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 P2I/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 P2I/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. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1465–1479, 2000