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Abstract #46186 Published in IGR 13-2
Enhanced Solubility, Stability, and Transcorneal Permeability of Delta-8-Tetrahydrocannabinol in the Presence of Cyclodextrins
Hippalgaonkar K; Gul W; Elsohly MA; Repka MA; Majumdar SAAPS PharmSciTech 2011;
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 ((Delta)(8)-THC). Phase solubility of (Delta)(8)-THC was studied in the presence of 2-hydroxypropyl-(beta)-cyclodextrin (HP(beta)CD), randomly methylated-(beta)-cyclodextrin (RM(beta)CD) and sulfobutyl ether-(beta)-cyclodextrin sodium salt (S(beta)CD). Stability of (Delta)(8)-THC in 5% w/v aqueous CD solutions, as a function of pH, was studied following standard protocols. In vitro corneal permeation of (Delta)(8)-THC (with and without CDs) across excised rabbit cornea was also determined. Phase-solubility profile of (Delta)(8)-THC in the presence of both HP(beta)CD and RM(beta)CD was of the A(P) type, whereas, with S(beta)CD an A(L) type was apparent. Aqueous solubility of (Delta)(8)-THC increased to 1.65, 2.4, and 0.64 mg/mL in the presence of 25% w/v HP(beta)CD, RM(beta)CD, and S(beta)CD, respectively. Significant degradation of (Delta)(8)-THC was not observed within the study period at the pH values studied, except for at pH 1.2. Transcorneal permeation of (Delta)(8)-THC was dramatically improved in the presence of CDs. The results demonstrate that CDs significantly increase aqueous solubility, stability, and transcorneal permeation of (Delta)(8)-THC. Thus, topical ophthalmic formulations containing (Delta)(8)-THC and modified beta CDs may show markedly improved ocular bioavailability.
S. Majumdar. Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, 111 Faser Hall, Oxford, 38677, Mississippi, United States. Email: majumso@olemiss.edu
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
