| Abstract |
Sulfadimethoxine (SDM) cocrystal formation was screened using coformers with cyclic amines, amide, carboxylic acid, and sulfonamide based moieties. Eight new multicomponent crystal forms were obtained by solution crystallization and liquid-assisted grinding techniques, showing a preference for the amine derivatives. Cocrystals were obtained with isonicotinamide (SDM:ISO) and 4,4 -bipyridine (SDM:BI-P:ACE; SDM:BIP:H2O), and molecular salts were synthesized with piperazine (SDM:PIP), 4,4 -trirnethylenedipiperidine (SDM:TRI), and 1,4-diazabicyclo[2.2.2]octane (two anhydrous polymorphic forms (SDM:DABCO) and one hydrate (SDM:D.ABCO:H2O)). The new forms were fully characterized by X-ray diffraction. Structural characterization shows the disruption of the typical R-2(2)(8) sulfonamide synthon, while the supramolecular arrangement is achieved through several new synthons. In cocrystals, the amide nitrogen N-sulfonamide behaves as the best donor and bonds to the O-acetamide of ISO, while with BIP the interaction is established with the N-BIP, atom. In salts, charge assisted hydrogen bonds are established, predominantly with the amide nitrogen, the best acceptor, or the sulfonyl 0 atom, but there is a strong competition with the N atom of the pyrazine ring (N-pyrazine). Thermal behavior and physicochemical properties were assessed by thermogravimetric analysis, differential scanning calorimetry, variable temperature powder X-ray diffraction, and hot-stage microscopy techniques. As expected, the molecular salts reveal higher solubility in water than the cocrystals, an important aspect for the improvement of SDM performance. |
