Tag Archives: solvent

Pesticide Remediation by CPC

By Arpad Konczol, PhD
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Like any other natural product, the biomass of legal cannabis can be contaminated by several toxic agents such as heavy metals, organic solvents, microbes and pesticides, which significantly influence the safety of the end products.

Let’s just consider the toxicological effects. Since cannabis products are not only administered in edible forms but also smoked and inhaled, unlike most agricultural products, pesticide residue poses an unpredictable risk to consumers. One example is the potential role of myclobutanil in the vape crisis.

Unfortunately, federal and state laws are still conflicted on cannabis-related pesticides. Currently, only ten pesticide products have been registered specifically for hemp by the U.S. Environmental Protection Agency. So, the question arises what has to be done with all pf the high-value, but also contaminated cannabis, keeping in mind that during the extraction processes, not only the phytocannabinoids get concentrated but the pesticides as well, reaching concentrations up to tens or hundreds of parts per million!

Currently, there are three different sets of rules in place in the regulatory areas of Oregon, California and Canada. These regulations detail which pesticides need to be monitored and remediated if a certain limit for each is reached. Because the most extensive and strict regulations are found in Canada, RotaChrom used its regulations as reference in their case study.

Centrifugal Partition Chromatographic (CPC) system

To illustrate that reality sometimes goes beyond our imagination, we evaluated the testing results of a THC distillate sample of one of our clients. This sample contained 9 (!) pesticides, of which six levels exceeded the corresponding action limits. The most frightening, however, regarding this sample, is that it contained a huge amount of carbofuran, a category I substance. It is better not to think of the potential toxicological hazard of this material…

The CPC-based purification of CBD is a well-known and straightforward methodology. As the elution profile on the CPC chromatogram of a distillate shows, major and minor cannabinoids can be easily separated from CBD. At RotaChrom, this method has been implemented at industrial-scale in a cost effective and high throughput fashion. In any case, the question arises: where are the pesticides on this chromatogram? To answer this, we set ourselves the goal to fully characterize the pesticide removing capability of our methodologies.

Our results on this topic received an award at the prestigious PREP Conference in 2019. The ease of pesticides removal depends on the desired Compound of Interest.

Here is a quick recap on key functionalities of the partition chromatography.

  • Separation occurs between two immiscible liquid phases.
  • The stationary phase is immobilized inside the rotor by a strong centrifugal force.
  • The mobile phase containing the sample to be purified is fed under pressure into the rotor and pumped through the stationary phase in the form of tiny droplets (percolation).
  • The chromatographic column in CPC is the rotor: cells interconnected in a series of ducts attached to a large rotor
  • Simple mechanism: difference in partition

Let’s get into the chemistry a bit:

The partition coefficient is the ratio of concentrations of a compound in a mixture of two immiscible solvents at equilibrium. This ratio is therefore a comparison of the solubilities of the solute in these two liquid phases.

The CPC chromatogram demonstrates the separation of Compounds of Interest based on their unique partition coefficients achieved through a centrifugal partition chromatography system.

CPC can be effectively used for pesticide removal. About 78% of the pesticides around CBD are very easy to remove, which you can see here:

In this illustration, pesticides are in ascending order of Kd from left to right. CBD, marked with blue, elutes in the middle of the chromatogram. The chart illustrates that most polar and most apolar pesticides were easily removed beside CBD. However, some compounds were in coelution with CBD (denoted as “problematic”), and some compounds showed irregular Kd-retention behavior (denoted as “outliers”).

If pesticides need to be removed as part of THC purification, then the pesticides that were problematic around CBD would be easier to remove and some of the easy ones would become problematic.

To simulate real-world production scenarios, an overloading study with CBD was performed, which you can see in the graph:

It is easy to see on the chromatogram that due to the increased concentration injected onto the rotor, the peak of CBD became fronting and the apparent retention shifted to the right. This means that pesticides with higher retention than CBD are more prone to coelution if extreme loading is applied.

To be able to eliminate problematic pesticides without changing the components of the solvent system, which is a typical industrial scenario, the so-called “sweet spot approach” was tested. The general rule of thumb for this approach is that the highest resolution of a given CPC system can be exploited if the Kd value of the target compounds fall in the range of 0.5-2.0. In our case, to get appropriate Kd values for problematic pesticides, the volume ratio of methanol and water was fine-tuned. Ascending mode was used instead of descending mode. For the polar subset of problematic pesticides, this simple modification resulted in an elution profile with significantly improved resolution, however, some coelution still remained.

In the case of apolar pesticides, the less polar solvent system with decreased water content in ascending mode provided satisfactory separation.

Moreover, if we focus on this subset in the three relevant regulatory areas, the outcome is even more favorable. For example, myclobutanil and bifenazate, dominant in all of the three regulatory regions, are fully removable in only one run of the CPC platform.

Based on these results, a generic strategy was created. The workflow starts with a reliable and precise pesticide contamination profile of the cannabis sample, then, if it does not appear to indicate problematic impurity, the material can be purified by the baseline method. However, if coeluting pesticides are present in the input sample, there are two options. First, adjusting the fraction collection of the critical pesticide can be eliminated, however the yield will be compromised in this case. Alternatively, by fine-tuning the solvent system, a second or even a third run of the CPC can solve the problem ultimately. Let me add here, that a third approach, i.e., switching to another solvent system to gain selectivity for problematic pesticides is also feasible in some cases.

In review, RotaChrom has conducted extensive research to analyze the list of pesticides according to the most stringent Canadian requirements. We have found that pesticides can be separated from CBD by utilizing our CPC platform. Most of these pesticides are relatively easy to remove, but RotaChrom has an efficient solution for the problematic pesticides. The methods used at RotaChrom can be easily extended to other input materials and target compounds (e.g., THC, CBG).

2021 Cannabis Extraction Virtual Conference

By Cannabis Industry Journal Staff
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2021 Cannabis Extraction Virtual Conference

Click here to watch the recording

Agenda

Hazards and Controls of Extraction with Liquified Petroleum Gases (LPG)

  • Alex Hearding, Chief Risk Management Officer, NCRMA

This presentation delves into how to identify the common hazards of extracting with LPG (butane and propane), understanding the where to find guidelines and standards for safe extraction practices and an introduction to best practices for: selecting equipment, extraction room construction, and filling LPG extraction equipment.

TechTalk: Environmental Monitoring in Cannabis Production and Processing

  • Tim Cser, Senior Technology Specialist, MilliporeSigma

Slow is Smooth & Smooth is Fast! Understanding the Kinetics & Thermodynamics of Cannabis Extraction

  • Dr. Markus Roggen, Founder & CEO, Complex Biotech Discovery Ventures (CBDV)

In this session, Dr. Roggen discusses how his lab undertook extensive experimental studies on the extraction behavior of various solvents. They analyzed thousands of real-world extractions, from various producers and for different instruments to build a machine learning algorithm that can optimize extraction processes autonomously.

