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 (Δ8-THC). Phase solubility of Δ8-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 Δ8-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of Δ8-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of Δ8-THC in the presence of both HPβCD and RMβCD was of the AP type, whereas, with SβCD an AL type was apparent. Aqueous solubility of Δ8-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 Δ8-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of Δ8-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of Δ8-THC. Thus, topical ophthalmic formulations containing Δ8-THC and modified beta CDs may show markedly improved ocular bioavailability.
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The project was partially supported by grant numbers 5P20RR021929 from the National Center for Research Resources and 1R41EY020042-01A1 from the National Eye Institute (NEI), National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or NEI.
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Hippalgaonkar, K., Gul, W., ElSohly, M.A. et al. Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins. AAPS PharmSciTech 12, 723–731 (2011). https://doi.org/10.1208/s12249-011-9639-5