(742d) Nanoencapsulation of Cannabidiol Via Flash Nanoprecipitation with Naturally Derived Polymer Stabilizers

Hydrophobic small molecule drugs and nutraceuticals present obstacles for oral administration. Their poor aqueous solubility and large oil/water partition coefficients often result in poor in vivo bioavailability. One approach to address this issue is the encapsulation and stabilization of amorphous hydrophobic actives in nanoparticles, where the greater surface area afforded by the nanoparticles, along with the free energy advantage of the amorphous drug, may enhance the release of the drug. The encapsulation of therapeutics which exist primarily as liquid oils poses additional challenges to the formation, solidification, and characterization of these nanoparticles.

Here, we investigate the encapsulation of cannabidiol (CBD) as a model drug. CBD in its amorphous state has a low glass transition temperature and at ambient temperature exists as a nonaqueous liquid. We show that amorphous CBD can be effectively encapsulated into nanoparticles with low polydispersity and high drug loading via Flash NanoPrecipitation, a scalable self-assembly process. Two naturally derived polymers, HPMCAS and lecithin, are employed as amphiphilic particle stabilizers. The resulting nanoparticle suspensions are size stable over time and are thus suitable for further downstream processing. Lastly, we show that the nanoparticle formulation can enhance the release rate of CBD in vitro, and the release rate may be tuned by varying the particle properties.