TechTalk: A New Tool for Operational Compliance in the Cannabis Industry

  • Tony Martinez, Senior Vice President & General Manager, AuditPro

The Quest to Discover the Limits of CO2 Extraction

  • Jeremy Diehl, Co-Founder & CTO, Green Mill Supercritical

Learn why cannabis and hemp extraction is as much art as science, and how modifying and manipulating extraction methodologies and conditions can result in more refined products and significant cost savings.

TechTalk: Breaking the Limits with Solvent Recovery

  • Jürgen Heyder, Business Development Manager for Rotary Evaporation, Heidolph Instruments

The Future of Cannabis Concentrates: Developments in Hydrocarbon Extraction & Manufacturing

  • Michelle Sprawls, Laboratory Director, CULTA

Learn what closed loop hydrocarbon extraction is, what products you can make with this type of extraction method and what the advancements are for manufacturing and new techniques

Process Scale UP in the Cannabis/Hemp Industry

  • Darwin Millard, Committee Vice Chair, ASTM International

Darwin Millard provides real-world examples of the consequences of improper process scale up and the significance of equipment specifications, certifications and inspections, and the importance of vendor qualifications and the true cost of improper design specifications.

Click here to watch the recording

Recent Developments in Supercritical CO₂ Winterization

By Aaron Green
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Supercritical carbon dioxide (CO2) extraction is a processing technique whereby CO2 is pressurized under carefully controlled temperatures to enable extraction of terpenes, cannabinoids and other plant molecules. Once the extract is obtained the crude is often subjected to an ethanol winterization process to remove chlorophyll, fats and waxes.

Green Mill Supercritical is a Pittsburgh-based manufacturing and engineering company focused on cannabis and hemp extraction. The company offers a range of CO2 extraction equipment where users can tune and control their extraction methods. They recently announced  a technology advance enabling winterization in-process, which has the potential to remove the need for ethanol winterization.

We spoke with Jeff Diehl, director of marketing at Green Mill Supercritical, to learn more about the new process. Jeff was working in the tech industry in San Francisco in 2017 when he was invited to join Green Mill by his cousin, Jeremy Diehl, who is the founder and CTO.

Aaron Green: Before we get to your new technology, can you explain what industry trends you are watching?

Jeff Diehl: A big thing that I watch is the premium extract space. More and more consumers are demanding higher premium extracts. They want differentiated products. They want products that are safe and that have some kind of meaningful connection to the specific plant from which they came. Right now, CO2 plays a small role in the market for those products. Most premium products are generated through hydrocarbon extraction. So, I am watching how people are using CO2 to create the next generation of safe, premium products.

Aaron: What is the normal process for a CO2 extraction today?

Jeff Diehl, director of marketing at Green Mill Supercritical

Jeff: The current CO2 extraction process generally consists of two major phases to producing your final extract. In the first phase, you have extraction where you get your crude product. The second phase is post-extraction where you do cleanup to get your refined oil. Within that post-extraction phase, most operations include an ethanol-based winterization process.

Aaron: What does the winterization step do, exactly?

Jeff: Winterization is about removing waxes. Your main extraction is considered crude because it’s got a lot of materials from the plant that you don’t want. The large majority of unwanted material is waxes. Winterization is the process of using a solvent, traditionally ethanol, to separate the waxes from the cannabinoids. There are multiple challenges inherent in ethanol-based winterization that introduce cost, time and product loss. It’s terribly inefficient. Plus, there will always be residual ethanol left in your final product, and that’s not something consumers appreciate.

Aaron: You’ve recently announced a new process at Green Mill that moves the winterization step into the supercritical CO2 equipment. Can you explain how that works?

Jeff: With our process, which we call Real-Time Winterization, there is no ethanol involved in winterization anymore. It is all done with CO₂ during the primary extraction. That’s the major advance of our process and although it has been attempted before, no one has succeeded at doing it in a viable way. You take a process which is normally four days – one day for CO2 extraction and three days for ethanol winterization – and you do it all in less than a day. We have automated software, sensors and pumps that makes this all possible.

Aaron: How does the quality of the resulting product compare with the new process?

Jeff: You can see the difference right away, if you’re at all familiar with extraction. It just looks clean and bright. Lab analysis has been very positive thus far, but we continue to run tests. Our R&D team has done multiple tests, mostly on hemp and CBD. That’s because we don’t have a license for THC. We’re currently engaging with a licensed partner so that we can collect more data on THC-containing products, so we can give exact numbers. But with CBD, we’ve done multiple tests to validate the method and the technology, and are seeing consistently excellent results in regards to both purity of the product and efficiency of the process.

Aaron: How do yields compare between the processes?

Hemp CBD extract straight out of a Green Mill SFE Pro running Real-Time Winterization.

Jeff: From the data that we’ve seen in the industry, it looks like when you winterize with ethanol, you leave anywhere from 5 to 10% of your cannabinoids behind in the waxes. That’s just lost. With Real-Time Winterization using CO2 we have seen recovery rates as high as 99%. We are continuing to investigate that result with testing to make sure it was not an outlier, but in any case, recovery rates look promising.

Aaron: One of the other issues with ethanol is taxes and the ability to find food grade supply. Do you have any perspective you can share on that?

Jeff: There are a number of advantages to moving away from ethanol. The sheer quantity of ethanol is a factor. There are a lot of regulations and fire requirements around managing large quantities of ethanol. The ethanol winterization process itself is not just one process. There are multiple stages, from mixing, to freezing, to filtering, to removing the solvent. These are all opportunities for things to go wrong, so you’re always managing those risks. Multiple large pieces of equipment, including fume hoods, filter skids, cryo freezers and rotary evaporators, are expensive and require heavy management.

I think Elon Musk said the best process is no process. Anytime in an industrial process when you can remove steps in the process, that’s the direction you want to go in. And, that’s what we’ve done. With this recent work, we have effectively removed post processing for certain categories of end product.

Aaron: Do you have any patents on the new process?

Jeff: We have a patent pending on both the method and the equipment, which is allowing us to talk about this as much as we are.

Aaron: So, how does this work if somebody already owns an existing piece of Green Mill equipment? Is this something that can be retrofitted? Is it a software upgrade?

Jeff: There are two components. One is an equipment upgrade, which can be done retroactively for existing customers, and one is a methodology upgrade, which we assist our customers with. The automation software inherently can handle the settings that you need to run the methodology. In fact, it’s that software and the rest of our existing tech stack, the proprietary pump, the triple inline fractionation, the precision and stability of the overall system, that is what made this winterization advance possible.

Aaron: Where are you rolling this out first? And do you plan to go international?

Jeff: International is definitely in the plan, since we’ve already sold systems abroad. We are currently getting ready to announce the opening of our beta program with the new technology. So, we’re not ready to sell this widely at this time, but we are taking submissions from companies that want to get in early and join us at the forefront of CO₂ extraction innovation.

