Ocular disposition of the hemiglutarate ester prodrug of ∆⁹-Tetrahydrocannabinol from various ophthalmic formulations.

PURPOSE

The overall goal of this project is to enhance ocular delivery of ∆(9)-Tetrahydrocannabinol (THC) through the topical route.

METHODS

Solubility, stability and in vitro transcorneal permeability of the relatively hydrophilic hemiglutarate ester derivative, THC-HG, was studied in the presence of surfactants. The solutions were characterized with respect to micelle size, zeta potential and solution viscosity. In vivo studies were carried out in New Zealand albino rabbits. A previously reported promising THC-HG ion-pair formulation was also studied in vivo.

RESULTS

Aqueous solubility and stability and in vitro transcorneal permeability of THC-HG was enhanced significantly in the presence of surfactants. THC levels in the ocular tissues (except cornea) were found to be below detection limits from mineral oil, surfactant or emulsion based formulations containing THC. In contrast, micellar and ion pair based THC-HG formulations produced significantly higher total THC concentrations in the anterior ocular chamber.

CONCLUSION

In this study, although delivery of THC to the anterior chamber ocular tissues could be significantly increased through the prodrug and formulation approaches tested, further studies are needed to increase penetration to the back-of-the eye.