TY - JOUR
T1 - Polymorphism in Sulfadimidine/4-Aminosalicylic Acid Cocrystals: Solid-State Characterization and Physicochemical Properties
AU - Grossjohan, Christine
AU - Serrano, Delores R.
AU - Paluch, Krzysztof J.
AU - O'Connell, Peter
AU - Vella-Zarb, Liana
AU - Manesiotis, Panagiotis
AU - McCabe, Thomas
AU - Tajber, Lidia
AU - Corrigan, Owen I.
AU - Healy, Anne Marie
PY - 2015/4
Y1 - 2015/4
N2 - 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.
AB - 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.
U2 - 10.1002/jps.24345
DO - 10.1002/jps.24345
M3 - Article
SN - 0022-3549
VL - 104
SP - 1385
EP - 1398
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 4
ER -