Aaron: Okay, great. Thanks Jeff, that’s the end of the interview.

extraction equipment

THC Remediation of Hemp Extracts

By Darwin Millard
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extraction equipment

Remediation of delta-9 tetrahydrocannabinol (d9-THC) has become a hot button issue in the United States ever since the Drug Enforcement Agency (DEA) released their changes to the definitions of marijuana, marijuana extract, and tetrahydrocannabinols exempting extracts and tetrahydrocannabinols of a cannabis plant containing 0.3% or less d9-THC on a dry weight basis from the Controlled Substances Act. That is because, as a direct consequence, all extracts and tetrahydrocannabinols of a cannabis plant containing more than 0.3% d9-THC became explicitly under the purview of the DEA, including work-in-progress “hemp extracts” that because of the extraction process are above the 0.3% d9-THC limit immediately upon creation.

The legal ramifications of these changes to the definitions on the “hemp extracts” marketplace will not be addressed. Instead, this article focuses on the amount of d9-THC that is available in the plant material prior to extraction and tracks a “hemp extract” from the point it falls out of compliance to the point it becomes compliant again and stresses the importance of accurate track-n-trace protocols at the processing facility. The model developed to support this article was intended to be academic and was designed to follow the d9-THC portion of a “hemp extract” through the lifecycle of a typical CO2-based extract from initial extraction to THC remediation. A loss to the equipment of 2% was used for each step.

Initial Extraction

For this exercise, a common processing scenario of 1000 kg of plant material at 10% cannabidiol (CBD) and 0.3% d9-THC by weight was modeled. This amount, depending on scale of operations, can be a facility’s total capacity for the day or the capacity for a single run. 1000 kg of plant material at 0.3% d9-THC has 3 kg of d9-THC that could be extracted, purified, and diverted into the marketplace. CO2 has a nominal extraction efficiency of 95%, meaning some cannabinoids are left behind in the plant material. The same can be said about the recovery of the extract from the equipment. Traces of extract will remain in the equipment and this little bit of material, if unaccounted for, can potentially open an operator up to legal consequences. Data for the initial extraction is shown in Image 1.

Image 1: Summary Data Table for Typical CO2-based Extraction of Phytocannabinoids

As soon as the initial extract is produced it is out of compliance with the 0.3% d9-THC limit to be classified as a “hemp extract”, and of the 3 kg of d9-THC available, the extract contains approx. 2.8 kg, because some of the d9-THC remains in the plant material and some is lost to the equipment.

Dewaxing via Winterization and Solvent Removal

Dewaxing a typical CO2 extract via winterization is a common process step. For this exercise, a wax content of 30% by weight was used. A process efficiency of 98% was attributed to the wax removal process and it was assumed that 100% of the loss can be accounted for in the residue recovered from the equipment rather than in the removed waxes. Data for the winterization and solvent recovery are shown in Image 2 and 3.

Image 2: Summary Data Table for Typical Winterization of a CO2 Extract
Image 3: Summary Data Table for Solvent Removal from a CO2 Extract

Two things occur during winterization and solvent removal, non-target constituents are removed from the extract and there is compounded loss from multiple pieces of process equipment. These steps increase the concentration of the d9-THC portion of the extract and produce two streams of noncompliant waste.

Decarboxylation & Devolatilization

Most cannabinoids in the plant material are in their acid form. For this exercise, 90% of the cannabinoids were considered to be acid forms. Decarboxylation is known to produce a mass difference of 87.7%, i.e. the neutral forms are 12.3% lighter than the acid forms. Heat was modeled as the primary driver and a process efficiency of 95% was used for the conversion rate during decarboxylation. To simplify the model, the remaining 5% acidic cannabinoids are presumed destroyed rather than degraded into other compounds because the portion of the cannabinoids which get destroyed versus degrade into other compounds varies from process to process.

Devolatilization is the process of removing low-molecular weight constituents from an extract to stabilize it prior to distillation. Since the molecular constituents of cannabis resin extracts vary from variety to variety and process to process, the extracts were assumed to consist of 10% volatile compounds. The model combines the decarboxylation and devolatilization steps to account for complete decarboxylation of the available acidic cannabinoids and ignores their weight contribution to the volatiles collected during devolatilization. Destroyed cannabinoids result in an amount of loss that can only be accounted for through a complete mass balance analysis. Data for decarboxylation and devolatilization are shown in Image 4.

Image 4: Summary Data Table for Decarboxylation and Devolatilization of a CO2 Extract

As the extract moves along the process train, the d9-THC concentration continues to increase. Decarboxylation further complicates traceability because there is both a known mass difference associated with the process and an unknown mass difference that must be calculated and justified.

Distillation

A two-pass distillation was modeled. On each pass a portion of the extract was removed to increase the cannabinoid concentration in the recovered material. Average data for distilled “hemp extracts” was used to ensure the model did not over- or underestimate the concentration of the cannabinoids in the distillate. The variables used to meet these data constraints were derived experimentally to match the model to the scenario described and are not indicative of an actual distillation. Data for distillation is shown in Image 5.

Image 5: Summary Data Table for Distillation of a Decarboxylated and Devolatilized Extract

After distillation, the d9-THC concentration is shown to have increased by 874% from the original concentration in the plant material. Roughly 2.2 kg of the available 3 kg of d9-THC remains in the extract, but 0.8 kg of d9-THC has either ended up in a waste stream or walking out the door.

Chromatography – THC Remediation Step 1

Chromatography was modeled to remove the d9-THC from the extract. Because there are several systems with variable efficiency rates at being able to selectively isolate the d9-THC peak from the eluent stream, the model used a 5% cut-off on the front-end and tail-end of the peak, i.e. 5% of the material before the d9-THC peak and 5% of the material after the d9-THC peak is assumed to be collected along with the d9-THC. Data for chromatography is shown in Image 6.

Image 6: Summary Data Table for d9-THC Removal using Chromatography

After chromatography, a minimum of three products are produced, compliant “hemp extract”, d9-THC extract, and noncompliant residue remaining in the equipment. The d9-THC extract modeled contains 2.1 kg of the available 3 kg in the plant material, and is 35% d9-THC by weight, an increase of 1335% from the distillation step and 11664% from the plant material.

CBN Creation – THC Remediation Step 2

For this exercise, the d9-THC extract was converted into cannabinol (CBN) using heat rather than cyclized into d8-THC, but a similar model could be used to account for this scenario. The conversion rate of the cannabinoids into CBN through heat degradation alone is low. Therefore, the model assumes half of the available cannabinoids in the d9-THC extract are converted to CBN. The entirety of the remaining portion of the cannabinoids are assumed to convert to some form of degradant rather than a portion getting destroyed. Data for THC destruction is shown in Image 7.

