TY - JOUR
T1 - Molecular Interactions Underlying Dissolution Trends in Cannabidiol-Polymer Amorphous Solid Dispersions
AU - Ugur, Baris E.
AU - Caggiano, Nicholas J.
AU - Monson, Stephanie
AU - Bechtold, Alexander G.
AU - Seo, Yejoon
AU - Prud'homme, Robert Krafft
AU - Priestley, Rodney D.
AU - Webb, Michael A.
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/9/10
Y1 - 2024/9/10
N2 - Cannabidiol (CBD) is viewed as a promising therapeutic agent against a variety of health ailments; however, its efficacy is limited by poor aqueous solubility. Amorphous solid dispersions (ASDs) can enhance the solubility of therapeutics by distributing them throughout a polymer matrix. In consideration of ASD formulations with CBD, we investigate the interactions of CBD with various polymers: poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and poly(methyl methacrylate) (PMMA). Both the experiment and molecular dynamics simulation reveal diverse mixing behavior among the set of polymers. Detailed structural and nanoscale interaction analyses suggest that positive deviations from ideal mixing behavior arise from the formation of stable polymer-CBD hydrogen bonds, whereas negative deviations are associated with disruptions to the polymer-polymer hydrogen bond network. Polymer-water interaction analyses indicate the significance of polymer hydrophobicity that can lead to poor dissolution of CBD. These results have implications for drug dissolution rates based on how CBD and water interact with each polymer. Furthermore, these insights may be used to guide ASD formulations for CBD or other small-molecule therapeutic agents.
AB - Cannabidiol (CBD) is viewed as a promising therapeutic agent against a variety of health ailments; however, its efficacy is limited by poor aqueous solubility. Amorphous solid dispersions (ASDs) can enhance the solubility of therapeutics by distributing them throughout a polymer matrix. In consideration of ASD formulations with CBD, we investigate the interactions of CBD with various polymers: poly(vinylpyrrolidone) (PVP), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), and poly(methyl methacrylate) (PMMA). Both the experiment and molecular dynamics simulation reveal diverse mixing behavior among the set of polymers. Detailed structural and nanoscale interaction analyses suggest that positive deviations from ideal mixing behavior arise from the formation of stable polymer-CBD hydrogen bonds, whereas negative deviations are associated with disruptions to the polymer-polymer hydrogen bond network. Polymer-water interaction analyses indicate the significance of polymer hydrophobicity that can lead to poor dissolution of CBD. These results have implications for drug dissolution rates based on how CBD and water interact with each polymer. Furthermore, these insights may be used to guide ASD formulations for CBD or other small-molecule therapeutic agents.
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U2 - 10.1021/acs.macromol.4c01579
DO - 10.1021/acs.macromol.4c01579
M3 - Article
AN - SCOPUS:85201698540
SN - 0024-9297
VL - 57
SP - 8287
EP - 8297
JO - Macromolecules
JF - Macromolecules
IS - 17
ER -