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Theoretical corneal permeation model for ionizable drugs
S W Friedrich1, Y L Cheng, B A Saville
1Department of Chemical Engineering and Applied Chemistry, University of Toronto, Canada.
Journal of Ocular Pharmacology
|January 1, 1993
Summary
A new eye drug model reveals that drug ionization equilibrium significantly impacts ocular bioavailability, increasing aqueous humor drug levels over 50-fold. This enhances understanding of transcorneal permeation for improved drug delivery.
Area of Science:
- Ocular drug delivery
- Pharmacokinetics
- Biomedical modeling
Background:
- Transcorneal permeation is the primary ocular drug route.
- Understanding these mechanisms can improve drug bioavailability and delivery devices.
Purpose of the Study:
- To develop and validate a multi-compartment model simulating transcorneal drug permeation.
- To investigate the influence of drug ionization equilibrium on ocular drug concentrations.
Main Methods:
- A five-compartment model (tear film, epithelium, stroma, endothelium, aqueous humor) was developed.
- Simulated drug loss via lacrimal drainage, conjunctival absorption, aqueous drainage, and iris-ciliary body absorption.
- Incorporated drug lipophilicity and ionization equilibrium for permeability calculations.
Main Results:
- Including ionization equilibrium increased predicted aqueous humor drug levels by over 50-fold compared to models without it.
- The model accurately predicted in vivo aqueous humor drug concentrations for timolol, levobunolol, and pilocarpine.
- Quantified drug loss through major ocular elimination routes.
Conclusions:
- Drug ionization equilibrium is a critical factor in transcorneal permeation and ocular drug bioavailability.
- The developed model provides a valuable tool for predicting ocular drug disposition and optimizing ophthalmic formulations.