Cannabidiol, or CBD, is the new star of functional ingredients. It is a food, medicine, saviour of the farmers, even a health elixir.
The cannabis and hemp industries have recently experienced extreme growth and progress in all fields. Countries, states and countries are legalizing hemp and/or cannabis, cannabinoid producers see unpreceded business growth, new treatment option for various conditions are researched and approved. But while the markets are growing, hemp and cannabis producers are suffering. An overproduction depresses commodity prices, and inefficient processes squeeze the profit margins. Additionally, hemp and cannabis products require high purity of cannabinoid ingredients, both from a regulatory level and for patient care.
This presentation will cover the latest research on CBD isolation, from its solubility behaviour in common extraction solvents to purification via crystallization. Our latest findings in understanding, controlling, and optimizing cannabis production in analytics, processing, extraction and formulation are presented. The collaborative effort of the multidisciplinary research team at Delic Labs led to a diverse set of insight in every stage of production.
2. Introduction
DELIC Labs is a research venture that seeks to add fundamental
scientific insight to the field of cannabis and mushroom
production.
We seek to support the cannabis and mushroom industries by
establishing a centralized hub in Vancouver, BC, for collaborative
research focused on:
• Process Design
• Process Optimization
• Process Analytics
• Formulation Research
3. Collaborative Research
DELIC Labs collaborates with academic, industry and private
groups around the globe. Some highlights of those collaborations
are:
• University of British Columbia, Vancouver
• Loyalist College, Belleville
• Via Innovations by Dr. Monica Vialpando
• Veridient Science by Dr. Linda Klumpers
Fundamental Collaboration
4. Research Topics
• Chemometrics and data analytics for process control and
optimization
• Kinetic studies to understand mechanisms
• In-process analytics for process control
• Computational studies to understand mechanisms
• Process development, like crystallization
Fundamental Cannabis and Mushroom Chemistry
5. 3
Outline
- CBD, an introduction
- Cannabinoids and contaminants
- Solubility in common extraction solvents
- Crystallization
7. Hemp vs. Cannabis: Genetics
• Genetic difference between hemp and drug type cannabis
• Hemp and cannabis are not different species, as they can
interbreed
• No indication about 0.3%wt. THC level, yet!
• No genetic base for legal limit of 0.3%wt. THC
• No genetic difference between Sativa and Indica
8. Hemp vs. Cannabis: Regulations
• FDA enforces:
• Medical claims
• THC levels
• Don’t ask the DEA
• Levels are arbitrary:
• USA: 0.3%wt. THC
• South Carolina: 0.5%wt. THC
• Switzerland: 1%wt. THC
• The 0.3%wt. THC limit is binding for all product forms
• Sale of >0.3%wt. THC is illegal, but B2B still happens
14. Extraction
• The goal is to separate the
desired compounds from the
cannabis plant matrix
• Various Solvent Systems
• Supercritical CO2
• Alcohol (mainly EtOH)
• Hydrocarbon (mainly Butane)
18. Extraction: CO2 Precision
• Neutral cannabinoids are more soluble
than acid form
• THC > THCA
• CBD more soluble than THC
19. Hemp Extract
Extraction: Solvents
• Alcohols: EtOH, iPrOH
• Very Fast
• Scalable, affordable instrumentation
• Little control about extract
Hemp Flower
>0.3% THC
20. Extraction: EtOH Precision
• EtOH: CBD more soluble than THC
• Aliphatic: THC more soluble than CBD
doi.org/10.1021/acs.jafc.0c01161
21. Extraction: Solvents
• Hydrocarbons: butane, propane
• Fast
• Instrumentation and facility require safety rating
• Can extract wet flower
Hemp Flower Hemp Extract
>0.3% THC
24. Crystallization
• Formation of solids, with highly organized
structure of atoms or molecules.
• Influenced by temperature, air pressure, and time of
fluid evaporation.
• Size and shape of crystals depend on cooling rate.
