CBD isolate crystallization FAQ

What is CBD isolate?

Cannabidiol (CBD) isolate is hemp-industry nomenclature for crystalline cannabidiol. It is cannabidiol in its purest form and its appearance (when pure) is that of an off-white crystalline solid. It is referred to as CBD isolate because CBD is one component of a multi-component extract that has been ‘isolated’ from all the others.

How is it made?

There are several steps required to take the cannabis biomass ‘from crop to crystal’. These steps will vary depending on the user’s preferred extraction method, but typically the steps are as follows:

  1. Cultivation
    the growing and harvesting of the plant
  2. Extraction
    the extraction of the crude oil from the biomass (commonly using CO2 or cryogenic ethanol)
  3. Winterisation
    the removal of waxes/lipids/proteins from the crude oil
  4. Distillation
    the purification of the winterised crude oil into a refined, concentrated CBD oil (often referred to as ‘CBD distillate’)
  5. Isolation
    the crystallization of the CBD molecules from the CBD distillate to produce crystalline cannabidiol (CBD isolate)
  6. Filtration, washing and drying
    physical separation of the residual distillate and solvent from which the CBD isolate was crystallised
  7. Packaging
    the packaging of the CBD isolate to provide the final product.

NiTech® continuous crystallizers are for Step 5 – the crystallization of CBD isolate:
the crystallization of CBD molecules from CBD distillate, to form CBD isolate.

If you also require assistance with step 6, the filtration, washing and drying of CBD isolate, we recommend our friends at Alconbury Weston Ltd (AWL)


CBD from crop to crystal steps

How does CBD crystallization work?

To understand this, we first have to explain crystallization. At its base level, crystallization is the isolation of a solute from a solvent by causing it to form a solid. This is achieved by manipulating the solute’s solubility in the solvent. The most common way to achieve this is through the manipulation of temperature. This is referred to as a cooling crystallization and this is what is used to crystallize CBD isolate from CBD distillate.

To perform a cooling crystallization, the solute must be sufficiently soluble in the solvent at the start (higher) temperature, and insoluble in the solvent at the end (lower) temperature. The more insoluble at lower temperatures the better, as this improves the theoretical yields over a practical temperature change by driving more of the solute out of solution.

In the case of CBD isolate, the approach is the same. CBD present in CBD distillate, is diluted with hydrocarbon solvent (typically pentane or heptane) and then cooled so that the CBD molecules crystallize as CBD isolate crystals.

What is seeded cooling crystallization?

Below is an illustration of a solubility diagram (Fig. 1) which demonstrates the important relationship between CBD concentration (y axis) and temperature (x axis), and the affect of temperate on CBD phase-behaviour.

General CBD Solubility Curve

Fig 1: Example solubility curve for CBD in a solvent system

There are three zones:

  1. Unsaturated stable zone – below the solubility curve
    The CBD concentration in the solvent system is less than its equilibrium solubility and is below saturation. The temperature is high enough and the concentration is low enough that all the CBD is dissolved. Crystallization process must start in this region. The solubility curve is fixed for a given solvent system.
  2. Labile unstable zone – above the supersolubility curve
    The CBD concentration in the solvent system is much more than its equilibrium solubility. CBD will spontaneously precipitate out of solution as there is sufficient thermodynamic driving force to form a new solid phase. Operation of crystallizers in this region can lead to encrustation when the new solid phase forms on solid surfaces (because the energy barrier is lower). The supersolubility curve is not fixed for a given solvent system, as it is dependent on factors such as cooling rate, mixing intensity, the presence of impurities.
  3. Metastable zone – between the solubility and supersolubility curves
    The CBD concentration in the solvent system is above its equilibrium solubility and is supersaturated, however, it is not sufficiently supersaturated to spontaneously precipitate out of solution (known as spontaneous nucleation). It requires seeds (or another external stimulus) to initiate nucleation. Seeds are crystals of the material that is being crystallized and which have been milled to reduce their particle size. In the case of CBD isolate crystallization, this means milled CBD isolate crystals. The seeds are added as a slurry containing a solid phase of CBD isolate crystal and a liquid phase of a CBD-saturated solvent solution.  During crystallization, the seeds become larger as the CBD comes out of solution.

In a NiTech® continuous crystallizer, the combination of optimal mixing, enhanced heat transfer and the addition of seeds, the operator can keep the CBD concentration in solution inside the metastable zone throughout the crystallization process (see Fig 2.).

CBD optimum seeded crystallization path

Fig 2: Crystallization pathway (superimposed on the solubility curve) when performing seeded, cooling crystallization of CBD isolate in a NiTech® continuous crystallizer

The enhanced control of crystallization pathway in a NiTech® continuous crystallizer results in a high CBD isolate yield (close to the theoretical maximum) and a high-purity product with a uniform crystal size for simpler downstream processing.

What is the difference between precipitation and crystallization?

At NiTech, we are always careful to differentiate between precipitation and crystallization. In chemistry, precipitation is the formation of a solid phase. So, all crystallizations are a sub-set of precipitation processes. It is common to call rapid solid formation precipitation and slow, control formation of a crystalline solid phase crystallization. The difference between the two can cause some confusion for two reasons:

  1. both form a solid phase; and
  2. at first glance, the processes appear to be the same – i.e. removal of a solute from a solvent by causing it to form a solid.

