Curt’s Cannabis Corner: What is Nanoemulsion Technology? Part 2

Welcome to the third installment in the series of educational articles from technical writer Curt Robbins at Higher Learning LV and MJBA’s MJNews Network. This collection is intended for cannabis and hemp industry professionals who wish to gain a better understanding of the nuanced biochemistry of this specialand newly legalherb. 

For the past two weeks, Curt has been teaching readers about the hot new manufacturing process for cannabis- and hemp-infused products called nanoemulsion

What is nanoemulsion? How can it help patients and consumers while offering additional marketing opportunities for entrepreneurs? How does it compare to traditional formulation technologies? Read on to learn!


CURT’S

CANNABIS

CORNER 

What is Nanoemulsion Technology?

Part 2

By Curt Robbins

 

 

Read What is Nanoemulsion Technology?: Part 1. In Part 1, readers learn the definition of nanoemulsion and how it is being employed in the cannabis and hemp industries for the creation of consumer products that feature enhanced bioavailability (including greater potency and faster onset). This formulation tech also allows more accurate dosing, a large advantage to millions of patients and their caretakers. 

In Part 2, let’s dive deeper into this excerpt from the Higher Learning LV course Cannabis Core Concepts by further exploring bioavailability issues, examining some real world metrics, and learning the latest scientific research about nanoemulsion technology! 

End Game: Increased Bioavailability

The purpose of packaging a medicine, wellness tonic, or lifestyle beverage in the form of a nanoemulsion is straightforward: To improve bioavailability. This includes not only greater potency, but also faster onset. 

Onset is an important issue for consumers who require quick relief from conditions such as chronic pain, nausea, seizure activity, and social anxiety, to name only a few. Most within this population cannot tolerate the approximately two-hour wait that characterizes the onset of standard infused edible products (especially given that peak potency requires an additional one to three hours). 

The exact onset period of a particular nanoemulsion depends on several factors, including consumption avenue and the biophysical circumstances under which it is consumed by users. This includes their age, relative health, genetic makeup, medical history, and use of commingling drugs.  

Edible cannabis products formulated with nanoemulsions typically involve an onset period of roughly 10-30 minutes, with 15-20 minutes being a common claim among companies offering infused beverages and edibles featuring nanoencapsulated cannabinoids and terpenes.   

A 2014 study entitled “Enhancement of the Oral Bioavailability of Breviscapine by Nanoemulsion Drug Delivery System” that was published in the journal Drug Development and Industrial Pharmacy explored the ability of a “nanoscale drug delivery system to realize the improvement of its oral bioavailability.” 

Reported the study, “the relative bioavailability of [the nanoencapsulated drug] reached 250 percent.” The researchers concluded that the nanoemulsion enhanced the oral absorption of [the drug] due to “improved stability and permeation.”  

A 2017 study entitled “Nanoemulsion-based Delivery System for Enhanced Oral Bioavailability” that was published in the journal Drug Delivery investigated the relative bioavailability of various formulation approaches, including nanoemulsion. “Nanoemulsion of BBH showed a relative bioavailability of 440 percent compared with unencapsulated BBH.” The study’s authors also reported that the nanoencapsulated liquid remained stable following a six-month evaluation period.  

If performed properly and depending on the exact compounds involved, nanotechnology can result in faster onset and greater potency at lowerand significantly more accuratedoses. This approach offers not only more efficient treatment of conditions such as pain and seizures, but also the economy resulting from smaller volumes of a particular compound or drug that yield greater potency.

Detailed Definitions

Research has revealed that bioavailability of cannabinoids such as CBD and CBG may be increased from as low as six percent in traditional, non-nanoemusified preparations (revealed by this study) to as great as 90 percent with nanoemulsified products (demonstrated by another study). 

According to a 2010 study entitled “Nanoemulsion: A Pharmaceutical Review,” nanoemulsion-based products are “by far the most advanced nanoparticle systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting.” The study noted that nanoemulsion droplet sizes within a particular sample, when accomplished successfully, feature “narrow size distributions” (variance).  

“Nanoemulsions are the thermodynamically stable isotropic system in which two immiscible liquids (water and oil) are mixed to form a single phase by means of an appropriate surfactant [or emulsifying agent] or its mix with a droplet diameter in the range of 0.5-100 nm,” reported the study’s authors. The research concluded that “nanoemulsion shows great promise for the future of cosmetics, diagnostics, drug therapies, and biotechnologies.”

According to a 2014 study published in the journal 3 Biotech, a nanoemulsion is a “fine oil/water or water/oil dispersion” featuring a droplet size range of 20–600 nm. The study explained that three primary types of nanoemulsions exist: “(a) oil in water nanoemulsion in which oil is dispersed in water, (b) water in oil nanoemulsions in which water droplets are dispersed in oil, and (c) bi-continuous nanoemulsions.”

