition-diffusion mechanism. In particular, we suppose partitioning of LS from the tears across the cornea, layer-by-layer, and further by diffusion in each layer. Moreover, we assume linear equilibrium binding of LS in the epithelium and continuity of flux at the interfacial boundaries. The resulting partial differential equations were solved by FEM in Comsol™.
Results :
Following a topical drop, LS showed prominent transient accumulation in the epithelium and endothelium, leading to a diffusive gradient in the stroma and flux into the a/c (Fig. 1). The concentration profile showed strong discontinuities at the epithelium-stroma and stroma-endothelial boundaries consistent with our experimental findings (Pharm Res, 2010. 27(4): p. 699-711). The computed concentration profile in the a/c showed a peak at ~90 min (inset in Fig. 1) but was faster when the diffusion coefficient of LS in the different layers was increased. When the partition coefficient was raised by order of magnitude, the accumulation in epithelium and flux across the cornea increased.
Conclusions :
We have developed a general FEM-based approach to solve the diffusion kinetics of topical lipophilic drugs and tested the model for lipophilic agents.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.