Although the phase of the product is the same (i.e. a solid), the characteristic of the product and the mechanism by which it is formed is different between the two processes.


Precipitation occurs when a solute in a solvent becomes supersaturated to such an extent that it nucleates and spontaneously comes out of solution.

Precipitation is rapid and forms a large quantity of small particles, as rate of formation of new solids greatly exceeds the rate of crystal growth. Also, due to the speed of precipitation, other components become entrapped in the precipitate, resulting in a lower purity material; these can include the solvent as well as other components present in the solvent system at the time.

In the case of CBD, this can mean THC, pesticides, solvent and other cannabinoids becoming entrapped in the CBD crystals, requiring resource-intensive recrystallization operations to achieve the required purity.

In addition to a greater number of impurities, the small particle size results in:

  • the material becoming more compacted and harder to filter effectively as the flow-channels for fluid to drain are narrower;
  • losses during filtration and washing are increased because there is more solid-liquid surface area – negatively impacting on the end-to-end yield;
  • increased time to dry as there is more wet surface area to dry; and
  • caking of solids on the side of the reactor/stirrer.

For these reasons, although quick and easy, precipitation is not an effective or desirable means of isolating a compound from a solution due to poor process performance.


Crystallization occurs when the solute dissolved in a solvent is supersaturated (but not precipitating spontaneously). An external stimulus, e.g. the presence of seeds, is used to initiate nucleation in a controlled manner. Crystallization is the controlled growth of crystals, often from seed crystals. The seed crystals act as de facto catalysts, which lower the energy barrier of crystallization: it is easier for solute to crystallise on an existing crystal surface than to form its own new solid phase, at relatively levels of low supersaturation.

Controlled crystallization in a COBC is gradual and forms large, uniform particles with high purity and yields and makes downstream processing simpler and more effective.

Crystallization is the desired method for isolating a compound from a system.

What happens when crash cooling CBD?

CBD isolate is often produced using crash cooling (this is precipitation). As demonstrated in Fig 3:

  • CBD distillate and a hydrocarbon solvent starts at high temperature in a dissolved state and is quickly cooled.
  • The CBD solution becomes supersaturated and spontaneously forms small CBD isolate crystals.
  • Consequently, the concentration of CBD dissolved decreases.
  • As the mixture continues to cool to its final temperature, both nucleation and growth may occur.
CBD sub-optimum crash-cooling crystallization path

Fig 3: ‘Crash cooling’ crystallization

This method is fast and simple but is not an efficient means of crystallizing CBD isolate as the precipitate forms rapidly and entraps other components. These may include THC, pesticides, solvent, and or any other components that were present in the original distillate. In addition, when CBD isolate is formed via precipitation, the particle size is small and results in the material becoming more compacted and harder to filter effectively, as well as caking on the side of the reactor/stirrer. Due to the small particle size, material is also lost during filtration and washing.

Typically, CBD isolate that has been crash cooled will require at least one recrystallisation (which is at least 2 steps in total) to achieve the desired CBD isolate purity, thus complicating downstream processing and reducing CBD isolate yields and throughputs.

Can you perform seeded, cooling crystallization in batch stirred tanks?

It is possible to attempt seeded, cooling crystallization in batch stirred tanks; like the operation of a NiTech® continuous crystallizer. B/R Instrument’s blog provides a comprehensive explanation of this process: how to crystallize cbd

CBD sub-optimum seeded crystallization path

Fig 4: Seeded, cooling crystallization in large batch stirred tanks (Note: wider arrows are used to illustrate the temperature gradients within the fluid inside a large stirred tank caused by poor mass and heat transfer properties of this equipment)

Batch stirred tanks are severely limited by heat and mass transfer (i.e. the ability to heat or cool their contents and the ability to mix effectively), particularly at larger scales, leading to significant batch to batch variation, reduced CBD isolate yield and purity.

Heat transfer

At larger scales, there is proportionally lower surface area available to transfer heat to the contents of the vessel. This is known as ‘decreasing surface area to volume ratio’. This means that it takes longer to heat or cool the contents of the reactor, making it impossible to respond quickly to dynamic processes, such as crystallization, to keep the vessel’s contents at the correct temperature.

Mass transfer

At larger scales, mixing is less efficient and more energy intensive. Non-uniform mixing causes temperature and concentration gradients to form in the vessel, for example, areas close to the walls of the vessel will be colder than at the centre of the vessel. This leads to areas where, simultaneously within the same vessel, material is both spontaneously precipitating and re-dissolving.

The result is a less severe form of crash cooling, but still far from ideal: CBD isolate precipitates out of solution and other components become entrapped in the CBD isolate crystals. These may include THC, pesticides, solvent, and/or any other components that were present in the original CBD distillate.

In addition, when using batch-based cooling crystallization, the CBD isolate particle size is small and results in the material becoming more compacted, and harder to filter effectively. Due to the small CBD isolate particle size, material is also lost during filtration and washing.


We hope you have found this page useful. We have explained the science behind crystallization and how it applies to CBD isolate production. We also explained how CBD isolate manufacturers can overcome the limitations of established, batch-based crystallization equipment through the application of NiTech’s proprietary continuous crystallizer.

We would be delighted to speak to you if you are interested to learn more about how NiTech® can help your organisation take advantage of the benefits of continuous CBD isolate crystallization.

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