Molecular Interactions\nUnderlying Dissolution Trends\nin Cannabidiol-Polymer Amorphous Solid Dispersions

Cannabidiol (CBD) is viewed as a promising therapeutic\nagent against\na variety of health ailments; however, its efficacy is limited by\npoor aqueous solubility. Amorphous solid dispersions (ASDs) can enhance\nthe solubility of therapeutics by distributing them throughout a polymer\nmatrix. In consideration of ASD formulations with CBD, we investigate\nthe interactions of CBD with various polymers: poly(vinylpyrrolidone)\n(PVP), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) copolymer, hydroxypropyl\nmethylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate\nsuccinate (HPMCAS), and poly(methyl methacrylate) (PMMA). Both the\nexperiment and molecular dynamics simulation reveal diverse mixing\nbehavior among the set of polymers. Detailed structural and nanoscale\ninteraction analyses suggest that positive deviations from ideal mixing\nbehavior arise from the formation of stable polymer–CBD hydrogen\nbonds, whereas negative deviations are associated with disruptions\nto the polymer–polymer hydrogen bond network. Polymer–water\ninteraction analyses indicate the significance of polymer hydrophobicity\nthat can lead to poor dissolution of CBD. These results have implications\nfor drug dissolution rates based on how CBD and water interact with\neach polymer. Furthermore, these insights may be used to guide ASD\nformulations for CBD or other small-molecule therapeutic agents.