Crystallization of CBD

Over the last several years, cannabidiol (CBD) from hemp experienced an upsurge in acceptance by the general population. The change in regulations around CBD–rich hemp, the FDA approval of Epidiolex (an epilepsy drug containing CBD), and the non-intoxicating nature of CBD have fueled the increase in cultivation, production, and demand. CBD is only one of the many cannabinoids produced by hemp and cannabis plants. Due to regulations on limits of THC contamination, isolation of purer forms of CBD is one of the most important steps of the production process. The isolation of pure CBD from less pure mixtures is commonly accomplished by recrystallization.

Understanding the crystallization process is critical to successfully scale up CBD isolation. Since the cannabis and CBD–hemp industries are relatively young, very little research has been performed optimizing CBD recrystallization. Poor understanding of the process tends to cause inconsistencies in yield, particle size of crystals, and purity of CBD. In this regard, most cannabinoid isolation efforts do not leverage process analytical technologies (PAT) to provide a more thorough understanding of crystallization mechanics.

Therefore, it is not surprising that current recrystallization methods are highly inefficient. In addition to decreased yield and purity of CBD, such inefficient recrystallization methods also affect downstream processing such as filtration times, drying, milling, and formulating. Fortunately, these issues can be mitigated by a more thorough understanding of the solubility of the system.

There are a few basic concepts that need to be understood for efficient CBD recrystallization:

• CBD solubility represents the amount of CBD fully dissolved in a given amount of solvent at a specific temperature.
• Supersaturation is when the solution contains more CBD than could normally be dissolved by the solvent at a particular temperature.
• Nucleation is the first step of crystallization when the first CBD crystals form from the solution.
• The Metastable Zone Boundary represents the “cloud point” for a given CBD concentration or where the system spontaneously nucleates to form crystals.
• Metastable Zone Width (MSZW) is the ‘area’ between the solubility and metastable zone boundary.

Download the full Crystallization of CBD white paper and learn more about the importance of CBD Metastable Zone Width Determination as well as experimental set-up, methodology, and results.