Abstract：
The chemical structure of excipients molecularly mixed in an amorphous solid dispersion (ASD) has a significant impact on properties of the ASD including dissolution behavior, physical stability, and bioavailability. Polymers used in ASDs require a balance between hydrophobic and hydrophilic functionalities to ensure rapid dissolution of the amorphous dispersion as well as sustained supersaturation of the drug in solution. This work demonstrates the use of postpolymerization functionalization of poly(vinylpyridine) excipients to elucidate the impact of polymer properties on the dissolution behavior of amorphous dispersions containing posaconazole. It was found that N-oxidation of pyridine functionalities increased the solubility of poly(vinylpyridine) derivatives in neutral aqueous conditions and allowed for nanoparticle formation which supplied posaconazole into solution at concentrations exceeding those achieved by more conventional excipients such as hydroxypropyl methylcellulose acetate succinate (HPMCAS) or Eudragit E PO. By leveraging these functional modifications of the parent poly(vinylpyridine) excipient to increase polymer hydrophilicity and minimize the effect of polymer on pH, a new polymeric excipient was optimized for rapid dissolution and supersaturation maintenance for a model compound.
摘要：
在无定形固体分散体(ASD)中分子混合的赋形剂的化学结构对ASD的性质(包括溶出行为)具有显著影响。物理稳定性,和生物利用度。用于ASD的聚合物需要疏水性和亲水性官能团之间的平衡,以确保无定形分散体的快速溶解以及药物在溶液中的持续过饱和。这项工作证明了使用聚（乙烯基吡啶）赋形剂的后聚合官能化来阐明聚合物性能对包含泊沙康唑的无定形分散体的溶解行为的影响。发现吡啶官能团的N-氧化增加了聚（乙烯基吡啶）衍生物在中性水性条件下的溶解度，并允许形成纳米颗粒，该纳米颗粒以超过更常规的赋形剂如醋酸羟丙基甲基纤维素琥珀酸酯（HPMCAS）或EudragitEPO所达到的浓度提供泊沙康唑到溶液中。通过利用母体聚（乙烯基吡啶）赋形剂的这些功能修饰来增加聚合物的亲水性并最小化聚合物对pH的影响，针对模型化合物的快速溶解和过饱和维持,优化了一种新的聚合物赋形剂.
