Solid dispersions based on inulin for the stabilisation and formulation of delta 9-tetrahydrocannabinol

D J van Drooge*, W L J Hinrichs, K A M Wegman, M R Visser, A C Eissens, H W Frijlink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Scopus)

Abstract

The aim of this study was to develop a dry powder formulation that stabilises the chemically labile lipophilic Delta(9)-tetrahydrocannabinol (THC), that rapidly dissolves in water in order to increase the bioavailability and that opens new routes of administration. It was investigated whether these aims can be achieved with solid dispersions consisting of a matrix of inulin, an oligo-fructose, in which THC is incorporated. These solid dispersions were prepared by lyophilisation of a solution of THC and inulin in a mixture of water and tertiary butyl alcohol (TBA). Both 4 and 8 wt.% of THC could be incorporated in a glassy matrix of inulin. In the solid dispersions only 0.4-0.5 wt.% of residual TBA was present after storage at 20 degreesC/45% relative humidity (RH) for 7 days. Unprotected THC was completely degraded after 40 days of exposure to 20degreesC and 45%RH. However, solid dispersions exposed to the same conditions still contained about 80% non-degraded THC after 300 days. Dissolution experiments with tablets compressed from inulin glass dispersion material showed that THC and inulin dissolved at the same rate. Tablets weighing 125 mg and containing 2 mg THC were prepared from a mixture of THC containing solid dispersion, polyvinylpolypyrrolidone (PVPP) and mannitol. Dissolution tests revealed that from these tablets 80% of the THC was dissolved within 3 min, which makes them promising for sublingual administration. It was concluded that THC can be strongly stabilized by incorporating it in a matrix of inulin. The aqueous dissolution rate was high which may improve bioavailability. (C) 2004 Elsevier B.V All rights reserved.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume21
Issue number4
DOIs
Publication statusPublished - 1-Mar-2004

Keywords

  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Dronabinol
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Inulin
  • Tablets

Cite this