Nanoemulsion Research Studies

Although a relatively new technology, serious peer-reviewed research reports have begun to emerge regarding nanoemulsions. These study results consistently demonstrate significantly greater bioavailability, including shorter onset periods and enhanced peak potency. Nanoemulsion tech has shown this effect for a variety of cannabis-derived compounds, including CBD.

A 2016 study entitled “Nanoemulsions: Formation, Properties, and Applications” that was published in the journal Soft Matter noted a number of advantages to the use of nanoemulsion technology for delivery of drugs, including a small size that “leads to useful properties such as high surface area per unit volume, robust stability, [and] optically transparent appearance.” 

The research also noted the different forms of drug delivery in which nanoemulsion technology can improve bioavailability, which include “topical, ocular, intravenous, internasal, and oral delivery.” 

The study reported that most nanoemulsions are transparent in appearance because the droplet size employed “is significantly smaller than the wavelength of visible light.” However, the researchers noted that product and drug formulators “can easily tune the appearance of nanoemulsions to range from transparent to milky white” through the adjustment of droplet size. 

A 2017 study entitled “Biocompatible Nanoemulsions Based on Hemp Oil and Less Surfactants for Oral Delivery of Baicalein with Enhanced Bioavailability” that was published in the International Journal of Nanomedicine aimed to “probe the potential of nanoemulsions consisting of hemp oil in ameliorating [improving] the oral bioavailability of [the flavonoid] baicalein.” 

The study involved a particle size of 90 nm and an impressive bioavailability (what the study called an “entrapment efficiency”) of 99.31 percent. It reported that the flavonoid’s oral bioavailability was increased by “up to 524.7 percent and 242.1 percent relative to the suspensions and conventional emulsions, respectively.” 

The research determined that the safety profile of the flavonoid-based nanoemulsion revealed safe oral consumption. “Our findings suggest that such a novel…preparative process provides a promising alternative to current formulation technologies” and that nanoencapsulation is suitable for “oral delivery of drugs that feature…bioavailability issues.”

A 2017 study entitled “Nanoemulsion: A Novel Eon in Cancer Chemotherapy” that was published in the journal Mini Reviews in Medicinal Chemistry investigated the role of nanoemulsions in the effective treatment of cancer. 

The study’s authors observed that nanoemulsions offer a new approach to improving the sometimes poor bioavailability issues that have plagued traditional preparations and formulations for generations. Reported the study, “the research fraternity has acknowledged nanoemulsions as…capable of effectively addressing the low bioavailability…issues associated with conventional anticancerous chemotherapeutic dosage forms.”

A 2019 study entitled “Development of a Novel Nano­emulsion Formulation to Improve Intestinal Absorption of Cannabidiol” that was published in the journal Medical Cannabis and Cannabinoids observed the relatively poor bioavailability of CBD when ingested orally. “Cannabidiol (CBD) is highly lipophilic [fat loving] and its oral bioavailability is known to be very low in humans.” 

The study developed a novel nanoemulsion preparation of CBD involving a droplet size of approximately 35 nm “to improve the poor solubility and absorption of CBD.” The research reported that significant improvements in bioavailability were afforded by the nanoemulsification process. The period to achieve peak bioavailability (delay from time of consumption) was shortened by 330 percent and its potency was increased by 65 percent compared to a traditional non-nanoemulsified CBD oil. 

The study’s authors observed that their research was “the first to develop a CBD-based nanoemulsion formulation for testing,” which they observed to “extensively enhance the absorption of CBD and improve its bioavailability.”

A 2019 study entitled “Quercetin Loaded Nanoemulsion-based Gel for Rheumatoid Arthritis” that was published in the journal Biomedicine & Pharmacotherapy explored the advantages of a nanoemulsified topical application for the treatment of arthritis. 

The study found the nanoemulsified gel to feature improved bioavailability and “confirmed adequate rheological behavior with a good texture profile and improved drug permeation.” The report’s authors concluded that the nanoemulsified gel featuring the flavonoid quercetin “is an efficient topical treatment strategy for rheumatoid arthritis.” 

A 2019 study entitled “Emulsiogenesis and the Emergence of Nanoemulsions” that was published in the journal Matter investigated “the origin of the first natural emulsions and the evolution in production, classification, and nomenclature of extremely fine colloidal emulsions.”

The study reported that the first emulsions in nature appeared without the help of homo sapiens (and long before their appearance on the planet), about three to four billion years ago. It detailed how the emergence of waterborne microbes “produced organic hydrocarbon molecules, which were large enough in molar mass that collections of [them] formed liquid oil droplets surrounded by water.”

