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Effect of ion pairing on in vitro transcorneal permeability of a Δ(9) -tetrahydrocannabinol prodrug: potential in glaucoma therapy.
J Pharm Sci 2012; 101(2):616-26JP

Abstract

The aim of the present study was to evaluate and improve the in vitro transcorneal permeability characteristics of Δ(9) -tetrahydrocannabinol (THC) through prodrug derivatization and formulation approaches. In vitro corneal permeability of THC and its hemisuccinate (THC-HS) and hemiglutarate (THC-HG) ester prodrugs and WIN 55-212-2 (WIN), a synthetic cannabinoid, was determined using isolated rabbit cornea. The formulations studied included hydroxypropyl beta cyclodextrin (HPβCD) or randomly methylated beta cyclodextrin (RMβCD), as well as prodrug-ion-pair complexes with l-arginine or tromethamine. Corneal permeability of WIN was found to be two-fold higher than THC in the presence of HPβCD. THC-HS and THC-HG exhibited pH-dependent permeability. In the presence of HPβCD, at pH 5 (donor solution pH), both prodrugs exhibited six-fold higher permeability compared with THC. However, permeability of the prodrugs was about three-fold lower than that of THC at pH 7.4. RMβCD, at pH 7.4, led to a significant improvement in permeability. Formation of ion-pair complexes markedly improved the solubility and permeability of THC-HG (sevenfold and threefold greater permeability compared with THC and WIN, respectively) at pH 7.4. The in vitro results demonstrate that the use of an ion-pair complex of THC-HG could be an effective strategy for topical delivery of THC.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21989812

Citation

Hingorani, Tushar, et al. "Effect of Ion Pairing On in Vitro Transcorneal Permeability of a Δ(9) -tetrahydrocannabinol Prodrug: Potential in Glaucoma Therapy." Journal of Pharmaceutical Sciences, vol. 101, no. 2, 2012, pp. 616-26.
Hingorani T, Gul W, Elsohly M, et al. Effect of ion pairing on in vitro transcorneal permeability of a Δ(9) -tetrahydrocannabinol prodrug: potential in glaucoma therapy. J Pharm Sci. 2012;101(2):616-26.
Hingorani, T., Gul, W., Elsohly, M., Repka, M. A., & Majumdar, S. (2012). Effect of ion pairing on in vitro transcorneal permeability of a Δ(9) -tetrahydrocannabinol prodrug: potential in glaucoma therapy. Journal of Pharmaceutical Sciences, 101(2), pp. 616-26. doi:10.1002/jps.22791.
Hingorani T, et al. Effect of Ion Pairing On in Vitro Transcorneal Permeability of a Δ(9) -tetrahydrocannabinol Prodrug: Potential in Glaucoma Therapy. J Pharm Sci. 2012;101(2):616-26. PubMed PMID: 21989812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of ion pairing on in vitro transcorneal permeability of a Δ(9) -tetrahydrocannabinol prodrug: potential in glaucoma therapy. AU - Hingorani,Tushar, AU - Gul,Waseem, AU - Elsohly,Mahmoud, AU - Repka,Michael A, AU - Majumdar,Soumyajit, Y1 - 2011/10/11/ PY - 2011/02/21/received PY - 2011/08/10/revised PY - 2011/09/27/accepted PY - 2011/10/13/entrez PY - 2011/10/13/pubmed PY - 2012/5/12/medline SP - 616 EP - 26 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 101 IS - 2 N2 - The aim of the present study was to evaluate and improve the in vitro transcorneal permeability characteristics of Δ(9) -tetrahydrocannabinol (THC) through prodrug derivatization and formulation approaches. In vitro corneal permeability of THC and its hemisuccinate (THC-HS) and hemiglutarate (THC-HG) ester prodrugs and WIN 55-212-2 (WIN), a synthetic cannabinoid, was determined using isolated rabbit cornea. The formulations studied included hydroxypropyl beta cyclodextrin (HPβCD) or randomly methylated beta cyclodextrin (RMβCD), as well as prodrug-ion-pair complexes with l-arginine or tromethamine. Corneal permeability of WIN was found to be two-fold higher than THC in the presence of HPβCD. THC-HS and THC-HG exhibited pH-dependent permeability. In the presence of HPβCD, at pH 5 (donor solution pH), both prodrugs exhibited six-fold higher permeability compared with THC. However, permeability of the prodrugs was about three-fold lower than that of THC at pH 7.4. RMβCD, at pH 7.4, led to a significant improvement in permeability. Formation of ion-pair complexes markedly improved the solubility and permeability of THC-HG (sevenfold and threefold greater permeability compared with THC and WIN, respectively) at pH 7.4. The in vitro results demonstrate that the use of an ion-pair complex of THC-HG could be an effective strategy for topical delivery of THC. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/21989812/abstract/Effect_of_ion_pairing_on_in_vi L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)31719-6 DB - PRIME DP - Unbound Medicine ER -