The Solubility and Stability Profiles of Cannabidiol

Quality assurance and the physical properties of cannabinoids

In view of the increasing use of cannabidiol for different medical and recreational uses, there is a need for standard product characterization for safety concerns and product quality assessment inquiries. As with other naturally occurring products, a pure sample of cannabidiol has specific values defining physical properties like density, molecular weight, melting point, stability, refractive index, and solubility in different solvents. To meet regulatory requirements, a sample of cannabidiol must conform with the standard values defining these physical properties. 

Significant variations in these values suggest the presence of impurities in the CBD sample. Impurities can be pesticides, mycotoxins, terpenes, and chemical contaminants of industrial extraction processes. Testing procedures used for quality assurance assessment of a CBD sample generally involve the use of specialized instrumentations and predesigned analytical procedures that are sensitive and easily reproducible. The analytical tests are primarily aimed at determining the Maximum Contaminant Level (MCL) of a CBD sample and ascertaining if the value conforms with acceptable standards. 

The stability profile of CBD explains how the integrity of a CBD sample is maintained in a different environment. Stability studies are important for storage processes and also play an important role in dosage form presentation. At different storage conditions and form—capsules, oil, tinctures, and injectables—stability of CBD differs. The solubility profile of CBD, on the other hand, explains the nature of this naturally occurring compound in different solvents. “Medibles”—marijuana edibles packaged as baked goods and candies—are popular in regions where marijuana use is regulated, an idea of CBD solubility and stability can enhance processing, optimal use, and storage in these regions.  

Stability profile of CBD

CBD is a naturally occurring cannabinoid and, as such expected to show different stability rates in both natural and synthetic mediums. External factors like light and temperature are also expected to affect the rate of stability of CBD on prolonged storage. Currently, only a few research information is available on the stability of CBD as a result of its strict use regulations. One of the most prominent papers examining the stability of CBD and its preparations on storage was published by the Journal of Pharmacy of Pharmacology. 

As reported, cannabinoids respond significantly to light sources and common industrial solvents. CBD is significantly less stable in Chloroform, even in the dark. Using chloroform of a spectrograde quality, the investigators reported rapid decomposition of CBD in both artificial and natural light. Ethanolic extract of this compound was found to be relatively stable in the dark with a fair rate of decomposition in the light. Temperature studies also revealed that at a temperature below 20˚, decomposition was not marked in CBD samples; however, at 37 and 50˚, significant loss of compound was recorded. Result documentation also suggested that the rate of decomposition on exposure to oxygen is minimal and can also depend on the purity of the compound. 

Improving the stability of a CBD sample

Cannabidiol prepared for medical purposes are expected to be stored for a prolonged period of time until needed. Decomposition can reduce product quality and form trace quantities of breakdown products that can be toxic to the biological system. Storage condition modifications are the recommended method of improving the stability of CBD samples. CBD products can be stored in amber-colored containers and stored away from strong light. Alternatively, CBD isolates can be stored in a solvent or solvent mixture that confers stability on the sample. Isolates can be reconstituted with a suitable solvent when needed and used immediately. 

Solubility profile of CBD

Generally, cannabinoids are negligibly soluble in water but are highly soluble in lipids and accumulate abundantly in the body’s fatty tissues. Cannabinoid samples acquired from different production outfits are normally packaged with solubility reports as determined at specified laboratory conditions using different solvents. CBD samples are mostly delivered as a solution in methanol. For specific use in other solvents, the methanol can be evaporated under a gentle stream of nitrogen. Different research inquiries have examined the solubility of CBD in ethanol, methanol, DMSO, and dimethylformamide. The solubility of CBD in these solvents was suggested to be approximately 35, 30, 60, and 50mg/ml, respectively. 

Aqueous buffers have been increasingly used in the extracting and preparation of products derived from natural sources. However, cannabidiol has been proven to be sparingly soluble in aqueous buffers. Should there be a need to use the CBD sample in aqueous buffers, it is advisable to first dilute the CBD sample in DMSO before proceeding with dilution in an aqueous buffer of choice. Some experts have also suggested the use of solvent mixtures for optimal dilution of a CBD sample, specifically recommending 1:3 mixtures of DMSO and PBS. In this mixture, CBD has a solubility of 250ug/ml. 

Improving the solubility of a CBD sample

Cannabinoid samples used are not only expected to be presented in pure isolate form with minimal contamination, but also presented in a highly soluble form. Solubility is particularly improved in orally administered CBD forms. To improve the absorption and solubility of CBD samples, the delivery mechanism is modified. The common form of modified delivery mechanism exploited in the use of CBD is the colloids—a combination of nanotechnology and encapsulation techniques. To form a colloid, the CBD particles are reduced and packed in a bubble with a hydrophilic exterior and a hydrophobic interior. The colloid network produced is a fine emulsion made of nano-sized bubbles that are evenly dispersed in the body system.   

REFERENCES

• https://pubmed.ncbi.nlm.nih.gov/6643/
• https://researchgate.net/figure/cannabidiol-CBD-stability-experiments-under-various-storage-conditions_tbl1_335077348/amp
• https://discovercbd.com/blogs/cbd-news-soluble-cbd-and-the-benefits-explained
• https://pubchem.ncbi.nlm.nih.gov/compound/Cannabidiol
• https://www.drugbank.ca/drugs/DB09061