Corneal Permeability of Pilocarpine HCl 1.25% with Varying pH Formulations

Abstract

Purpose : Evaluate the in vitro corneal permeability of Pilocarpine HCl 1.25% with varying pH formulations.

Methods : Cornea permeability was assessed using Lonza Human Corneal Epithelial Cells (HCEC) grown in a 24-well Transwell cell culture insert. The permeability of 5 formulations of Pilocarpine HCl 1.25% topical solution with varying pH levels (pH = 4.3, 5.1, 6.06, 7.16, and 7.96) were examined.

Results : Mean Apparent Permeability (P_app) increased as pH increased (0.330, 0.431, 1.19, 0.670, 5.03, 7.02 x 10^-6 cm/s) with a dramatic increase in pH above 7 (Figure 1). A significant decrease in Transepithelial Electrical Resistance (TEER) values at 120 minutes was observed compared with baseline for all tested formulations except mannitol control. Despite this decrease, limited permeability of the lower pH formulations suggest that the barrier function of the cell layers was not compromised during the study.

Conclusions : The increase in permeability from pH 4.3 to pH 7.96 may be attributed to increasing un-ionized form of pilocarpine (~0.07% un-ionized at pH 4.3 vs. ~87.6% un-ionized at pH 7.96) in the formulation, as permeability across corneal epithelial layers favor un-ionized molecules. Increased permeability could translate into higher levels of pilocarpine in the anterior chamber and greater or longer activation of the iris sphincter and/or ciliary muscle, the target tissues of Pilocarpine HCl 1.25% to induce the pinhole effect and increase depth of focus.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1