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Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations

Abstract

The purposes of this project are to enhance the trans-membrane penetration of Δ8-Tetrahydrocannabinol (Δ8-THC) and to study the effect of various lipid based systems in delivering the compound, non-invasively, to anterior and posterior ocular chambers. Solid lipid nanoparticles (SLNs), fast gelling films were manufactured using high pressure homogenization and melt cast techniques, respectively. The formulations were characterized for drug content, entrapment efficiency, particle size and subsequently evaluated in vitro for trans-corneal permeation. In vivo, the drug disposition was tested via topical administration in albino rabbits. The eye globes were enucleated at the end of experiment and tissues were analyzed for drug content. All formulations showed favorable physicochemical characteristics in terms of particle size, entrapment efficiency, and drug content. In vitro, the formulations exhibited a transcorneal flux that depended on the formulation’s drug load. An increase in drug load from 0.1 to 0.75% resulted in 12- to16-folds increase in permeation. In vivo, the film was able to deliver THC to all the tissues with high accumulations in cornea and sclera. The SLNs showed a greater ability in delivering THC to all the tissues, at a significantly lower drug load, due to their colloidal size range, which in turn enhanced corneal epithelial membrane penetration. The topical formulations evaluated in the present study were able to successfully deliver Δ8-THC in therapeutically meaningful concentrations (EC50 values for CB1: 6 nM and CB2: 0.4 nM) to all ocular tissues except the vitreous humor, with pronounced tissue penetration achieved using SLNs as a Δ8-THC delivery vehicle.

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Acknowledgments

This publication was made possible by Grant Number P20GM104932 from the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health (NIH).

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Correspondence to Soumyajit Majumdar.

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Punyamurthula, N.S., Adelli, G.R., Gul, W. et al. Ocular Disposition of ∆8-Tetrahydrocannabinol from Various Topical Ophthalmic Formulations. AAPS PharmSciTech 18, 1936–1945 (2017). https://doi.org/10.1208/s12249-016-0672-2

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  • DOI: https://doi.org/10.1208/s12249-016-0672-2

KEY WORDS

  • lipid-based drug delivery
  • ocular drug delivery
  • ocular films
  • solid lipid nanoparticles
  • tetrahydrocannabinol