Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye

Eva Ramsay, Eva M Del Amo, Elisa Toropainen, Unni Tengvall-Unadike, Veli-Pekka Ranta, Arto Urtti, Marika Ruponen

Research output: Contribution to journalArticlepeer-review

Abstract

On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70 × 10-6 cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be <5% and trans-conjunctival systemic absorption was 34-79% of the dose. Loss of drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Volume119
Early online date3 Apr 2018
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • Animals
  • Aqueous Humor/metabolism
  • Biological Availability
  • Conjunctiva/blood supply
  • Cornea/metabolism
  • Permeability
  • Pharmaceutical Preparations/metabolism
  • Quantitative Structure-Activity Relationship
  • Regional Blood Flow
  • Swine

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