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 (Ä(8)-THC). Phase solubility of Ä(8)-THC was studied in the presence of 2-hydroxypropyl-â-cyclodextrin (HPâCD), randomly methylated-â-cyclodextrin (RMâCD) and sulfobutyl ether-â-cyclodextrin sodium salt (SâCD). Stability of Ä(8)-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Ä(8)-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Ä(8)-THC in the presence of both HPâCD and RMâCD was of the A(P) type, whereas, with SâCD an A(L) type was apparent. Aqueous solubility of Ä(8)-THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HPâCD, RMâCD, and SâCD, respectively. Significant degradation of Ä(8)-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Ä(8)-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of Ä(8)-THC. Thus, topical ophthalmic formulations containing Ä(8)-THC and modified beta CDs may show markedly improved ocular bioavailability.
Administration, Topical Animals