title: Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins.
abstract: The purpose of this study was to investigate the effect of cyclodextrins (CDs) on aqueous solubility, stability, and in vitro corneal permeability of delta-8-tetrahydrocannabinol (Δ(8)-THC). Phase solubility of Δ(8)-THC was studied in the presence of 2-hydroxypropyl-β-cyclodextrin (HPβCD), randomly methylated-β-cyclodextrin (RMβCD) and sulfobutyl ether-β-cyclodextrin sodium salt (SβCD). Stability of Δ(8)-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Δ(8)-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Δ(8)-THC in the presence of both HPβCD and RMβCD was of the A(P) type, whereas, with SβCD an A(L) type was apparent. Aqueous solubility of Δ(8)-THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HPβCD, RMβCD, and SβCD, respectively. Significant degradation of Δ(8)-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Δ(8)-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of Δ(8)-THC. Thus, topical ophthalmic formulations containing Δ(8)-THC and modified beta CDs may show markedly improved ocular bioavailability.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, Oxford, 38677, USA.
authors.forename: Ketan
authors.initials: K
authors.lastname: Hippalgaonkar
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: D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D008297:Male; D010539:Permeability; D011817:Rabbits; D012995:Solubility
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; C035731:delta-8-tetrahydrocannabinol; D013759:Dronabinol