title: Polymorphism in sulfadimidine/4-aminosalicylic acid cocrystals: solid-state characterization and physicochemical properties.
abstract: Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid-state characterization of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high-resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared with a physical equimolar mixture and pure SD. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1385-1398, 2015.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Christine
authors.initials: C
authors.lastname: Grossjohann
authors.forename: Dolores R
authors.initials: DR
authors.lastname: Serrano
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Paluch
authors.forename: Peter
authors.initials: P
authors.lastname: O'Connell
authors.forename: Liana
authors.initials: L
authors.lastname: Vella-Zarb
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Manesiotis
authors.forename: Thomas
authors.initials: T
authors.lastname: Mccabe
authors.forename: Lidia
authors.initials: L
authors.lastname: Tajber
authors.forename: Owen I
authors.initials: OI
authors.lastname: Corrigan
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
mesh_terms: D000096:Acetone / Q000737:chemistry; D010131:Aminosalicylic Acid / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004338:Drug Combinations; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013418:Sulfamethazine / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D012997:Solvents; D000096:Acetone; D000431:Ethanol; D013418:Sulfamethazine; D010131:Aminosalicylic Acid
keywords: 4-aminosalicylic acid; cocrystals; dissolution; milling; polymorphism; solid state; solubility; spray drying; sulfadimidine