Image 7: Summary Data Table for THC Destruction through Degradation into CBN

Only after the CBN cyclization step has completed does the product that was the d9-THC extract become compliant and classifiable as a “hemp extract.”

Image 8: Summary Data Table for Reconciliation of the d9-THC Portion of the Hemp Extract

Throughout the process, from initial extraction to the final d9-THC remediation step, loss occurs. Of the 3 kg of d9-THC available in the plant material only 2.1 kg was recovered and converted to CBN. 0.9 kg was either lost to the equipment, destroyed in the process, attributable to the mass difference associated with decarboxylation, or was never extracted from the plant material in the first place. All of these potential areas of product loss should be identified, and their diversion risk fully assessed. Not every waste stream poses a risk of diversion, but some do; having a plan in place to handle waste the DEA considers a controlled substance is essential. Without a track-n-trace program following the d9-THC and identifying the potential risk of diversion would be impossible. The point of this is not to instill fear, instead the intention is to shed light on a very real issue “hemp extract” producers and state regulators need to understand to protect themselves and their marketplace from the DEA.

Advancements in Extraction & the Growth of the Concentrate Category

By Dr. Dominick Monaco
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Due to quick progressions in legalization, today’s cannabis industry bears little resemblance to the industry of five years ago. As the cannabis space gains mainstream acceptance, it resembles more “traditional” industries closely. In turn, how we consume cannabis has changed dramatically within this novel legal framework.

A brief visit to a cannabis dispensary quickly illuminates just how much the industry has changed in the past few years.

Within the dynamic of modern cannabis, perhaps no vertical has seen the same advancements as cannabis extracts. It’s precisely the growth of the concentrate category that has given rise to the many branded products that define the legal market.

To give a clear picture of how advancements in extraction have stimulated the concentrate category’s growth, we put together this brief exploration.

Standards & Technology

extraction equipmentBefore legalization, the production of cannabis extracts was a shady affair done in clandestine and often dangerous ways. Especially concerning BHO (Butane Hash Oil), home-based laboratories have long since been notorious fire hazards. Even more, with a total lack of regulation, black-market extracts are infamous for containing harmful impurities.

In the few short years that cannabis has been legal in Nevada, Washington and other states, extract producers have adopted standards and technology from more professional arenas. By borrowing from the food and pharmaceutical industries, concentrate companies have achieved excellence undreamed of a decade ago.

Good Manufacturing Practices

One of the essential elements in the extracts vertical advancements is the adoption of good manufacturing practices. According to the World Health Organization website, “Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.”

When adult-use cannabis was legalized in markets such as Colorado, cannabis companies were able to come out of the shadows and discuss GMPs with legit businesses. In doing so, they implemented professional controls on extract manufacturing in accordance with “quality standards” of state regulatory agencies.

Supercritical CO2 Extraction

As cannabis businesses adopted GMP from other industries, extract producers also embraced more sophisticated technology. Of these, supercritical CO2 has pushed the cannabis concentrates vertical into the future.

IVXX processingAccording to the equipment manufacturer Apeks Supercritical, “CO2 is considered to be a safer method of extraction because the solvent is non-volatile. The extract is purer because no trace of the solvent is left behind. It is also versatile and helps protect sensitive terpenes, by allowing cold separation.” By deriving methods from food production, supercritical equipment manufacturers have given cannabis companies a viable option for the commercial production of extracts.

Supercritical technology has helped push the concentrates vertical forward by providing a clean and efficient way to produce cannabis extracts. Nonetheless, supercritical CO2 equipment is highly sophisticated and carries a hefty price tag. Producers can expect to pay well over $100,000 for commercial supercritical CO2 extraction setup.

Products

Just as standards and technology have evolved in the cannabis extracts vertical, we have also seen products rapidly mature. Notably, the legal environment has allowed manufacturers to exchange ideas and methods for the first time. In turn, this dialogue has led to the development of new products, like isolates and live resin.

Isolates

Just as the name implies, isolates are concentrates made from a singular, pure cannabinoid. In today’s market, CBD isolates have grown increasingly popular because people can consume pure CBD without ingesting other cannabinoids or plant materials, including the legal 0.3% THC found in hemp.

Isolates are made by further purifying cannabis extracts in the process of purification, filtration and crystallization. As seen with other concentrates, isolates are used as the base for many cannabis products, such as gummies.

There is also growing interest in CBG isolate, which is another non-psychoactive cannabinoid when consumed orally.

Live Resin

The cannabis concentrate live resin has taken the industry by storm over the past few years. Live resin is a form of extract that is originally sourced from freshly harvested and frozen cannabis plants. The primary selling point behind this extract is the fact that fresh flowers produce much more vibrant aromas and flavors than dried cannabis. Interestingly, this pungency is tied to the preservation of terpenes in live resin.

Just a few of the dozens of various products types on the market today.

To make live resin, producers “flash freeze” fresh cannabis plants immediately after harvest. Valuable cannabinoids and terpenes are then extracted from the fresh, frozen plant material using hydrocarbon solvents. This whole process is done at extremely cold temperatures, ensuring no thermal degradation to the precious and volatile terpenes.

In lieu of these intricate steps to preserve the flower and extracts, live resin has continuously gained popularity. Namely because vaping with live resin is the best way to sample fresh cannabis terpene profiles in its most authentic fashion

It is amazing to see how much cannabis extracts have grown and progressed with legalization. Due to such amazing advancements in standards, technology, and products, the concentrates category has exploded on the dispensary scene. In today’s market, flowers have been largely sidelined in favor of concentrate-based products like gummies. These products now adorn dispensary shelves in beautiful packaging replete with purity and testing specifications.

It’s an often-overlooked fact that the purity standards of the legal extracts have made reliable cannabis brands possible in the first place. You cannot develop a cannabis brand without consistent products that customers can rely on; all things considered, it can be said that advancements in extraction have not only stimulated the concentrate category but the entire industry as we know it today.

Cannabis Extracts for the Informed Consumer: Solvent or Solventless

By Nick J. Bucci
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Editor’s Note: Nick Bucci is a freelance cannabis writer. You can view his work here 


As cannabis markets continue to gain traction, inconsistent and largely unpredictable markets have left recreational consumers in an informational fog. Try as the industry may, or may not to inform consumers, the lack of knowledge was evident when an established Colorado hash company opened a second operation in California. Expecting high demand for their solventless concentrates, the demand for their solvent-based counterparts came as a surprise. Initially hoping to eliminate solvent extracts from their product line-up, the company was forced to devote about half their overall production to solvent extracts, until information spreads and attitudes start to change. Over the past year several companies have joined the solventless side of history, but consumer understanding remains largely stagnant. For those immediately overwhelmed by terminology, cannabis extracts, concentrates or hash are all interchangeable terms describing concentrated cannabis. Under these umbrella terms, two distinct categories emerge depending upon whether chemical solvents were or were not used to extract the hash. Hence: solvent or solventless. A brief overview of cannabis concentrates will help consumers to understand the evolution away from solvent extractions and toward a superior solventless future.

ecxtractionfig2
Science and economics merge when considering all the possible uses of concentrated compounds to final product formulations

Before regulated cannabis markets, cannabis extracts had long been in use. These old-world methods of cannabis extraction use very basic solventless techniques to create more potent, concentrated forms of cannabis. Dry sifting is easily the oldest form of cannabis extraction and a prime example of one solventless technique. Something as simple as shaking dried cannabis over metal screens and collecting the residue underneath creates a solventless product called keif. Dark brown bubble-hash, made popular decades ago, is another ancient technique using only ice and water to perform extractions without chemical solvents. After decades of stagnant and limited old-world methods, changes in legislation allowed cannabis sciences to flourish. These old-world hash methods were quickly forgotten, replaced by the astonishing progress of modern solvent extractions.

