Torsemide Crystalline Salts with a Significant Spring-Parachute Effect

Area of Science:

• Pharmaceutical Science
• Materials Science
• Medicinal Chemistry

Background:

• Torsemide is a long-acting pyridine sulfonylurea diuretic.
• Improving torsemide solubility is crucial for enhanced bioavailability.
• Few organic acid salts of torsemide have been reported.

Purpose of the Study:

• To investigate the cocrystallization of torsemide with organic acids.
• To characterize novel torsemide maleate and phthalate salts.
• To evaluate the impact of these salts on torsemide solubility and dissolution.

Main Methods:

• Cocrystallization of torsemide with maleic acid and phthalic acid.
• Salt formation via proton transfer to the pyridine nitrogen of torsemide.
• Analysis of crystal structures and hydrogen bonding (N+–H⋯O−).
• Solubility studies to observe dissolution patterns ('spring' and 'spring-parachute' effects).

Main Results:

• Torsemide maleate and phthalate salts were successfully synthesized.
• Proton transfer from the organic acid to torsemide's pyridine ring was confirmed.
• Both salts exhibited enhanced solubility compared to pure torsemide.
• Maleate showed a 'spring' solubility profile, while phthalate displayed a 'spring-parachute' effect.
• The crystalline salts maintained higher solubility without significant loss.

Conclusions:

• Cocrystallization with organic acids is an effective strategy to improve torsemide solubility.
• Torsemide maleate and phthalate salts offer improved dissolution profiles.
• The observed solubility effects ('spring' and 'spring-parachute') can enhance torsemide concentration and bioavailability.