College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.
Jiangxi Province Integrative Hospital of Chinese Medicine and Western Medicine, Nanchang, China.
AAPS PharmSciTech. 2024 Sep 7;25(7):210. doi: 10.1208/s12249-024-02926-3.
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.
托塞米是一种长效吡啶磺酰脲类利尿剂。盐酸托塞米目前应用广泛，但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。在这里，我们报道了托塞米的马来酸盐和邻苯二甲酸盐，其中有机酸失去质子转移到托塞米的吡啶上，托塞米通过 N-H⋯O 氢键与有机酸相互作用形成盐晶体。令人惊讶的是，马来酸盐在表观溶解度上表现出明显的“弹簧”模式，而邻苯二甲酸盐则具有“弹簧-降落伞”效应。两种晶体盐的溶解度都保持在较高水平，高于没有下降的托塞米。晶体盐的“弹簧-降落伞”效应促进了托塞米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。
