Structural studies of crystalline forms of triamterene with carboxylic acid, GRAS and API molecules

Abstract

Pharmaceutical salt solvates (dimethyl sulfoxide, DMSO) of the drug triamterene with the coformers acetic, succinic, adipic, pimelic, azelaic and nicotinic acid and ibuprofen are prepared by liquid-assisted grinding and solvent-evaporative crystallization. The modified ΔpKa rule as proposed by Cruz-Cabeza [(2012). CrystEngComm, 14, 6362–6365] is in close agreement with the results of this study. All adducts were characterized by X-ray diffraction and thermal analytical techniques, including single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermal gravimetric analysis. Hydrogen-bonded motifs combined to form a variety of extended tapes and sheets. Analysis of the crystal structures showed that all adducts existed as salt solvates and contained the aminopyridinium–carboxylate heterodimer, except for the solvate containing triamterene, ibuprofen and DMSO, as a result of the presence of a strong and stable hemitriamterenium duplex. A search of the Cambridge Structural Database (CSD 5.36, Version 1.18) to determine the frequency of occurrence of the putative supramolecular synthons found in this study showed good agreement with previous work.

Keywords

• triamterene
• pKa analysis
• crystal engineering
• liquid-assisted grinding
• pharmaceutical salt solvates
• hydrogen bonding
• motif analysis
• stable duplex structures