In this interview, Mark Bumiller, Scientific Instruments Technology Manager at Entegris, talks about cannabis emulsions and how they are used in the preparation of cannabis-infused products.
Can you explain what a cannabis emulsion is?
An emulsion is a mix of two liquids that do not typically mix. You can also call them a two-phase colloid suspension where both phases are liquid. In a cannabis emulsion, the dispersed phase is cannabis oil, and the continuous phase is water.
Since oil and water do not naturally mix, the chemistry is typically altered by adding surfactants, and energy is added to reduce the droplet size. The chemistry is similar whether the cannabis oil is primarily CBD or THC. But one of the challenges is that the oil chemistry will vary with the source and the process used to extract the oil.
How are these emulsions formulated?
First, define the goal of the product. You usually want a stable emulsion – it does not phase-separate with time. For example, if you have a poor formulation and you do not get the droplet size small enough, the oil phase separates, and the oil will coalesce or cream up to the surface.
When that happens, a consumer drinking the very first part of a beverage might take the entire dose in the first sip, potentially resulting in a problematic experience if they only want to consume a portion of the dose.
There is a complex relationship between emulsion stability and dose uniformity. Making sure doses are stable and predictable is a crucial consideration because consumers need to know that the effect of the beverage is relatively predictable. Harmful or unexpected effects can damage a product’s reputation, negatively impacting its brand and consumer confidence.
You should also have a taste in mind. I personally do not really like the taste of cannabis oil, it is bitter, and I do not like anything that is too bitter. I do not even drink coffee for the same reason. So sugar and other flavors (often other emulsions) are typically added to build a taste profile.
Then there is the chemistry of formulating a stable cannabis emulsion. The biggest decision is what surfactants to use and the surfactant concentration. HLB (Hydrophile-Lipophile Balance) theory can point you in the right direction. But for me, this tells me where not to go more than where to go.
Getting to an HLB number of around nine is usually about right for cannabis emulsions. But a lot of the surfactant choice is from reading the available literature and then trial and error in the lab.
At the Emerald Conference, I presented data showing an experiment where I tried to make my own formulation using just a chemical supply catalog, which resulted in very mediocre products.
For example, I was able to get the droplet size down to around 200 nanometers using a series of commercially available chemicals (Span 80 and Tween 80), but when I used a proven surfactant (Part B from Stuff Corp), I immediately achieved excellent results with a mean droplet size between 25 and 35 nanometers.
The choice of oil is also important for these experiments, and I opted to use a CBD oil purchased from a commercial retailer in Huntington Beach rather than a sample from a scientific provider. I was able to acquire a Certificate of Analysis for the commercially available CBD oil, confirming it contained 37 mg of CBD per ml.
Several companies out there will sell you a proven solution – often at a price point that might be higher than desired, especially if you scale up to commercial quantities.
If you are taking the science seriously, you are also testing the droplet size and surface charge, or zeta potential, along the way as indicators of emulsion type and predicted stability. That is my specialty.
What is the significance of the amount of energy used in emulsion formulation?
When you produce oils or emulsions, you need to add energy to mix the sample and actually break the droplets down to the small sizes required. This energy can be added using a mixer, a homogenizer, a microfluidizer or ultrasound.
In my study, I used an ultrasonic probe from Hielscher, I recently visited a cannabis production plant that was using a homogenizer, and I have also used microfluidizers in the past.
Image Credit: Shutterstock / beton studio
Why is droplet size so important?
Most companies want to create a nanoemulsion, indicating a specific droplet size range that implies greater stability or shelf life for the product. That droplet size range is typically under 100 nm, although that is a loose number depending on the context.
Many products available are marketed as nanoemulsions, but there are issues in the industry regarding the fact that the definition of a nanoemulsion and the droplet size associated with this definition are not standardized, and these are measured with different types of instruments and methodologies.
Dynamic Light Scattering (DLS) is one of the most reliable technologies for measuring droplet sizes and confirming that an emulsion is a nanoemulsion. We can also follow the ISO 22412 standard for presenting DLS results to make sure the results are standardized and comparable. Ideally, we should be reporting the intensity mean in the polydispersity index when presenting results from dynamic light scattering.
You typically adjust the surfactant selection and concentration to achieve the desired size range after adding energy to the system. I personally do not see how companies can market a product as a nanoemulsion without having made the droplet size measurements.
The other important consideration is the effect of the beverage on the consumer. Hopefully, it is a very happy effect. The size range of the droplets will influence how quickly the effect is felt.
When I spoke at the Emerald Conference in early March this year, the speaker just before me showed how reduced droplet size as measured on a Nicomp DLS system increased the bioavailability of the cannabis concentration in the bloodstream.