The researchers explained how the history of human-crafted emulsions dates back more than one hundred years. “Small-scale emulsions have been the subject of serious scientific investigations for more than a century, leading to very important milestones in condensed matter.”

The study emphasized how nanoemulsion tech remains in its infancy and that future developments will lead to novel and commercially enticing methods of encapsulating particular types of molecules for storage, distribution, and consumptionall while maintaining maximum bioavailability. 

“Regardless of the trends in nomenclature used for classifying emulsions, it is clear that emulsions having the smallest attainable droplet sizes, increasingly complex chemical compositions, and even multiple internal compartments represent a fertile area for basic research and important applications over many decades to come,” concluded the study’s authors. 

It’s a Wrap

Nanoemulsion technology offers patients and lifestyle consumersand the companies that serve thema way to encapsulate wellness molecules such as CBD, CBG, and THC that features improved stability and greater bioavailability than more traditional formulation techniques, including standard oils and liposomes. 

Heavily regulated industries such as hemp and cannabis benefit significantly from products that are formulated in a manner that leads to maximum shelf life and that can ensure sometimes lengthy storage periods. Greater bioavailability, in turn, offers both lifestyle consumers and multiple patient populations the advantage of rapid onset and enhanced potency. Medical professionals and caretakers are demonstrating an affinity for nanoemulsions based on not only enhanced bioavailability, but also more accurate dosing.   

Copyright © 2021 Higher Learning LV™. All Rights Reserved. 

Curt’s Cannabis Corner: What is Nanoemulsion Technology? Part 1

Welcome to the second installment in the new series of educational articles from technical writer Curt Robbins at Higher Learning LV and MJNews Network. This collection is intended for cannabis and hemp industry professionals who wish to gain a better understanding of the nuanced biochemistry of this specialand newly legalherb. 

For the next two weeks, Curt will teach readers about the hot new manufacturing process for cannabis- and hemp-infused products called nanoemulsion

What is nanoemulsion? How can it help patients and consumers while offering additional marketing opportunities for entrepreneurs? How does it compare to traditional formulation technologies? Read on to learn!

The following is an excerpt from the Higher Learning LV instructor-led course Cannabis Core Concepts


CURT’S

CANNABIS

CORNER 

What is Nanoemulsion Technology?

Part 1

By Curt Robbins

Those who work in the cannabis industry know that there’s plenty of hype regarding a relatively new molecular infusion technology called nanoemulsion (sometimes labeled miniemulsion, ultrafine emulsion, or submicron emulsion). 

Operating at the extreme microscopic size level that scientists call nanoscale, nanoemulsion offers a slew of advantages over traditional formulation technologies such as non-emulsified oils, macroemulsions, and microemulsions involving liposomes. Unfortunately, nanoemulsion tech has also resulted in significant marketing hyperbole and marketplace confusion.    

For engineering nerds, an interesting fact of nanoemulsion tech is that various underlying methods can be employed to create a nanoparticle emulsion liquid. All of these approaches, including ultrasonic generators, rotor devices, and high pressure homogenizers, are intended to result in a lifestyle beverage or liquid medicine that efficiently delivers wellness molecules, including cannabinoids and terpeneswithout degradation or other loss of potency during their path from processing and packaging to consumption and onset of effects. 

Another major reason companies are excited about nanoemulsions: Speed of onset. This molecular encapsulation approach results in significantly faster onset of bioavailability. In some cases, nanoencapsulation reduces the onset wait period from two or more hours (a traditional infused product) to about fifteen minutes (a roughly 800 percent improvement). 

It should be noted that nanoemulsion technology does not magically make hydrophobic fat-soluble molecules like cannabinoids and terpenes water soluble (as the marketing materials of some companies would lead one to believe). Rather, it is a method by which these fat-loving, water-fearing chemical compounds can be efficiently stored and transported on the way to their biophysical destinations (in the case of cannabis and hemp, microscopic CB1 and CB2 cellular receptors within the brain, central nervous system, and tissues of the immune system).  

Overview

Nanoemulsion technology is quickly gaining popularity with wellness professionals, consumers, and emerging hemp and cannabis brands. This approach to the consumption of some types of molecules that display poor water solubilityincluding the cannabinoids, terpenes, and flavonoids produced by cannabisis complex in detail, yet easily grasped in general theory. 

Many cannabis and hemp companies, especially those offering products intended to enhance health and wellness, are flocking to nanoemulsion tech for two primary reasons: Improved stability and faster onset of bioavailability (with the bonuses of significantly greater potency and more accurate dosing). The potential downside of nanoemulsions? Production cost (especially at smaller volumes).

