Stability study and structural insights into cannabidiol cocrystals†

Cannabidiol (CBD) is a non-psychoactive compound derived from cannabis and has attracted considerable attention due to its potential therapeutic benefits. It is increasingly used in various health-related products, including dietary supplements, because of its positive effects on pain relief, antioxidative properties, and protection against cell damage. Despite its promising applications, CBD faces significant challenges for oral administration, primarily due to its low solubility, low melting point (67 °C), and poor stability. In this work, we used various methods for CBD cocrystal preparation to improve properties of CBD. We succeeded in preparing five cocrystals, which were fully characterized using several analytical tools, such as X-ray powder diffraction, differential scanning calorimetry, and nuclear magnetic resonance. Notably, the cocrystals increased their melting points compared to pure CBD. Furthermore, the intrinsic dissolution rate was measured for pure CBD and the multicomponent forms to describe the rate of release of CBD from the cocrystal. Finally, the crystal structures of three cocrystals were used to interpret the stability and degradation behaviour of the CBD cocrystals under accelerated conditions. Remarkably, the cocrystals CBD–4,4′-bipyridine and CBD–L-proline remained stable and unaffected for a longer period under stress conditions compared to the pure CBD. This study provides valuable insight into the stability behaviour of the cocrystals under various conditions.