Tetrahydrocannabinol (THC), just one of hundreds of cannabinoids found in cannabis.

The emergence of solvent extracts revolutionized cannabis around 2011, creating new categories of cannabis products that exploded onto the scene. Not only did solvent extracts produce the most potent and cleanest forms of hash ever seen at this point, it also created new possibilities for hash-oil vape cartridges and cannabis extract infused edibles. These solvent extracts use butane, propane, or other hydrocarbon solvents to extract, or “blast” cannabinoids from the plant. By running solvents through cannabis and then purging or removing leftover, residual solvents, a super-potent, premium hash product is achieved. Regulated markets require testing to ensure only a safe level, if any, of the solvent used in the extraction process remains in the final product. This technology ushered in the first wave of concentrates to medical and recreational markets under the descriptive titles of wax, shatter and crumble. While these effective and affordable products can still be found today, far superior products have largely replaced wax and shatter. Distillation techniques can further purify and isolate THC-a, while removing harmful residual solvents. For a time, Solvent-free was used to describe this ultra-purified distillate, but the needless term has fallen out of use. Solvent-free is still a solvent extraction using chemical solvents, don’t be fooled. Distillation and CO2 extractions have fallen into general disfavor as they destroy the flavorful terpenes and valuable cannabinoids, that when present create an “entourage effect.” This “entourage effect” happens when the medicinal and recreational properties are most effective, pronounced, and impactful due to a full range of terpenes and cannabinoids being present in the final product. With companies manually reintroducing terpenes to their final extracts, it’s an attempt to restore what was lost during solvent extraction processes. Many brands claim to use cannabis derived or food-grade terpenes to infuse or reintroduce terpenes into their purified hash oils. While this adds flavor and taste, especially to distillate cartridges, it’s far from an ideal solution. Armed with this new information, the informed consumer looks for a full profile of terpenes and cannabinoids in their hash.

THC-A crumble, terpene-rich vape oil, THC sap (from left to right).

With terpene preservation a new priority, all aspects of hash making were reevaluated. By using fresh-frozen cannabis flower, solvent extractions quickly reached new heights. Using the same techniques as prior solvent extractions, the cannabis plant is frozen immediately upon harvesting, rather than trimming and drying the crop as usual. Freezing the plant preserves valuable terpenes helping to create a new category for hydrocarbon extracts under the general label of live resins. This live resin, containing vastly greater profiles of terpenes and cannabinoids than earlier waxes, shatters or crumbles is sold as live-resin sauce, sugar, badder, frosting, diamonds and more. Many versions of live resin re-use previous terms that describe consistencies. These live resin solvent extracts outperform the wax, crumble and shatters of old, and are priced accordingly. Some of the best solvent extracts available today use butane to extract hash oil, which forms THC-a crystals and diamonds seen in live resin sauces. Having learned the value of terpenes and cannabinoids, early efforts to purify THC were clearly misled. The industry defining use of fresh-frozen cannabis flowers greatly improved the quality of all extracts having realized the psychoactive effects are largely dependent on the various profiles of cannabinoids and terpenes. Pure THC-a crystals and isolates are easily achieved with solvent extractions but, produce inferior effects both medicinally and recreationally. Discovering the “entourage effect” as described earlier, these elements of cannabis allowed old-world solventless techniques to be re-inspired and reinvigorated with the benefit of healthy genetics and a hearty understanding of past mistakes.

Having gone full circle, solventless techniques are again at the forefront of the cannabis industry, having attained near perfection for our current understanding of cannabis anatomy.

figure1 extract
The increasingly finer mesh works to separate and extract microscopic trichomes

Using the lessons and tendencies of prior extractions, the solventless method, in all its final forms, begin with the same initial process to make ice-water hash oil. Often referred to as solventless hash oil (SHO), fresh-frozen flowers are submerged in ice and water, soaked and agitated before the water is filtered through mesh screens. As these mesh screens are measured by microns, the increasingly finer mesh works to separate and extract microscopic trichomes that break free from the cannabis plant. The 120- and 90-micron mesh screens usually collect pristine trichome heads. After scraping the remaining material from the screens, its sieved onto trays where the hash can dry using modern techniques of sublimation. The results are beyond phenomenal and are sure to shock even life-long cannabis consumers. This technique isolates only the most potent and psychoactive parts of the plant, to produce white to clear solventless ice water hash. When done with precision 6-star ice water hash is formed. The hash can be sold and consumed as is or undergo additional solventless techniques to produce hash-rosin. Not to be confused with live-resins, rosin uses pressure and slight heat to squeeze ice-water hash, into hash-rosin. Some companies have elected to whip their rosins into a solventless badder or allow their hash rosins to undergo a cold cure process that creates textures and varieties like hash rosin sauce. Regardless of the final solventless product, they all begin as ice water extractions. These simple, natural methods of extraction are quickly being adopted by companies known for live resin. As solventless extracts are safer, cleaner and superior in quality to solvent chemical extractions, the race is on as the industry shifts toward a solventless future.

While I’d be happy to never see another solvent extract again, without the miraculous breakthroughs and advances in all aspects of cannabis manufacturing and production we may have not yet arrived where we are today. When using solvents to extract, the trichomes, which contain the full spectrum of terpenes and cannabinoids, are dissolved by the solvent, which is then evaporated off, leaving behind dissolved trichomes. In solventless hash, these trichomes remain whole and are never dissolved or broken down. Instead they are broken free by agitation in ice and water, separating the trichome heads from their less-active stems. These valuable trichomes heads contain everything pertinent and are never destroyed, dissolved or melted like solvent-extractions are forced to do. The benefit of keeping the heads of these trichomes whole results in a far superior product expressing the full profile of terpenes and cannabinoids the way mother nature intended. This natural profile of trichomes lends itself directly to the entourage effect that solvent extracts were found to be missing.

