Crystal Structural Analysis of DL-Mandelate Salt of Carvedilol and Its Correlation with Physicochemical Properties

A 1:1 salt of carvedilol (CVD), an anti-hypertensive drug, with DL-mandelic acid (DL-MA) was crystallized from ethanol and the structure was characterized by X-ray single-crystal diffraction, revealing salt formation by transfer of an acidic proton from the COOH group of MA to the aliphatic (acyclic) secondary amino NH group of CVD. The crystal structure is triclinic, with a P-1 space group and unit cell parameters a = 9.8416(5) angstrom, b = 11.4689(5) angstrom, c = 14.0746(7) angstrom, alpha = 108.595(8), beta = 95.182(7), gamma = 107.323(8), V = 1406.95(15) angstrom(3), and Z = 2. The asymmetric unit contained one protonated CVD and one MA anion, linked via an N+-H center dot center dot center dot O over bar strong hydrogen bond and a ratio of 1:1. As previously reported, the thermal, spectroscopic, and powder X-ray diffraction properties of the salt of CVD with DL-MA (CVD_DL-MA) differed from CVD alone. The intrinsic dissolution rate of CVD_DL-MA was about 10.7 times faster than CVD alone in a pH 6.8 buffer.