Puerarin-Na Chelate Hydrate Simultaneously Improves Dissolution and Mechanical Behavior,Molecular Pharmaceutics

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Puerarin-Na Chelate Hydrate Simultaneously Improves Dissolution and Mechanical Behavior
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-06-18 , DOI: 10.1021/acs.molpharmaceut.1c00005
Hui Chen ₁ , Zunting Pang ₂ , Qiyang Qiao ₁ , Yanming Xia ₂ , Yuanfeng Wei ₂ , Yuan Gao ₂ , Jianjun Zhang ₁ , Shuai Qian ₂

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Puerarin monohydrate (PUEM), as the commercial solid form of the natural anti-hypertension drug puerarin (PUE), has low solubility, poor flowability, and mechanical properties. In this study, a novel solid form as PUE-Na chelate hydrate was prepared by a reactive crystallization method. Crystal structure analysis demonstrated that PUE-Na contains PUE^–, Na⁺, and water in a molar ratio of 1:1:7. It crystallizes in the monoclinic space group P2₁, and Na⁺ is linked with PUE^– and four water molecules through Na⁺ ← O coordination bonds. Another three crystal water molecules occupy channels along the crystallographic b-axis. Observing along the b-axis, the crystal structure features a distinct tubular helix and a DNA-like twisted helix. The complexation between Na⁺ and PUE^– in aqueous solution was confirmed by the Na⁺ selective electrode, indicating that PUE-Na chelate hydrate belongs to a type of chelate rather than organic metal salt. Compared with PUEM, PUE-Na exhibited a superior dissolution rate (i.e., ∼38-fold increase in water) owing to its lower solvation free energy and clear-enriched exposed polar groups. Moreover, PUE-Na enhanced the tabletability and flowability of PUEM, attributing to its better elastoplastic deformation and lower-friction crystal habit. The unique PUE-Na chelate hydrate with significantly enhanced pharmaceutical properties is a very promising candidate for future product development of PUE.

中文翻译：

葛根素钠螯合物同时改善溶解和机械行为

葛根素一水合物（PUEM）作为天然抗高血压药物葛根素（PUE）的商业固体形式，溶解度低、流动性差、力学性能差。在本研究中，通过反应结晶法制备了一种新型固体形式的 PUE-Na 螯合物水合物。晶体结构分析表明，PUE-Na含有摩尔比为1:1:7的PUE ^-、Na ⁺和水。它在单斜晶系空间群P 2 _{1 中}结晶，Na ⁺与PUE ^-和四个水分子通过Na ⁺ ← O 配位键连接。另外三个结晶水分子占据沿结晶b 的通道-轴。沿b轴观察，晶体结构具有明显的管状螺旋和类似 DNA 的扭曲螺旋。的Na之间的络合⁺和PUE ^-在水溶液中被确认的Na ⁺选择性电极，表明PUE-Na螯合物水合物属于螯合物，而不是有机金属盐。与 PUEM 相比，PUE-Na 表现出优异的溶解速率（即在水中增加 38 倍），这是由于其较低的溶剂化自由能和富含透明的暴露极性基团。此外，PUE-Na 增强了 PUEM 的可压片性和流动性，这归因于其更好的弹塑性变形和低摩擦晶体习性。独特的 PUE-Na 螯合物水合物具有显着增强的药学特性，是未来 PUE 产品开发的非常有希望的候选者。

更新日期：2021-07-05

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