Enhancing Adamantylamine Solubility through Salt Formation: Novel Products Studied by X-ray Diffraction and Solid-State NMR

authors	Martins, ICB; Sardo, M; Alig, E; Fink, L; Schmidt, MU; Mafra, L; Duarte, MT
nationality	International
journal	CRYSTAL GROWTH & DESIGN
keywords	ACTIVE PHARMACEUTICAL INGREDIENTS; CRYSTAL-STRUCTURE; PACKING INTERACTIONS; CARBOXYLIC-ACIDS; SACCHARIN SALTS; COCRYSTALS; AMANTADINE; FORMS; CRYSTALLOGRAPHY; HYDROCHLORIDE
abstract	The reactivity of the neuroleptic drug adamantylamine toward aliphatic carboxylic acids, sulfone derivatives, and aromatic amino acids was screened for the first time using simple mechanochemical methods. Seven new molecular salt structures were reported exhibiting improved physicochemical properties. To carefully characterize these compounds, multiple complementary techniques were combined: single crystal and powder X-ray diffraction, C-13/N-15 solid-state NMR, and Fourier transform infrared-attenuated total reflectance spectroscopies, employed to solve cocrystal/salt ambiguities. In all molecular salts, the crystal packing is supported on a common synthon, a N-H-(ADA)(+)center dot center dot center dot O-(coformer)(-) charge assisted hydrogen bond. Different supramolecular arrangements obtained induced by the size of the counterions as well as their complementary functional groups. Two salts, with glutaric and methanesulfonic acids, presented higher solubility than the commercially available pharmaceutical product.
publisher	AMER CHEMICAL SOC
issn	1528-7483
isbn	1528-7505
year published	2019
volume	19
issue	3
beginning page	1860
ending page	1873
digital object identifier (doi)	10.1021/acs.cgd.8b01830
web of science category	Chemistry, Multidisciplinary; Crystallography; Materials Science, Multidisciplinary
subject category	Chemistry; Crystallography; Materials Science
unique article identifier	WOS:000460996600048