title: Ocular disposition of the hemiglutarate ester prodrug of ∆⁹-Tetrahydrocannabinol from various ophthalmic formulations.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.
authors.forename: Tushar
authors.initials: T
authors.lastname: Hingorani
authors.forename: Goutham R
authors.initials: GR
authors.lastname: Adelli
authors.forename: Nagendra
authors.initials: N
authors.lastname: Punyamurthula
authors.forename: Waseem
authors.initials: W
authors.lastname: Gul
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Elsohly
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D060433:Administration, Ophthalmic; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D013759:Dronabinol / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005123:Eye / Q000378:metabolism*; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D014677:Pharmaceutical Vehicles; D011355:Prodrugs; D013501:Surface-Active Agents; D013759:Dronabinol