van Drooge Dirk-Jan, Hinrichs Wouter L J, Dickhoff Bastiaan H J, Elli Marco N A, Visser Marinella R, Zijlstra Gerrit S, Frijlink Henderik W
Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.
Eur J Pharm Sci. 2005 Oct;26(2):231-40. doi: 10.1016/j.ejps.2005.06.007.
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.
本研究的目的是调查喷雾冷冻干燥是否能产生一种可吸入的固体分散体粉末，其中Δ⁹-四氢大麻酚（THC）得以稳定。将THC和菊粉在叔丁醇（TBA）与水的混合物中的溶液进行喷雾冷冻干燥。药物负载量在4至30 wt.%之间变化。测定了材料的各种粉末特性。测定了THC的稳定性，并与冷冻干燥材料进行比较。基于空气分级器技术用吸入器分散的粉末进行了激光衍射分析和级联冲击器分析。制备出了具有大比表面积（约90 m²/g）的高度多孔颗粒。在高药物负载量下，喷雾冷冻干燥比冷冻干燥更有效地稳定了THC。喷雾冷冻干燥过程中较高的冷却速率导致包封率提高。产生了高达50%的细颗粒部分，表明适合吸入。得出的结论是，从水 - TBA混合物中进行喷雾冷冻干燥是将亲脂性药物（THC）纳入菊粉玻璃基质的合适工艺。冷冻过程中的高冷却速率导致THC有效稳定。这些粉末可以分散成适合吸入的粒径的气雾剂。
