Triamterene-furosemide salt: structural aspects and physicochemical evaluation

Furosemide (Fur) is a BCS class IV diuretic drug with low bioavailability due to its poor solubility and poor membrane permeability. Triamterene (Tri) is a potassium-sparing diuretic with low bioavailability due to its poor solubility. Here, a novel drug-drug salt composed of Tri and Fur was successfully synthesized. Tri-Fur was comprehensively characterized with single-crystal X-ray and powder X-ray diffraction techniques, thermogravimetric analysis, differential scanning calorimetry and dynamic vapor sorption. The apparent equilibrium solubility (in pH 2.0 buffer) of Tri-Fur is improved compared with Fur and a physical mixture of Tri with equimolar Fur by 15.3-fold and 12.2-fold enhancements, respectively. Its intrinsic dissolution rate (in pH 2.0 buffer) is also higher than for a Fur component with an enhancement of 9.5-fold. This study provides a valuable insight into the formation of dual pharmaceutical salts and demonstrates that Tri-Fur can be a potential alternative formulation.