Extraction techniques are not equal and depend upon whether quality or mass production is the aim. Solvent extracts have quickly begun to represent the old-guard of mass-produced cannabis concentrates, with the solventless new-guard focusing on quality, small batch, hash-rosin excellence.

dry cannabis plants

How to Grow Cannabis Plants for Concentrate Production

By Andrew Myers
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dry cannabis plants

While flower is still the most popular way to consume cannabis, the concentrates market is booming. Some predict concentrates will be nearly as popular as flower by 2022, with an estimated $8.5 billion in retail sales. That’s a lot of concentrates and, chances are, cannabis producers are already feeling the pressure to keep up.

Concentrates refer to products made from processing cannabis – often resulting in much higher THC or CBD percentages. The category includes oils, wax, dabs, shatter, live resin and hash. Consumers are increasingly drawn to these cannabis products for their near-immediate and intense effects. They’re often consumed through vaporization, dabbing or sublingual absorption and are sometimes favored by those who want to avoid smoking. Cannabis growers who have traditionally focused on flower yields may decide to prioritize quality and potency levels in order to tap into these changing consumer tastes.

What Growers Should Focus on to Produce High Quality Concentrates
We’ll let you in on a little secret: making good concentrates starts with good flower. If you’re starting with low-quality flower, it’s impossible to create a high-quality concentrate. Whatever qualities inherent to the flower you’re starting with will be amplified post-processing. So, really, the concentrate-making process starts at the seedling level, requiring the right care and attention to coax out the results you’re looking for.

Tetrahydrocannabinol (THC), just one of hundreds of cannabinoids found in cannabis.

But what makes good flower? While this can be a subjective question, those producing concentrates generally look for flowers with big, abundant trichomes. Trichomes are the small, dewy structures found across the cannabis plant on buds, leaves and even the stem. They’re responsible for producing the plant’s cannabinoids and terpenes – the chemical compounds that give a strain its unique benefits, aroma and taste. Evolutionarily, trichomes attract pollinators, deter hungry herbivores and provide some defense against wind, cold and UV radiation.

Generally, trichomes indicate how potent the flower is. Plus, what we’re most often looking for when making concentrates is higher cannabinoid and terpene profiles, while also ensuring absolute safety.

What measures can growers take to produce crops that are ideal for concentrate production? Start with the following:

Avoiding Contaminants
Just like you would wash your fruits and vegetables before consumption, consumers want to be sure there’s no dangerous residuals in the concentrate they are ingesting. Growers can avoid any post-process residuals by taking a few key steps, including:

  • Photo: Michelle Tribe, Flickr

    Cutting out the pesticides. Any pesticides that are on your flowers before they go through processing will show up in your concentrates, often even more – you guessed it – concentrated. This is a serious health concern for consumers who might be sensitive to certain chemicals or have compromised immune systems. It’s dangerous to healthy consumers, too. Rather than spraying hazardous chemicals, growers could consider integrated pest management techniques, such as releasing predatory insects.

  • Limiting foliar spraying. Some growers will use foliar spraying to address nutrient deficiency or pest-related issues through delivering nutrients straight to the leaves. However, this can also result in contaminated concentrates. If you really need to spray, do it during the vegetative stage or investigate organic options.
  • Taking the time to flush the crop. This is a critical step in reducing potential contaminants in your concentrate, especially if you’re using a non-organic nutrient solution or fertilizer. Flushing simply means only giving your plants water during the final two weeks of flowering before harvest, resulting in a cleaner, non-contaminated flower and therefore a cleaner concentrate.

Perfecting the Indoor Environment
When cultivating cannabis indoors, growers are given ultimate control over their crop. They control how much light the plants receive, the lighting schedule, temperature and humidity levels. Creating the ideal environment for your cannabis crop is the number one way to ensure healthy plants and quality concentrates. There are many factors to consider when maintaining an indoor grow:

  • Temperature regulation. Trichomes are sensitive to temperature changes and start to degrade if they’re too hot or too cold. To maintain the best trichome structure, you’ll want to maintain an ideal temperature – for most strains, this falls between an idyllic 68 and 77 degrees.
  • Adequate light. For plants to perform photosynthesis indoors, they’ll need an appropriate light source – preferably one that is full-spectrum. Full-spectrum LEDs are able to closely replicate the sun and provide ample, uniform light to your crop. Another selling point for LEDs is their low heat output, making it much easier for growers to regulate ambient heat.

    dry cannabis plants
    Rows of cannabis plants drying and curing following harvest
  • CO2. Another necessary ingredient for photosynthesis is CO2. Providing your indoor crops with CO2 can boost plant size and yields and, therefore, provides more surface area for trichomes to develop and thrive.
  • Cold snap prior to harvest. Some growers rely on this age-old tactic for one last push before harvest – lowering their temperature for a few days right at the end of the flower cycle. They believe this puts the plants into a defense mode and will produce more trichomes in order to protect themselves.

Following Best Practices Post-Harvest
You made it to harvest – you’re almost done!

When harvesting and storing your plants, handle them with care to reduce damage to trichomes. If you’re planning on immediately making concentrates, you can move forward to the drying and curing process. If you’re going to wait a few weeks before processing, freeze your plants. This will preserve the cannabinoid and terpene profiles at their peak.

As the cannabis industry continues to expand, more consumers are likely to reach for concentrates at their local dispensaries. It makes sense that businesses want to diversify their offerings to satisfy customers looking for the most effective way to consume cannabis. As with any cannabis-derived product, producers will want to prioritize quality and safety – especially in the concentrate market.

Managing Cannabis Waste and Protecting Your Business from Risk

By David Laks
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Cannabis producers know that they cannot treat plant waste like common yard waste. They need to develop a detailed waste disposal plan in order get a license to operate.

Failing to follow the approved plan and improperly disposing of dry waste materials and waste products from oil extraction leads to fines, liabilities or even having your license rescinded.

Learning to deal with cannabis waste appropriately is crucial to the success of an operation. There are a number of strict controls in place for dealing with any kind of hazardous waste, which can’t just be sent to a landfill or composting facility.

In the US, the EPA and state governments provide guidelines for disposing of hazardous waste properly, and other countries have federal and local requirements as well. The EPA, like other environmental bodies, differentiates between two types of waste: solid and liquid.

Solid waste disposal: The guideline for identifying solid waste is that it’s “unrecognizable and unusable.” This means no one should be able to look at a bag of waste and know immediately that it is cannabis. Many cannabis operations have a facility on site for grinding down the waste into smaller bits. If the waste is non-hazardous, it is mixed with other non-cannabis organics such as garden trimmings and then composted or sent to the appropriate landfill. If it’s hazardous, it’s mixed with cat litter, sand, plastic or sawdust and sent to the appropriate landfill.

Liquid waste disposal: Liquid waste is a bit more complicated. It must be disposed of properly or sent to a hazardous waste treatment facility. Cannabis operations must partner with a shipping company to dispose of the hazardous waste appropriately, unless they transport it themselves.

