Effect of vehicle upon in vitro transcorneal permeability and intracorneal content of ?9-tetrahydrocannabinol

Abstract

To determine the transcorneal flux, and intracorneal penetration, of Delta9-tetrahydrocannabinol when presented to the isolated rabbit cornea in different vehicles. Corneas were mounted in specular microscope chambers, with ( 3)H-Delta9-tetrahydrocannabinol on the epithelial surface in one of 15 vehicles and the endothelium perfused with Ringer. Following equilibration the perfusate was collected at 20 minute intervals and sampled for counting. After 3 hours the epithelium was harvested and the stroma/endothelium collected. The tissues were placed in distilled water and sampled at 24 hours. The order of efficacy of the best 6 vehicles in terms of transcorneal Delta9-tetrahydrocannabinol flux was: alpha-cyclodextrin > hydroxypropylmethylcellulose (80 to 120 centipoises)> polyvinyl alcohol > hydroxypropylmethylcellulose (3500 to 5600 centipoises)> polyvinylpyrrolidone (29 to 32 centipoises) > polyvinylpyrrolidone (12 to 18 centipoises). Remaining vehicles, including light mineral oil, corn oil, hyaluronic acid, hydroxypropyl-beta-, beta-, and gamma-cyclodextrin and hydroxypropylmethylcellulose (40 to 60 centipoises) all gave lower fluxes. The epithelium was the site of most intracorneal drug. Differentiation was made between several potential vehicles for in vivo topical delivery of Delta9-tetrahydrocannabinol. The vehicles include cyclodextrins and other excipients such as hydroxypropylmethylcellulose and polyvinylpyrrolidone. There is not a strong relationship between solubility or binding of the lipophilic drug by excipients and transcorneal flux. The most efficacious vehicles provided a considerably greater transcorneal drug flux than light mineral oil which previously had been shown to deliver sufficient topical Delta9-tetrahydrocannabinol to reduce intraocular pressure of several species. The new vehicles should permit greater pharmacological sequelae.