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Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins.
AAPS PharmSciTech 2011; 12(2):723-31AP

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.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, Oxford, 38677, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21637944

Citation

Hippalgaonkar, Ketan, et al. "Enhanced Solubility, Stability, and Transcorneal Permeability of Δ-8-tetrahydrocannabinol in the Presence of Cyclodextrins." AAPS PharmSciTech, vol. 12, no. 2, 2011, pp. 723-31.
Hippalgaonkar K, Gul W, ElSohly MA, et al. Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins. AAPS PharmSciTech. 2011;12(2):723-31.
Hippalgaonkar, K., Gul, W., ElSohly, M. A., Repka, M. A., & Majumdar, S. (2011). Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins. AAPS PharmSciTech, 12(2), pp. 723-31. doi:10.1208/s12249-011-9639-5.
Hippalgaonkar K, et al. Enhanced Solubility, Stability, and Transcorneal Permeability of Δ-8-tetrahydrocannabinol in the Presence of Cyclodextrins. AAPS PharmSciTech. 2011;12(2):723-31. PubMed PMID: 21637944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced solubility, stability, and transcorneal permeability of δ-8-tetrahydrocannabinol in the presence of cyclodextrins. AU - Hippalgaonkar,Ketan, AU - Gul,Waseem, AU - ElSohly,Mahmoud A, AU - Repka,Michael A, AU - Majumdar,Soumyajit, Y1 - 2011/06/03/ PY - 2011/01/27/received PY - 2011/05/23/accepted PY - 2011/6/4/entrez PY - 2011/6/4/pubmed PY - 2012/5/17/medline SP - 723 EP - 31 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 12 IS - 2 N2 - 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. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/21637944/Enhanced_solubility_stability_and_transcorneal_permeability_of_δ_8_tetrahydrocannabinol_in_the_presence_of_cyclodextrins_ L2 - https://dx.doi.org/10.1208/s12249-011-9639-5 DB - PRIME DP - Unbound Medicine ER -