“Nano” has become one of the newest buzzwords on cannabis packaging, but consumers and businesses are confused about what the word really means. As a cannabis scientist, I make a lot of products for many different ingestion methods. In particular, I am developing many foods that use water-soluble emulsions and Nanoemulsions. Let me tell you a little bit about them and how they really work.
As you have probably learned, the effects of cannabinoids can vary greatly depending on the method of administration. Smoking and vaporizing lead to effects very quickly. Oral administration, for example via beverages, tinctures and food, is a completely different story, however. The pharmacology of food (e.g. drug use, effects and mechanisms of action) can be complex depending on the type and concentration of cannabinoids and the food matrix.
For a common edible product containing oil-soluble cannabinoids, absorption occurs as follows. In the stomach, an enzyme (gastric lipase) begins to break down the cannabinoid (fat) and chops the fat into small droplets. Then another lipase from the pancreas attaches to these droplets. Finally, bile salts from the gallbladder make the droplets water soluble to help digestion. In simpler language, cannabinoids need to be converted into an emulsion before they can be absorbed. However, the entire process is associated with low bioavailability, delayed onset of action and poor reproducibility.
To overcome these obstacles, cannabinoids can be incorporated into oil-in-water emulsions or nanoemulsions before ingestion. This improves the release of oil-soluble (lipophilic) bioactive substances by behaving like water-soluble (hydrophilic) compounds. It should be noted that only a few companies specifically design the composition and structure of their products in such a way that bioavailability is controlled. Unfortunately, this means that when you work with these companies, you leave a lot of bioavailability on the table.
Perhaps you’ve heard of nanotechnology and imagined something like little robots doing wonderful things. In reality, “nano” is a prefix that means “one billionth”. It is used with the metric system as a substitute for nanometers (nm), which is only a billionth part of a meter. As mentioned earlier, fats need to be emulsified in order to be digested. However, the ability of bioactive fats to interact with cell membranes in the stomach is also improved when the droplet size is decreased, thereby increasing their biological activity. This means that an emulsion is a great way to increase the bioavailability of cannabinoids, but a nanoemulsion where the droplets are 100 nm or smaller is even better.
Nanoemulsions can be defined as oil-in-water emulsions with droplet diameters in the range from 50 nm to 1000 nm. Typically, the average droplet size is between 100 nm and 200 nm. Nanoemulsions are by far the most advanced nanoparticle system for the systemic delivery of biologically active agents for the controlled delivery and targeting of drugs. They increase the water dispersibility of bioactive substances, protect bioactive substances from chemical degradation, increase their bioavailability and aim at the release of bioactive substances in the gastrointestinal tract.
Like emulsions, nanoemulsions contain emulsifiers, oil-soluble molecules (e.g. cannabinoids), medium-chain triglyceride oil (MCT) and water-soluble molecules (e.g. water and sugar). However, in order to develop a stable and efficient emulsion, physical-chemical properties such as viscosity, density, refractive index and interfacial tension as well as the stability of the nanodroplets must be taken into account. So they are not easy to make.
To make an emulsion, the hydrophobic (oil-soluble) cannabinoids must be entrapped in some form of “colloidal” particles before they can be dispersed in water. These colloidal particles typically have an oil-soluble center in which the cannabinoids are dissolved and a water-soluble shell that is in contact with the water. This enables the formation of droplets that are suspended in a liquid. Examples of emulsions are milk, mayonnaise and pralines.
Nanoemulsions have several advantages over emulsions:
- Nanoemulsions can have droplets whose diameter falls below 100 nm. They are therefore transparent and can easily be passed through a sterile filter (220 nm pore size) to remove microbial or particulate contamination.
- Nanoemulsions have a much larger surface area and free energy than emulsions, which makes them an effective transport system.
- Nanoemulsions do not exhibit the creaming, flocculation, coalescence and sedimentation problems that are common with emulsions.
- Nanoemulsions can be formulated in a variety of compounds such as foams, creams, liquids, and sprays.
- Nanoemulsions are made with GRAS ingredients (generally recognized as safe) that are approved by the U.S. Food and Drug Administration. They are non-toxic and non-irritating, so they can be easily applied to the skin and mucous membranes. In addition, they do not damage healthy human or animal cells and are therefore suitable for therapeutic use in humans and in the veterinary field.
The main components in the manufacture of nanoemulsions are:
- Oil (to solubilize the lipophilic molecules / active ingredients).
- Surfactant (emulsifier).
- Co-surfactant (enhances the effect of the surfactant).
The production of a nanoemulsion requires a lot of energy. The process should not only produce nano-sized droplets, but also maintain the stability of the droplets. The processes used are high pressure homogenization, ultrasound, phase inversion and microfluidization (patented). Let’s briefly see the theory behind each of these procedures.
High pressure homogenizers: Due to the strong pressure, the interface between water and oil is deformed so much that the droplets formed break up into smaller ones. This method requires a lot of energy, either mechanically or chemically. A high pressure homogenizer is commonly used by milk processors to reduce the size of the fat globules and to make the milk solids even.
Ultrasonic: This is one of the best methods for making nanoemulsions on a small scale. it cannot be done on a large scale. In this method, sound creates waves that move the molecules quickly, causing the oil droplets to move and disperse around the liquid. In addition, the sound waves create a lot of turbulence, which helps the oil droplets break down into nanoparticles.
Phase inversion: This process uses energy generated by chemical reactions. Chemical energy is a result of phase transitions that take place through emulsification. Phase inversion is a very sophisticated process that changes the solubility of surfactants through various factors such as temperature and concentration.
Spontaneous emulsification: This is an energy saving process. The procedure is carried out at ambient temperature without special equipment. Simply add water to a solution of oil and surfactant and stir gently. The process depends on the phase transition area, the surfactant concentration, the surfactant structure, the interfacial and bulk viscosity and the interfacial tension. It has one major limitation: the oil concentration is lower than other methods.
Microfluidization: This method is more efficient than the methods discussed earlier, but it requires very specialized equipment called microfluidizers. The microfluidizer is a static high pressure mixer. It requires control of several parameters and many factors that affect the synthesis of the nanodroplets, including the type of chamber in the equipment, the number of reservoirs in the equipment (one or two), the rheological properties of the ingredients (how the ingredients deform or flow in response to applied forces or tensions), the type of emulsifier, re-coalescence of emulsion droplets (how quickly small droplets come together to form larger droplets), and the time and energy used during the process. The process is the most efficient, but also the most complicated, specialized, and expensive.
Nanoemulsions have some important advantages and disadvantages that are not available with other emulsions, but they can be difficult to find in a way that maximizes the benefits. To make matters worse, many emulsion suppliers can be a bit misleading about the pros and cons. Make sure your emulsion work is done by experts.
Carolina Vazquez Mitchell is the creator of the Luchador and Cannabis Sleep Aid Dream she formulated to treat her own insomnia while studying chemistry at the University of Southern California. She has developed more than fifty cannabis products, ran a cannabis testing laboratory, and was named one of DOPE Magazine’s Outstanding Women in Cannabis.