具有显著弹簧降落伞效应的托塞米结晶盐。

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-09-07 DOI:10.1208/s12249-024-02926-3

Xuezhen Deng, Weimin Shi, Kun Qian, Jie Yang, Siyu Yuan, Hong Li

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引用次数: 0

摘要

托西米是一种长效吡啶磺酰脲类利尿剂。盐酸托昔米目前已被广泛使用，只有少数有机酸盐被报道。与有机酸共结晶是提高其溶解度的有效方法。本文报道了托瑞米特的马来酸盐和邻苯二甲酸盐，其中有机酸失去了一个质子转移到托瑞米特的吡啶上，托瑞米特通过N+ - H⋯O-氢键与有机酸相互作用形成盐晶体。令人惊讶的是，马来酸盐的表观溶解度呈现出明显的 "弹簧 "模式，而邻苯二甲酸盐则呈现出 "弹簧-降落伞 "效应。这两种结晶盐都保持了比托昔米特更高的溶解度而没有下降。结晶盐的 "弹簧降落伞 "效应促进了托瑞米特的快速溶解，并保持了较高的浓度，从而提高了其生物利用度。

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Torsemide Crystalline Salts with a Significant Spring-Parachute Effect

Torsemide is a long acting pyridine sulfonylurea diuretic. Torsemide hydrochloride is widely used now, there are only a few organic acid salts reported. Cocrystallization with organic acids is an effective way to improve its solubility. Here, we reported maleate and phthalate of torsemide, in which the organic acid lost a proton transferring to the pyridine of torsemide, and torsemide interacted with organic acid through N⁺ − H⋯O⁻ hydrogen bond to form salts crystal. Surprisingly, maleate showed a clear "spring" pattern in apparent solubility, whereas phthalate had a "spring-parachute" effect. Both crystalline salts kept a higher solubility than torsemide without falling. The "spring-parachute" effect of crystalline salts promoted rapid dissolution of torsemide and kept a high concentration, thereby increasing its bioavailability.