Molecular Interactions Underlying Dissolution Trends in Cannabidiol-Polymer Amorphous Solid Dispersions,Macromolecules

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Molecular Interactions Underlying Dissolution Trends in Cannabidiol-Polymer Amorphous Solid Dispersions
Macromolecules ( IF 5.1 ) Pub Date : 2024-08-20 , DOI: 10.1021/acs.macromol.4c01579
Baris E. Ugur ₁ , Nicholas J. Caggiano ₁ , Stephanie Monson ₁ , Alexander G. Bechtold ₁ , Yejoon Seo ₁ , Robert K. Prud’homme ₁ , Rodney D. Priestley ₁ , Michael A. Webb ₁

Affiliation

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.

中文翻译：

大麻二酚-聚合物无定形固体分散体溶解趋势背后的分子相互作用

大麻二酚 (CBD) 被视为一种有前景的治疗多种健康疾病的药物；然而，其功效因水溶性差而受到限制。无定形固体分散体（ASD）可以通过将治疗药物分布在整个聚合物基质中来增强治疗药物的溶解度。考虑到含有 CBD 的 ASD 配方，我们研究了 CBD 与各种聚合物的相互作用：聚（乙烯基吡咯烷酮）（PVP）、聚（乙烯基吡咯烷酮）/乙酸乙烯酯（PVP/VA）共聚物、邻苯二甲酸羟丙甲基纤维素（HPMCP）、乙酸羟丙甲基纤维素琥珀酸酯 (HPMCAS) 和聚甲基丙烯酸甲酯 (PMMA)。实验和分子动力学模拟都揭示了聚合物组之间不同的混合行为。详细的结构和纳米级相互作用分析表明，与理想混合行为的正偏差是由于稳定的聚合物-CBD氢键的形成而产生的，而负偏差则与聚合物-聚合物氢键网络的破坏有关。聚合物-水相互作用分析表明聚合物疏水性的重要性可能导致 CBD 溶解不良。根据 CBD 和水与每种聚合物的相互作用，这些结果对药物溶出率有影响。此外，这些见解可用于指导 CBD 或其他小分子治疗剂的 ASD 配方。

更新日期：2024-08-20

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