By reducing the droplet size, the medicinal (or recreational) effect occurs much quicker. Think about waiting 15-20 minutes to feel the effect rather than over an hour.
What about droplet surface charge? Why is that important?
Adding surfactant to the emulsion will alter the surface charge, and that influences stability. When you introduce a charge to the droplet surface, they start to repel each other like magnets. If they cannot get close enough to touch, they are less likely to coalesce and phase separate. Droplet size and zeta potential go hand in hand during new product formulation.
The other consideration is the pH of the final product. pH will alter the zeta potential and possibly negate the stabilization influence. There is a lot of literature on making an ideal surfactant choice, but it is important to remember that because cannabis beverages are food products, the formulators are limited to food-grade surfactants.
For example, if you formulate a drink at neutral pH, around 7, and then pour the beverage into a glass of wine with a pH of 4, the emulsion could quickly destabilize and phase separate. This is the type of study that I intend to investigate further for next year’s Emerald Conference.
How was your talk at the Emerald Conference received? Did you learn anything there?
I think my talk was well-received, and many attendees learned about technical issues that were entirely new to them. I certainly learned a lot about how complex cannabis chemistry is and the challenges of making consistently high-quality products. I hope I convinced people that testing is not only required but a good thing. I think this industry needs to be concerned about customers having bad experiences due to inconsistent quality. Companies need to have only happy customers.
One of the most important things at a conference like the Emerald Conference is the way that many people working with cannabis chemistry and products also use those products. That makes a real difference to their work because they are approaching this field from the perspective of both consumers and producers.
How does Entegris fit into this picture?
We fit in as a supplier of the particle size analyzers used to measure the droplet size and as a technical resource to understand how to use the systems properly for this application.
We supply two technology platforms: dynamic light scattering (DLS) systems to measure the mean size and zeta potential and single particle optical sizing (SPOS) to measure the tail of large droplets. Both play a role in helping to create high-quality beverages. We work with both the pharmaceutical and beverage industries to design and manufacture emulsions.
Entegris is also a company that is very willing to work with all legitimate cannabis companies, which is not always the case, I am told.
Does your experience from other industries directly apply to the cannabis industry?
To put it simply, yes. The large cola-type beverage companies have been using our AccuSizer SPOS system to study emulsions for years, and lipid emulsions injected into patients are tested using both the Nicomp DLS system and the AccuSizer to test both mean size and large droplet tail. The same principles apply to the cannabis beverage industry.
The United States Pharmacopeia (USP) writes quality tests for pharmaceutical products. Guidance in USP 729 PFAT5 requires that you measure the mean size of the emulsion using dynamic light scattering or laser diffraction and that the mean size must be under 0.5 microns or 500 nanometers.
The guidance also discusses a different technique based on single-particle optical sizing. Our AccuSizer range is able to measure, for example, how many droplets in the emulsion are greater than five microns, providing a very good indicator of emulsion stability.
How can manufacturers apply these technologies to gain market share?
I think the cannabis industry is now really starting to sort out the technologies required to formulate and manufacture consistent products. Plus, it is growing so fast that leading companies need to stay nimble to quickly bring new products onto the market as demand continues to grow
Doing this well requires a fundamental understanding of the chemistry, science and technology involved in medicinal and consumer beverages. The majority of cannabis beverage products are emulsions, and droplet size and surface charge are critical issues for these products. Personally, I do not see how a company could formulate and bring quality beverage products to market without understanding droplet sizing science.
Besides emulsions, are you seeing any other types of delivery products for CBD entering the market? How do these products impact measurement approaches?
Some of the beverage products currently available on the market are also liposomal, meaning that the product is based on liposomes. This lets the producers get the oil into water, not with an emulsion, but by hiding it in the bilayers of a liposome.
Particle size is equally critical when you create beverages with liposomes – particularly in terms of product stability - and dynamic light scattering is also the most typical technique used to determine the size of these liposomes.
About Mark Bumiller
Mark has worked in the field of particle size analysis for over 35 years. Positions held include product manager at Hiac Royco, technical support manager and vice president of business development at Malvern Instruments, vice president of particle products at Horiba and technology manager at Particle Sizing Systems, LLC, and now Entegris. He has served as a member of the expert committee for USP <788>, the executive committee of the International Fine Particle Research Institute (IFPRI), and the executive committee of Particle Technology Forum of the American Institute of Chemical Engineers. Mark is an active member of Technical Committee 24 within ISO helping to write standards for particle size and zeta potential analysis. His B.S. in chemical engineering was earned at Carnegie Mellon University in Pittsburgh, PA.
This information has been sourced, reviewed and adapted from materials provided by Entegris.
For more information on this source, please visit Entegris.
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