Nano-Emulsification

Nano
Emulsion

We are the world’s most trusted expert on cannabis emulsions. Le Herbe pioneered this food science innovation in 2015 when we developed a proprietary emulsion technology to disperse nano-sized oil droplets in water. Le Herbe makes single-emulsions, double-emulsions, macroemulsions, nanoemulsions, or microemulsions for a wide variety of cannabis products, including drinks and edibles. We make emulsions with delta-8 THC (D8), delta-9 THC (D9), THCa, THCv, and much more. The information below is designed to help small businesses and artisan makers. You can try to make an emulsion with THC yourself or hire a professional; the choice is yours.

How to make a cannabis emulsion

Equipment

High-Pressure
Sonication
Rotor-Stator
Combination

Types

Oil-in-Water (o/w)
Water-in-Oil (w/o)
Double-Emulsion (w/o/w or o/w/o)

Process

Continuous Process
Batch Process

Carrier Oil

Medium-Chain Triglycerides (MCT)
Long-Chain Triglycerides (LCT)

Essential Oils

Orange Oil
Lemon Oil
Lime Oil
Peppermint Oil
Clove Oil
Cinnamon Oil
Thyme Oil

*Full Spectrum

Terpenes

d-Limonene
Linalool
α-Pinene
β-Pinene
β-Myrcene
α-Caryophyllene
β-Caryophyllene

*Isolated

Optics

Transparent - Clear (< 40nm)
Translucent - Hazy (40-100nm)
Opaque - White (> 100nm)

*nm = nanometers

Quality Attributes

Particle Size (< 100nm)
Monodisperse (< 0.2 PDI)
Zeta Potential (± 30 mV)
Encapsulation Efficiency (+ 90% EE)

Benefits

Enhance bioavailability (+75%)
Decrease onset times (fast-acting)
Protect cannabinoids from degradation
Modify the taste properties (flavorless)
Modify the smell properties (odorless)
Modify the optical properties (transparent)
Increase shelf-stability and long-term storage

Additional Info

Size matters in drug delivery, and a nanoemulsion is the most versatile delivery system the world has ever seen.

Various processing methods are available for the production of THC nanoemulsions (< 100nm), which can be divided into high- and low-energy methods. High-energy methods employ specially designed homogenizers that subject oil and water phases to intense disruptive forces to create nano-sized oil droplets. This includes high-pressure, sonication, and rotor-stator.

The particle size distribution, mean particle diameter, and polydispersity index (PDI) play a key role in determining the functional attributes of cannabis nanoemulsions. Careful selection of the emulsifier is critical to any formulation. Le Herbe recommends using all-natural emulsifiers like phospholipids. Oil-in-water emulsions are often used as templates to form other types of structures, like amorphous solid dispersions (ASD). These non-crystalline particles encapsulate nanoemulsions via spray drying and are converted into microparticles. Cannabis powder is a collection of microparticles and can be used dry or re-dispersed in water. Le Herbe THC emulsions are the gold standard for food and beverage formulations, including cannabis drinks, artisanal chocolate, fresh baked goods, edibles, and much more.

Experiment

A brief overview of this experiment will focus on making cannabis emulsions via sonication so that others may start or find useful such information. Initially, response surface methodology (RSM) was performed to optimize the formulation variables of oil-in-water (o/w) emulsions induced by ultrasound. The optimal formulation variables, as predicted by RSM, resulted in improved physical characteristics of emulsions formulated with cannabis by minimizing their droplet size, polydispersity index, and viscosity. Moreover, the cannabis nanoemulsions exhibit excellent stability over a long period of time (1 year), under different storage conditions (cold or hot), and in a wide range of environments (pH).

Methods & Materials

Cannabis sativa L. and olive oil were chosen as the dispersed phase (oil) for an oil-in-water (o/w) emulsion. The cannabis oil was produced via ultrasound-assisted extraction (UAE) from fresh frozen cannabis inflorescences (Le Herbe). The olive oil has been produced via traditional cold press (Berkeley Olive Grove). For reducing the interfacial tension between oil and water, two types of emulsifying agents have been selected based on previous data and their HLB value. Tween 80 (HLB = 15) and Span 80 (HLB = 4.3) (Sigma-Aldrich Co.) were used as emulsifying agents because of their Generally Recognized As Safe (GRAS) status. Q700 (Qsonica) was used for generating the ultrasound with a maximum power input of 700 W and a frequency of 20 kHz. These experiments were conducted in batches using a 500 ml jacketed reaction beaker (Kimble Chase) connected to a compact recirculating chiller (Qsonica) operating at a temperature of less than 25 °C. After ultrasonication, the mean particle diameter was measured using dynamic light scattering (DLS) by a Zetasizer Nano (Malvern). Deionized water was used for the preparation of all formulations (Thermo Fisher). The pH of the suspensions was measured with a micro-pH 2000 (Crison)