Improved stability is important for heavily regulated industries like hemp and cannabis that involve supply chains featuring detailed distribution cycles and sometimes lengthy storage periods. Faster onset is critical for patient populations where conditions such as pain, nausea, social anxiety, or seizures demand the fastest possible onset of efficacy.

Nanoemulsion involves use of an agitative force (such as ultrasonic sound waves) to break up a solution containing two liquified substances (often an oil and an aqueous [water] element) that, under normal circumstances and in traditional preparations, would not form a homogeneous mixture. 

The compound of medicinal or therapeutic focus, such as a cannabinoid like cannabidiol (CBD) or delta-8 tetrahydrocannabinol (THC), is infused into an oil. Despite their differences, cannabinoids, flavonoids, and terpenes share one trait: They are fat soluble but not water soluble. Because of this important biochemical characteristic, these molecules must be infused into a lipid (fat) or oil for practical consumption by humans.

This marriage of oil and water, with the oil acting as a carrier for medicinal wellness compounds such as cannabinoids like CBD and THC, is accomplished with the assistance of a third element called an emulsifying agent (a common example of which is lecithin). This relatively technical concoction produces what scientists and product formulators dub a “single phase” mixture that is comprised of extremely small particles that fall within the nanoscale range (described below).

Understanding Nanoscale

Nanoscale (and the entire model for scientific measurement) is based upon the metric system, not the English scheme of inches and feet. A nanometer is one billionth of a meter (a meter being 3.3 feet). The root term nano is derived from ancient Greek, where it means “dwarf.” 

A micron, or micrometer, is the unit of measure directly above nano and is 1,000 nanometers (nm). To better gain a sense of the size of nanoscale, consider that a human hair is about 75 microns (75 μm), or 75,000 nanometers, in diameter. A sheet of standard notebook paper is just slightly thicker, at about 100,000 nanometers. 

According to the U.S. federal government’s National Nanotechnology Initiative:

  • A strand of human DNA  is 2.5 nanometers in diameter
  • An inch contains 25,400,000 nanometers
  • A gold atom is about one third of a nanometer in diameter

Infused beverages or tinctures containing broad-spectrum (involving molecular filtering) and full-spectrum (lacking filtering) nanoemulsions of hemp or individual cannabinoids (such as CBD or cannabigerol [CBG]) are defined as chemically and physically stable liquid-in-liquid dispersions featuring relatively minuscule droplet sizes of approximately 100 nm. 

Some strict sources define particle (droplet) sizes that exceed 100 nm to be outside of the nanoscale. However, technically speaking, 50-999 nm serves as an acceptable industry standard for nanoencapsulation particle size. A February 2021 market analysis defined nanoemulsions as “oil-in-water emulsions with mean size ranging from 50 to 1000 nm” that feature an average droplet size of “between 100 and 500 nm.”

Bioavailability & Delivery Dynamics

Nanoemulsions manifest as liquid solutions packaged as tinctures, infused beverages, eye drops, topicals (creams, lotions, balms, etc.), or transdermal patches. They are designed to circumvent the relatively lengthy process of digestion that is performed by the stomach and liverwith the overall goal of improving bioavailability compared to conventional “edibles.” 

Nanoencapsulated liquids also avoid the potential harms caused by inhalation of smoke and vapor. While research has revealed cannabis vapor to be considerably safer than the combustion involved in smoking the herb, chronic consumption via either method of inhalation may lead to lung damage and conditions such as bronchitis. Nanoencapsulated edibles and sublingual tinctures, while slower in onset than inhalation (the fastest consumption avenue at only 2.5 minutes), offer an improved safety profile that, in many use cases, justifies the slower onset.    

Methods of creating nanoemulsions include sonication (the application of ultrasonic sound) and high-pressure homogenization. Nanoemulsions produce significantly greater overall bioavailability (described in detail below), including faster onset and enhanced potency. This is true not only when nanoemulsions are eaten, but also when they are consumed sublingually (as with tinctures) or via transdermal patches. This fact gives this particular emulsion technology an unusually broad application range within the cannabis industry. 

A 2015 research study entitled “Nanoemulsion: An Advanced Mode of Drug Delivery System” reported that nanoemulsions “are manufactured for improving the delivery of active pharmaceutical ingredients” and that the process involves a “thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent.” 

The improved stability of nanoencapsulated formulations makes them of significant interest to wellness professionals because they can increase the precision of dosing. This is of importance for many conditions, including those whose treatment involves compounds that feature biphasic response curves or other peculiarities that can be exploited by a lack of dosing accuracy. 

Tune in next week for What is Nanoemulsion Technology?: Part 2 when we’ll dig into the hard research evidence behind the value of nanoemulsion tech for both companies and consumers and learn more about bioavailability. Don’t miss it!