Formulation of Cannabidiol in Colloidal Lipid Carriers
In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C.
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or continue reading here: Francke, N.M.; Schneider, F.; Baumann, K.; Bunjes, H. Formulation of Cannabidiol in Colloidal Lipid Carriers. Molecules 2021, 26, 1469. https://doi.org/10.3390/molecules26051469
Materials
Cannabidiol was obtained from THC Pharm (Frankfurt, Germany). Tetrahydrofuran of high-performance liquid chromatography (HPLC) quality for UV spectroscopy was purchased from Sigma-Aldrich (Steinheim, Germany). Tetrahydrofuran of Ultra LC–MS grade and acetonitrile of LC–MS grade for HPLC measurements were ordered from Carl Roth (Karlsruhe, Germany), as well as sodium azide. Refined soybean oil and refined rapeseed oil were obtained from Caelo (Hilden, Germany). Lipofundin® MCT/LCT 10% (referred to as Lipofundin® in the following and composed of 5% soybean oil, 5% medium chain triglycerides, 2.5% glycerol, 0.8% egg lecithin and unspecified quantities of α-tocopherol and sodium oleate [18,19]) was obtained as commercial colloidal lipid emulsion from B.Braun (Melsungen, Germany). Poloxamer 188 (Kolliphor® P 188) and poloxamer 407 (Kolliphor® P 407) were kind gifts from BASF (Ludwigshafen, Germany) and trimyristin (Dynasan® 114) and medium chain triglycerides (Miglyol® 812 N) from IOI Oleo (Witten, Germany), respectively.
Conclusions
Colloidal lipid emulsions are a promising option for the formulation of CBD. The achievable CBD load was extraordinarily high for all investigated systems, whereby the absolute drug load depended on the lipid used and its physical state. Although the stability of the emulsions was limited under mechanical stress conditions, initial interventions demonstrated that there are ways to improve the stability.
Concerning the physicochemical properties of the lipid core, loading with CBD caused an increase in the density of the matrix which became less pronounced with increasing CBD concentration. In addition to its localization and interaction with the lipid matrix, CBD was partly localized at the interface of the emulsion droplets.
The strong supercooling tendency of CBD enabled the production of colloidal emulsions in which the dispersed phase only consisted of the drug. Despite the low stability of these emulsions of supercooled pure CBD, the results indicate a further interesting option in CBD formulation.