It can be confusing to manage the risks of proper disposal of cannabis waste. Keep it simple by following these three tips:

  1. Become an expert in all the legal restrictions – and follow them. Federal restrictions will guide you overall, but local (i.e., state and municipal) restrictions are equally important and may vary.
  2. Seek out experienced, reputable disposal companies – and hire the best one.Look for one that is familiar with handling hazardous waste in general and cannabis waste in particular.
  3. Familiarize yourself with the guidelines for proper tracking, transportation and sign-offs – and follow them.Completing all appropriate documentation ensures you have a paper trail to protect you in the event of an audit. Much of the documentation creates a written record so inspectors can confirm appropriate handling.

Waste disposal policies should be reviewed regularly as state and municipal regulations can change. At the same time, it would be wise to review your environmental insurance policy to ensure your business is covered for any accidental releases.

It can be tempting to take shortcuts – saving both money and time – when it comes to hazardous waste disposal. But properly disposing of hazardous materials can demonstrate your organization’s credibility and financial wellbeing, and it can also save you from unnecessary risk.

From The Lab

I Was Wrong… und das ist auch gut so!

By Dr. Markus Roggen
3 Comments

I was wrong. And that’s a good thing! Based on all available data, I assumed that evaporating ethanol from a cannabis oil/ethanol solution would result in terpene loss. As it turns out, it doesn’t. There are so many beliefs and assumptions about cannabis: Cannabis cures cancer!1 Smoking cannabis causes cancer!2 Sativas help you sleep; Indicas make you creative!3,4 CBD is not psychoactive!5 But are these ‘facts’ backed by science? Have they been experimentally tested and validated?

I postulated a theory, designed experiments to validate it and evaluated the results. Simply putting “cannabis backed by science” on your label does not solve the problem. Science is not a marketing term. It’s not even a fixed term. The practice of science is multifaceted and sometimes confusing. It evolved from the traditional model of Inductivism, where observations are used in an iterative process to refine a law/theory that can generalize such observations.6 Closely related is Empiricism, which posits that knowledge can only come from observation. Rationalism, on the other hand, believes that certain truths can be directly grasped by one’s intellect.7 In the last century, the definition of science was changed from the method by which we study something, such as Inductivism or Rationalism, and refocused on the way we explain phenomena. It states that a theory should be considered scientific if, and only if, it is falsifiable.8 All that means is that not the way we study something is what makes it scientific, but the way we explain it.

I wonder how can we use empirical observations and rational deliberations to solve the questions surrounding cannabis? And more importantly, how can we form scientific theories that are falsifiable? Cannabis, the plant, the drug, has long been withheld from society by its legal status. As a result, much of what we know, in fact, the entire industry has thrived in the shadows away from rigorous research. It’s time for this to change. I am particularly concerned by the lack of fundamental research in the field. I am not even talking about large questions, like the potential medical benefit of the plant and its constituents. Those are for later. I’m talking about fundamental, mundane questions like how many lumens per square centimetre does the plant need for optimal THC production? What are the kinetics of cannabis extraction in different solvents? What are the thermodynamics of decarboxylation? Where do major cannabinoids differ or align in terms of water solubility and viscosity?

The lack of knowledge and data in the cannabis field puts us in the precarious position of potentially chasing the wrong goals, not to mention wasting enormous amounts of time and money. Here’s a recent example drawn from personal experience:Certainly, I cannot be the only one who has made an incorrect assumption based on anecdotes and incomplete data?

Some of the most common steps in cannabis oil production involve ethanol solutions. Ethanol is commonly removed from extraction material under reduced pressure and elevated heat in a rotary evaporator. I expected that this process would endanger the terpenes in the oil – a key component of product quality. My theory was that volatile terpenes9 would be lost in the rotary evaporator during ethanol10 removal. The close values of vapor pressure for terpenes and ethanol make this a reasonably assumed possibility.11 In the summer of 2018, I finally got the chance to test it. I designed experiments at different temperatures and pressures, neat and in solution, to quantify the terpene lost in ethanol evaporation. I also considered real life conditions and limitations of cannabis oil manufacturers. After all the experiments were done, the results unequivocally showed that terpenes do not evaporate in a rotary evaporator when ethanol is removed from cannabis extracts.12 As it turns out, I was wrong.

We, as an industry, need to start putting money and effort into fundamental cannabis research programs. But, at least I ran the experiments! I postulated a theory, designed experiments to validate it and evaluated the results. At this point, and only this point, can I conclude anything about my hypothesis, even if that is that my working theory needs to be revised. Certainly, I cannot be the only one who has made an incorrect assumption based on anecdotes and incomplete data?

There is a particular danger when using incomplete data to form conclusions. There are many striking examples in the medical literature and even the casual observer might know them. The case of hormone replacement therapy for menopause and the associated risks of cardiovascular diseases showed how observational studies and well-designed clinical trials can lead to contradicting results.13 In the thirties of the last century, lobotomy became a cure-all technique for mental health issues.14 Dr. Moniz even won the Nobel Prize in Medicine for it.15 And it must come as no surprise when WIRED states “that one generation’s Nobel Prize-winning cure is another generation’s worst nightmare.”16 And with today’s knowledge is impossible to consider mercury as a treatment for syphilis, but that is exactly what it was used as for many centuries.17 All those examples, but the last one in particular should “be a good example of the weight of tradition or habit in the medical practice, […] of the necessity and the difficulties to evaluate the treatments without error.”18 There is the danger that we as cannabis professionals fall into the same trap and believe the old stories and become dogmatic about cannabis’ potential.

We, as an industry, need to start putting money and effort into fundamental cannabis research programs. That might be by sponsoring academic research,19 building in-house research divisions,20 or even building research networks.21 I fully believe in the need for fundamental cannabis research, even the non-sexy aspects.22 Therefore, I set up just that: an independent research laboratory, focused on fundamental cannabis research where we can test our assumptions and validate our theories. Although, I alone cannot do it all. I likely will be wrong somewhere (again). So, please join me in this effort. Let’s make sure cannabis science progresses.


