A new organic salt and a cocrystal
of the antidiabetic drug chlorpropamide
(cpa) were obtained by mechanochemical liquid-assisted
grinding (LAG) with several cocrystal formers. An organic salt was
formed with 4-(dimethylamino)pyridine (cpa:DMAP)
and a cocrystal was obtained with 4,4′-dipyridyl (cpa:BP). After extensive screening for polymorphism/stoichiomorphism, two
polymorphs of the cpa:DMAP salt (Forms I and II)
and one form of the cocrystal cpa:BP were discovered. cpa:DMAP-I crystallized with eight molecules in the asymmetric unit (Z′ = 4, Z″ = 8), whereas cpa:DMAP-II crystallized with two molecules in the asymmetric
unit (Z′ = 1, Z″ =
2). The new forms were characterized via single-crystal X-ray diffraction
and powder X-ray diffraction along with thermal methods of characterization.
Additionally, the various conformers found in these multicomponent
forms are analyzed and compared to the known polymorphs of cpa. Finally, we show that the stable polymorph of the salt cpa:DMAP-I has a drastically enhanced aqueous solubility
and dissolution rate relative to the pure cpa, thus
giving it an advantage for improved drug delivery.
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