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.