d-Xylose oxetane copolymers as bioderived and tuneable polyesters for amorphous solid dispersions†

Ella F. Clark, Alexandra Howard, Sebastian D. Morales Feliu, James F. McCabe, Jonathan C. Burley, Vincenzo Taresco and Antoine Buchard
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Abstract

The ring-opening copolymerisation of cyclic anhydrides with an oxetane derived from natural monosaccharide D-xylose has been used to synthesise fully biobased water soluble polyesters, which are able to stabilise the amorphous phases of nifedipine and mefenamic acid, enhancing their apparent solubility in water up to 918 and 142% respectively. 2D picolitre-scale inkjet-printing, coupled with polarised optical microscopy (POM) analysis, enabled an initial, high-throughput miniaturised (ng–μg scale) screening of drug formulations. The best formulations were scaled up and analysed by FT-IR spectroscopy and DSC, revealing interactions between the drugs and polymers. Finally, drug dissolution studies demonstrated the effectiveness of the polymers in improving the drugs’ apparent solubility in water. These results showcase the potential of synthetic carbohydrate polymers as excipient for tailored drug formulations.

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d- 木糖氧杂环丁烷共聚物作为生物来源的可调聚酯用于无定形固体分散体†。
利用环状酸酐与源自天然单糖 D-木糖的氧杂环丁烷的开环共聚,合成了完全生物基的水溶性聚酯,这种聚酯能够稳定硝苯地平和甲灭酸的无定形相,使它们在水中的表观溶解度分别提高了 918% 和 142%。二维皮升尺度喷墨打印技术与偏振光学显微镜(POM)分析相结合,实现了药物制剂的初步高通量微型化(纳克微克级)筛选。对最佳配方进行放大,并通过傅立叶变换红外光谱和 DSC 进行分析,揭示药物与聚合物之间的相互作用。最后,药物溶解研究表明,聚合物能有效提高药物在水中的表观溶解度。这些结果展示了合成碳水化合物聚合物作为定制药物制剂辅料的潜力。
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