A Red Zwitterionic Co-Crystal of Acetaminophen and 2,4-Pyridinedicarboxylic Acid

ABSTRACTWe report on a co-crystal of acetaminophen (APAP) and 2,4-pyridinedicarboxylic acid (PDA). The co-crystal was discovered by screening using the solution-mediated phase transformation (SMPT) technique. Despite the bulk solids of each component being white in color, the new co-crystal phase exhibited a red color. The new phase was analyzed using single-crystal X-ray diffraction and identified as (APAP) (PDA) (1). Structural analysis revealed PDA to exist in a hitherto unreported zwitterionic form in the co-crystal. A structural analysis of pure PDA revealed the presence of the zwitterion form in (PDA)(H2O) (2), as well. The components of 1 self-assemble as a three-dimensional (3D) hydrogen-bonded network with a pronounced 2D structure. The origin of the red color was investigated using density functional theory calculations, which demonstrate a decreasing π–π* separation involving the components of the solid. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3676–3683, 2010