Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins

AAPS PharmSciTech. 2011 Jun;12(2):723-31. doi: 10.1208/s12249-011-9639-5. Epub 2011 Jun 3.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Animals
  • Cornea / drug effects
  • Cornea / metabolism*
  • Cyclodextrins / administration & dosage
  • Cyclodextrins / chemistry
  • Cyclodextrins / pharmacokinetics*
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / chemistry
  • Dronabinol / pharmacokinetics
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Drug Stability
  • Male
  • Permeability
  • Rabbits
  • Solubility

Substances

  • Cyclodextrins
  • Drug Carriers
  • delta-8-tetrahydrocannabinol
  • Dronabinol