Structural characterization of three crystalline modifications of telmisartan by single crystal and high-resolution X-ray powder diffraction

Three crystalline modifications (A, B, and C) of 4\'-[[2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)benzi midazol-1-yl]methyl]biphenyl-2-carboxylic acid (INN name, telmisartan) have been detected and their crystal structures have been determined by single-crystal X-ray diffraction (pseudopolymorph C)and the method of simulated annealing from high-resolution X-ray powder diffraction data (polymorphs A and B). The compound is of interest because of its use as an angiotensin II receptor antagonist. Polymorph A crystallizes in space group P2(I)/c, Z = 4, with unit cell parameters a = 18.7798(3), b = 18.1043(2), and c = 8.00578(7) Å, β = 97.066(1)°, and V = 2701.31 Å3. Polymorph B crystallizes in space group P2(I)/a, Z = 4, with unit cell parameters a = 16.0646(5), b = 13.0909(3), and c = 13.3231(3) Å, β = 99.402(1)°, and V = 2764.2(1) Å3. The solvated form C crystallizes in space group C2/c, Z = 8, with unit cell parameters a = 30.990(5), b = 13.130(3), and c = 16.381(3) Å, β = 95.02(2)°, and V = 6639(2) Å3. For the structure solutions of polymorphs A and B, 13 degrees of freedom (3 translational, 3 orientational, 7 torsion angles) were determined in ~2 h of computer time, demonstrating that the crystal packing and the molecular conformation of medium-sized (MW ≃ 500) pharmaceutical compounds can now be solved quickly and routinely from high-resolution X-ray powder diffraction data. (C) 2000 Wiley-Liss, Inc.