Design and Bottom-up Production of an Aerosolizable Cannabidiol Nanosuspension

Cannabidiol (CBD), a small nonpsychoactive molecule derived from <i>Cannabis sativa</i>, exerts a variety of therapeutic actions, such as anti-inflammatory, antioxidant, and antibacterial. Epidiolex is the only FDA-approved medicine containing pure CBD as an oral solution for seizure-controlling therapy. Nevertheless, the oral bioavailability of CBD is challenging due to its physical-chemical properties such as low solubility in water and high first-pass metabolism. By contrast, inhaled CBD has shown faster absorption and higher plasma concentration. Nanosuspensions represent an optimal strategy to obtain an effective aerosolizable formulation of poorly soluble drugs. In this study, a CBD nanosuspension was produced using a bottom-up technique, namely, a solvent/antisolvent nanoprecipitation. The obtained system was thoroughly characterized in terms of dimensions and ζ potential, nanocrystal morphology, and solid-state properties. The formulation was composed of homogeneously dispersed nanocrystals of approximately 88 nm, with a faster dissolution profile compared with the raw drug and the coarse suspension. The nebulization tests carried out using a Next Generation Impactor (NGI, Apparatus E Ph. Eu) highlighted optimal aerodynamic properties with high values of fine particle fraction and MMAD < 5 μm. Finally, the safety of the nanomedicine was assessed on human pulmonary cells demonstrating excellent biocompatibility.