References

  1. No, it does not. There are preliminary in-situ studies that point at anti-cancer effects, but its more complicated. The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report, Abrams, Donald I., European Journal of Internal Medicine, Volume 49, 7 – 11
  2. No, it does not. National Academies of Sciences, Engineering, and Medicine. 2017. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press. https://doi.org/10.17226/24625.
  3. No, it does not. The chemical profile of the plant dictates the biological effects on humans, not the shape of the leaf.  Justin T. Fischedick, Cannabis and Cannabinoid Research, Volume: 2 Issue 1: March 1, 2017
  4. Indica and Sativa are outdated terms. Piomelli D, Russo EB. The Cannabis sativa versus Cannabis indica debate: An Interview with Ethan Russo, MD. Cannabis Cannabinoid Res 2016; 1: 44–46.
  5. No, it is. CBD’s supposed “calming effects” is indeed a psychoactive effect. However, it is not intoxicating like THC. Russo E.B., Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects.Br. J. Pharmacol. 2011; 163: 1344-1364
  6. As attributed to Francis Bacon.
  7. See the work by philosopher Baruch Spinoza.
  8. As theorized by Karl Popper.
  9. Monoterpenes have a vapor pressure in the low to mid hundreds of Pascals at room temperature.
  10. Vapor pressure of 5.95 kPa at 20˚C.
  11. Furthermore, there is always the possibility of azeotropes in complex mixtures. Azeotropes are mixtures of two or more liquids that have different boiling points individually, but in mixture boil together.
  12. Terpene Retention via Rotary Evaporator Application Note, Heidolph North America
  13. https://www.pharmaceutical-journal.com/research/review-article/establishing-the-risk-related-to-hormone-replacement-therapy-and-cardiovascular-disease-in-women/20202066.article?firstPass=false
  14. https://psychcentral.com/blog/the-surprising-history-of-the-lobotomy/
  15. https://en.wikipedia.org/wiki/António_Egas_Moniz
  16. https://www.wired.com/2011/03/lobotomy-history/
  17. https://www.infezmed.it/media/journal/Vol_21_4_2013_10.pdf
  18. https://www.ncbi.nlm.nih.gov/pubmed/11625051
  19. Canopy Growth funds a professorship of cannabis science at UBC. Tilray collaborates with UCSD on a phase I/II clinical trial.
  20. For examples see: NIBR, PMISCIENCE.
  21. For examples see: CEMI, theAIRnet, Future Sky.
  22. Research that does not lead to short-term stock value spikes but long-term progress

A More Effective and Efficient Approach to Purer Cannabidiol Production Using Centrifugal Partition Chromatography

By Lauren Pahnke
3 Comments

Many physicians today treat their patients with cannabidiol (CBD, Figure 1), a cannabinoid found in cannabis. CBD is more efficacious over traditional medications, and unlike delta-9 tetrahydrocannbinol (THC), the main psychoactive compound in cannabis, CBD has no psychoactive effects. Researchers have found CBD to be an effective treatment for conditions such as cancer pain, spasticity in multiple sclerosis, and Dravet Syndrome, a form of epilepsy.

CBD is still considered an unsafe drug under federal law, but to meet the medical demand, 17 states in the US recently passed laws allowing individuals to consume CBD for medical purposes. A recent survey found that half of medicinal CBD users rely on the substance by itself for treatment. As doctors start using CBD to treat more patients, the demand for CBD is only expected to rise, and meeting that demand can pose challenges for manufacturers who are not used to producing such high quantities of CBD. Furthermore, as CBD-based drugs become more popular, the US Food and Drug Administration (FDA) will likely require manufacturers to demonstrate they can produce pure, high-quality products.

cannabidiol
Figure 1. The structure of cannabidiol, one of 400 active compounds found in cannabis.

Most manufacturers use chromatography techniques such as high performance liquid chromatography (HPLC) or flash chromatography to isolate compounds from natural product extracts. While these methods are effective for other applications, they are not, however, ideal for CBD isolate production. Crude cannabis oil contains some 400 potentially active compounds and requires pre-treatment prior to traditional chromatography purification. Both HPLC and flash chromatography also require silica resin, an expensive consumable that must be replaced once it is contaminated due to irreversible absorption of compounds from the cannabis extract. All of these factors limit the production capacity for CBD manufacturers.

Additionally, these chromatography methods use large quantities of solvents to elute natural compounds, which negatively impacts the environment.

A Superior Chromatography Method

Centrifugal partition chromatography (CPC) is an alternative chromatography method that can help commercial CBD manufacturers produce greater quantities of pure CBD more quickly and cleanly, using fewer materials and generating less toxic waste. CPC is a highly scalable CBD production process that is environmentally and economically sustainable.

The mechanics of a CPC run are analogous to the mechanics of a standard elution using a traditional chromatography column. While HPLC, for instance, involves eluting cannabis oil through a resin-packed chromatography column, CPC instead elutes the oil through a series of cells embedded into a stack of rotating disks. These cells contain a liquid stationary phase composed of a commonly used fluid such as water, methanol, or heptane, which is held in place by a centrifugal force. A liquid mobile phase migrates from cell to cell as the stacked disks spin. Compounds with greater affinity to the mobile phase are not retained by the stationary phase and pass through the column faster, whereas compounds with a greater affinity to the stationary phase are retained and pass through the column slower, thereby distributing themselves in separate cells (Figure 2).

Figure 2- CPC
Figure 2. How CPC isolates compounds from complex, natural mixtures. As the column spins, the mobile phase (yellow) moves through each cell in series. The compounds in the mobile phase (A, B, and C) diffuse into the stationary phase (blue) at different rates according to their relative affinities for the two phases.

A chemist can choose a biphasic solvent system that will optimize the separation of a target compound such as CBD to extract relatively pure CBD from a cannabis extract in one step. In one small-scale study, researchers injected five grams of crude cannabis oil low in CBD content into a CPC system and obtained 205 milligrams of over 95% pure CBD in 10 minutes.

Using a liquid stationary phase instead of silica imbues CPC with several time and cost benefits. Because natural products such as raw cannabis extract adhere to silica, traditional chromatography columns must be replaced every few weeks. On the other hand, a chemist can simply rinse out the columns in CPC and reuse them. Also, unlike silica columns, liquid solvents such as heptane used in CPC methods can be distilled with a rotary evaporator and recycled, reducing costs.

Environmental Advantages of CPC

The solvents used in chromatography, such as methanol and acetonitrile, are toxic to both humans and the environment. Many environmentally-conscious companies have attempted to replace these toxic solvents with greener alternatives, but these may come with drawbacks. The standard, toxic solvents are so common because they are integral for optimizing purity. Replacing a solvent with an alternative could, therefore, diminish purity and yield. Consequently, a chemist may need to perform additional steps to achieve the same quality and quantity achievable with a toxic solvent. This produces more waste, offsetting the original intent of using the green solvent.

CPC uses the same solvents as traditional chromatography, but it uses them in smaller quantities. Furthermore, as previously mentioned, these solvents can be reused. Hence, the method is effective, more environmentally-friendly, andeconomically feasible.

CPC’s Value in CBD Production

As manufacturers seek to produce larger quantities of pure CBD to meet the demand of patients and physicians, they will need to integrate CPC into their purification workflows. Since CPC produces a relativelyduct on a larger scale, it is equipped to handle the high-volume needs of a large manufacturer. Additionally, because it extracts more CBD from a given volume of raw cannabis extract, and does not use costly silica or require multiple replacement columns, CPC also makes the process of industrial-scale CBD production economically sustainable. Since it also uses significantly less solvent than traditional chromatography, CPC makes it financially feasible to make the process of producing CBD more environmentally-friendly.

Suggested Reading:

CPC 250: Purification of Cannabidiol from Cannabis sativa

Introduction to Centrifugal Partition Chromatography