25. R² = 0.9646
R² = 0.9705
50
150
250
350
450
550
650
750
0 4 8 12 16 20 24 28 32 36 40
Concentration
(mg/ml)
Temperature (°C)
Cloud point
Clear point
• Clear points: temperature at which all material is dissolved
• Cloud point: temperatures at which crystals are present
• Two important curves:
• Metastable Zone Width (MSZW): Control crystallization process
with cooling rate for purity, yield, and particle size.
CBD, MSZW, Graphs
Clear
points
Cloud
point
Everything
dissolved
Everything
crashed out
MSZW
Cooling
Rate
26. Crystal16
• Benchtop multi-reactor instrument
• High through-put crystallization experiments
• 16 simultaneous crystallization reactors
• Integrated transmissivity sensors
• Rapid generation of solubility data and MSZW
28. Crystallization in n-Pentane
• Current favorite due its high vapor pressure and low boiling point
• <10°C, CBD: higher solubility -> lower crystallization yield
• Very narrow MSZW -> nucleation difficult
• Low b.p. & max. solubility: more solvent required at scale
R² = 0.9462
R² = 0.9603
50
150
250
350
450
550
650
750
0 4 8 12 16 20 24 28 32 36 40
Concentration
(mg/ml)
Temperature (°C)
Cloud Point
Clear Point
29. R² = 0.9627
R² = 0.9698
50
150
250
350
450
550
650
750
0 4 8 12 16 20 24 28 32 36 40
Concentration
(mg/ml)
Temperature (°C)
Cloud Point
Clear Point
Crystallization in n-Hexane
• b.p. (69°C) ~2x n-pentane
• Solubility profile between 5°C - 20°C similar
• Solubility dramatically increases >20°C, max. ~12.370 g/ml
• MSZW larger -> more control over seed nucleating
• n-hexane: neurotoxic, environment hazards
30. R² = 0.9646
R² = 0.9705
50
150
250
350
450
550
650
750
0 4 8 12 16 20 24 28 32 36 40
Concentration
(mg/ml)
Temperature (°C)
Cloud point
Clear point
Crystallization in n-Heptane
• Moderate CBD solubilization ability 5°C – 35°C
• Highest b.p. at 98.4°C and large solubility (~88 g/mL)
• ~50°C is recommended
• The MSZW comparable to n-hexane
• No known risks to humans or environment
31. R² = 0.9696
R² = 0.9545
0
3
6
9
12
15
18
10.0 15.0 20.0 25.0 30.0 35.0 40.0
THC
wt
%
Temperature (°C)
Cloud Point
Clear Point
Crystallization with THC in n-Heptane
• Real life example: Various [THC] at CBD ~400 mg/mL
• THC does not co-crystallize but acts as ‘good’ solvent by
increasing solubility of CBD
• THC acts as crystal surface impurity, remove with washing
• Low temp’s for same yield
• No ‘one-size-fits-all’ recipe
32. Conclusion
• Three popular hydrocarbon solvents (n-pentane, n-hexane, and n-
heptane) were investigated for CBD purification by crystallization.
• Similar polarity, but, significant differences in crystallization
parameters
• n-Pentane: highest vapor pressure, faster drying, large solvent volumes
required, narrow MSZW
• n-Hexane: Medium b.p., high CBD loading capacity, harm to human &
environment
• n-Heptane: High b.p., medium CBD loading capacity, best safety profile due
to lower vapor pressure
• THC acts as a ‘good’ solvent
• increases solubility of CBD
• reduces crystallization temperatures
33. Expertise
CSO: Dr. Markus Roggen
Dr. Roggen has been actively involved in the cannabis industry for over 5 years in executive positions
executive positions overseeing production, R&D and process optimization for multiple producers. Dr.
multiple producers. Dr. Roggen is also a trusted advisor and mentor for multiple startups, startup
startups, startup accelerators and organizations.
DELIC LabsTeam
Our team covers a wide range of expertise,
including analytical chemistry, process chemistry,
engineering physics, data science and statistics.
ScientificAdvisor: Prof.GlennSammis
Prof. Sammis is a Full Professor in the Chemistry Department at the University of British Columbia. He
has built an internationally recognized research group working on the development of novel synthetic
methods for the preparation of natural products and pharmaceuticals.
