Rational design, synthesis, and characterization of a solid Δ9-tetrahydrocannabinol (THC) nanoformulation suitable for “microdosing” applications

Background: This paper highlights the formulation of a solid THC-loaded ingestible prepared from pure THC distillate. A THC ethanol-assisted cannabinoid nanoemulsion (EACNE) was created without the need for specialized emulsification equipment such as a high-pressure homogenizer or a microfluidizer. Stress-testing was performed on the EACNE to evaluate its chemical and colloidal stability under the influence of different environmental factors, encompassing both physical and chemical stressors. Subsequently, the EACNE was converted to a solid powdery material while still retaining its THC potency, and suited for “microdosing” applications. Methods: An ethanol-assisted emulsification method was used to generate a THC nanoemulsion. The EACNE was fully characterized, imaged, and subjected to stress-tests. The EACNE was then mixed with a solid matrix material post facto and lyophilized to create a solid ingestible substance. Upon ball-milling, a dense powdery material was obtained. Flow properties and thermal properties of this material were recorded. Potency of the material was evaluated in triplicate using HPLC and correlated with the potency of the starting EACNE. Results: EACNE had an average lipid droplet size of ca. 190 nm, with a polydispersity index (PDI) of 0.15, and an average droplet zeta potential of -49±10 mV. The nanoemulsion was colloidally stable for at least 6 weeks, with no meaningful change in cannabinoid potency over the experimental period, as determined by HPLC analysis. The EACNE remained stable when subjected to physical stresses such as heat, freeze/thaw cycles, carbonation, dilution to beverage concentrations, high sucrose concentrations, and a pH range between 5-8. The effect of undesirable events during the lyophilization of the EACNE were minimized by ball-milling the resulting solid. The microencapsulated EACNE demonstrated limited free-flowing behaviour but was freely redispersible in water without any visible phase separation. Conclusions: A solvent-mediated emulsification protocol creates a THC-loaded nanoemulsion that can subsequently be converted to a water-soluble powder. These materials are particularly suited for THC “microdosing”, a practice that might decouple the health benefits of THC from its psychotropic effects.