Document Detail

Effects of RM-beta-CD on sublingual bioavailability of Delta9-tetrahydrocannabinol in rabbits.
MedLine Citation:
PMID:  15955678     Owner:  NLM     Status:  MEDLINE    
The purpose of the present study was to develop novel cyclodextrin-containing sublingual formulations of cannabinoids. Complexation of model cannabinoids, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), with randomly methylated beta-cyclodextrin (RM-beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD), were studied by the phase-solubility method. Due to better complexation efficiency, RM-beta-CD was selected for further studies. Solid THC/RM-beta-CD and CBD/RM-beta-CD complexes were prepared by freeze-drying. The dissolutions of both THC and CBD in the presence and absence of RM-beta-CD were determined. THC was selected for in vivo studies: the pharmacokinetics of THC after both sublingual and oral administrations of ethanolic THC and THC/RM-beta-CD complex solutions were studied in rabbits. The aqueous solubility of CBD and THC increased as a function of CD concentration, showing A(L)- and A(P)-type diagrams for HP-beta-CD and RM-beta-CD, respectively. Dissolution rates of THC/RM-beta-CD and CBD/RM-beta-CD complexes were significantly (p < 0.05) higher than those of plain THC and plain CBD, respectively. The absolute bioavailability (F) of THC decreased in the following order: sublingual THC/RM-beta-CD solution (F = 12.1+/-1.4%; mean+/-S.D.; n = 4) > oral THC/RM-beta-CD solution (F = 4.0+/-6.0%) > or = sublingual ethanolic THC solution (F = 3.8+/-2.8%) > oral ethanolic THC solution (F = 1.3+/-1.4%). These results demonstrate that RM-beta-CD increases both the aqueous solubility and dissolution rate of these cannabinoids, making the development of novel sublingual formulation possible. These results also suggest that the sublingual administration of a THC/RM-beta-CD complex substantially increases the bioavailability of THC in rabbits.
Janne Mannila; Tomi Järvinen; Kristiina Järvinen; Maarit Tarvainen; Pekka Jarho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  26     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-08     Completed Date:  2006-04-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  71-7     Citation Subset:  IM    
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland.
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MeSH Terms
Administration, Oral
Administration, Sublingual
Biological Availability
Cannabidiol / chemistry
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid
Gas Chromatography-Mass Spectrometry
Tetrahydrocannabinol / administration & dosage,  chemistry,  pharmacokinetics*
Time Factors
beta-Cyclodextrins / administration & dosage,  pharmacology*
Reg. No./Substance:
0/beta-Cyclodextrins; 13956-29-1/Cannabidiol; 1972-08-3/Tetrahydrocannabinol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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