School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Carbohydr Polym. 2020 Feb 15;230:115601. doi: 10.1016/j.carbpol.2019.115601. Epub 2019 Nov 11.
The objective of this study is to investigate the influence of drug-alginate miscibility on maintaining drug supersaturation. Using lovastatin, indomethacin, itraconazole as model drugs, drug-alginate miscibility was estimated by Hansen solubility parameters. The mechanism of drug-alginate miscibility on maintaining drug supersaturation was elucidated by microscopy, molecular mobility (T), FTIR and X-ray crystallography. The influence of alginate properties on maintaining drug supersaturation was also examined. It was demonstrated that the capacity of alginate to maintain drug supersaturation was dependent on alginate-drug miscibility. Further mechanistic study revealed that alginate interacts with drugs via hydrogen bonding at different extent based on varied drug-alginate miscibility. Alginate could suppress drug molecular mobility and corresponding crystal growth inhibition. The properties of alginate also play an important role in maintaining drug supersaturation. In conclusion, alginate could be used as a potential crystal growth inhibitor, and the crystal growth inhibition effect depends on drug-alginate miscibility and alginate properties.
本研究旨在探讨药物-海藻酸钠混溶性对维持药物过饱和度的影响。以洛伐他汀、吲哚美辛、伊曲康唑为模型药物，通过 Hansen 溶解度参数估算药物-海藻酸钠混溶性。通过显微镜、分子迁移率（T）、傅里叶变换红外光谱（FTIR）和 X 射线晶体学阐明了药物-海藻酸钠混溶性维持药物过饱和度的机制。还考察了海藻酸钠性质对维持药物过饱和度的影响。结果表明，海藻酸钠维持药物过饱和度的能力取决于海藻酸钠-药物的混溶性。进一步的机制研究表明，海藻酸钠通过氢键与药物相互作用，其相互作用程度取决于不同的药物-海藻酸钠混溶性。海藻酸钠可抑制药物分子迁移率，从而抑制相应的晶体生长。海藻酸钠的性质对维持药物过饱和度也起着重要作用。综上所述，海藻酸钠可用作潜在的晶体生长抑制剂，其抑制晶体生长的效果取决于药物-海藻酸钠的混溶性和海藻酸钠的性质。
