title: Spray freeze drying to produce a stable Delta(9)-tetrahydrocannabinol containing inulin-based solid dispersion powder suitable for inhalation.
abstract: The purpose of this study is to investigate whether spray freeze drying produces an inhalable solid dispersion powder in which Delta(9)-tetrahydrocannabinol (THC) is stabilised. Solutions of THC and inulin in a mixture of tertiary butanol (TBA) and water were spray freeze dried. Drug loads varied from 4 to 30 wt.%. Various powder characteristics of the materials were determined. Stability of THC was determined and compared with freeze dried material. The powders, dispersed with an inhaler based on air classifier technology, were subjected to laser diffraction analysis and cascade impactor analysis. Highly porous particles having large specific surface areas (about 90 m(2)/g) were produced. At high drug loads, THC was more effectively stabilised by spray freeze drying than by freeze drying. Higher cooling rates during spray freeze drying result in improved incorporation. Fine particle fractions of up to 50% were generated indicating suitability for inhalation. It was concluded that spray freeze drying from a water-TBA mixture is a suitable process to include lipophilic drugs (THC) in inulin glass matrices. High cooling rates during the freezing process result in effective stabilisation of THC. The powders can be dispersed into aerosols with a particle size appropriate for inhalation.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands. d.j.van.drooge@rug.nl
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: van Drooge
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
authors.forename: Bastiaan H J
authors.initials: BH
authors.lastname: Dickhoff
authors.forename: Marco N A
authors.initials: MN
authors.lastname: Elli
authors.forename: Marinella R
authors.initials: MR
authors.lastname: Visser
authors.forename: Gerrit S
authors.initials: GS
authors.lastname: Zijlstra
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D013759:Dronabinol / Q000737:chemistry*; D004355:Drug Stability; D005612:Freeze Drying; D007444:Inulin; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry; D020002:tert-Butyl Alcohol / Q000737:chemistry
chemical_list: D000336:Aerosols; D011208:Powders; D014867:Water; D013759:Dronabinol; D007444:Inulin; D020002:tert-Butyl Alcohol