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Polymorphism in sulfadimidine/4- aminosalicylic acid cocrystals: solid-state characterization and physicochemical properties
Grossjohann, C. Serrano, D.R. Paluch, Krzysztof J. O'Connell, P. Vella-Zarb, L. Manesiotis, P. McCabe, T. Tajber, L. Corrigan, O.I. Healy, A.M.
Grossjohann, C.
Serrano, D.R.
Paluch, Krzysztof J.
O'Connell, P.
Vella-Zarb, L.
Manesiotis, P.
McCabe, T.
Tajber, L.
Corrigan, O.I.
Healy, A.M.
Publication Date
2015-04
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© 2015 Elsevier. Reproduced in accordance with the publisher's selfarchiving
policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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openAccess
Accepted for publication
2014-12-12
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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
characterisation 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 to a physical equimolar mixture
and pure SD.
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Accepted manuscript
Citation
Grossjohann C, Serrano DR, Paluch KJ et al (2015) Polymorphism in sulfadimidine/4-
aminosalicylic acid cocrystals: solid-state characterization and physicochemical properties.
Journal of Pharmaceutical Sciences. 104(4): 1385-1398.
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Article