Preparation

Emulsions were formulated using oil, surfactants, water, and sonication. The dispersed phase (cannabis/olive oil containing Span 80) was heated to 110 °C and allowed to cool (24 hrs) in a nitrogen atmosphere for complete dissolution of the surfactant, decarboxylation of cannabinoids, and protection from degradation. The continuous phase (water containing Tween 80) was also heated up to 45 °C and allowed to cool (24 hrs) for complete dissolution. The emulsification was carried out using a two-step homogenization process. The first step is to produce a coarse o/w emulsion. The dispersed phase was added drop-by-drop to the continuous phase using a magnetic stirrer (500 rpm for 5 min) at ambient temperature (25 °C). The second step is to immediately take the coarse emulsion and apply ultrasonication. The high-frequency voltage output of the generator (Q700) was converted into mechanical vibrations by piezoelectric transducers into a standard horn with a tip diameter of 1/2" (12.7 mm), placed at the center of the beaker, and a depth of 3 cm. The amount of amplitude (as a percentage of the maximum amplitude, 120 μm) was kept constant by the control electronics of the generator. Ultrasonic exposure was applied in a continuous process. The same experiment was repeated with varying sonication times (min), surfactant fractions, oil fractions, high-power amplitude, and different hydrophilic lipophilic balance (HLB) values.

Results & Discussions

Hydrophilic Lipophilic Balance (HLB)

In the first published set of experiments, hydrophilic lipophilic balance (HLB) concept shows the amphiphilicity for non-ionic surfactants. The desired HLB was obtained by mixing Tween 80 and Span 80 at desired ratios. The prepared samples were diluted and then analyzed to determine particle size distribution in nanometers (nm). FIG 1 shows, except HLB 9, an increase in HLB led to a decrease in particle size and optical density, but beyond HLB 13 the droplet size remained constant. Surfactant(s) with low HLB less than 7 gives water-in-oil w/o emulsions whereas high HLB more than 7 gives oil-in-water emulsions (o/w). Generally, mixed-surfactant systems are more effective than a single-type surfactant in retarding the particle aggregation. Simultaneous application of lipophilic and hydrophilic surfactants facilitate the formation of small particles using high-power ultrasonication. After optimization of HLB value, the effect of surfactant volume fractions in the range of 0.02 to 0.14 was investigated.

Variation of Surfactant & Oil Fraction on MDS

In the next set of experiments, surfactant(s) are required to decrease the interfacial tension and hence the shear forces required to break up the droplets into smaller droplets. The optimum surfactant volume fraction was found at 0.08, which was highly stable with the least amount of surfactants. The oil fraction was held constant from previous data at 0.10, which was found to be optimum as the emulsion exhibited lower droplet size and high stability after 5 minutes. As the surfactant concentration increases, the appearance of emulsion becomes translucent from white color, which indicates the formation of nano-emulsion at high-power amplitude. After optimization of surfactant volume fraction, the effect of sonication time 1, 2, 3, 4, 5, 6, 7, 8 min was investigated.

Effect of Sonication Time

In the final published set of experiments, emulsions were prepared by varying sonication times at high-power amplitudes of 60% - 70%. The optimum HLB value of 12, oil fraction of 0.10 and surfactant fraction 0.08 were chosen from FIG 1 & 2. There was a significant decrease in the MDS with an increase in sonication time from 1 to 5 min. Sonication time of 7.5 min was found optimum as further increase in time had little effect on the MDS reduction. Careful control of the temperature should be carried out during ultrasonication. After 5 min of sonication, the emulsion appeared translucent and very stable. 5 minutes via a continuous process may be selected in order to avoid overheating, which can degrade sensitive bioactive compounds such as cannabinoids, terpenoids and flavonoids.

Scale

Lab or bench scale units are necessary to reduce costs and risks while identifying optimal parameters before scaling up with ultrasonic cannabis technology. Flow-through cells that incorporate multiple horns are effective at providing uniform delivery of ultrasound to large volumes of material.

Conclusion

The present overview and experiment briefly reports on cannabis emulsions stabilized by Span 80 and Tween 80 at different operating conditions. Effects of various operating parameters such as HLB value, surfactant fraction, oil fraction, sonication times and high-power amplitude were investigated and optimized on the basis of droplet size and stability of emulsions. The ability of ultrasound to produce unique, high-value products with improved functionality, while reducing chemical and energy consumption in cannabis emulsions is revolutionary. It is envisioned that the continual development of this technology will lead to gradual industrial uptake of ultrasonics and eventually mainstream adoption for the production of valuable consumer packaged goods (CPG) like cannabis beverages and THC powder.

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