Observation of neutral, ionic and intermediate states in lamotrigine-acid complexes- inference from crystallographic bond geometries

Ionic, Neutral, and Hybrid Acid–Base Crystalline Adducts of Lamotrigine with Improved Pharmaceutical Performance

“…48 Few intermediate structures on L-acid complexes containing both neutral and ionic interactions falling between ΔpK a of 0.9 and 1.8 were reported recently. 24 Preliminary screening studies using solvent assisted grinding was conducted for L with various coformers like caffeic acid, CA, FRA, gallic acid, quercetin, SAC, and VN (ST 4 Supporting Information). Novel solid forms of L with CA, FRA, SAC, and VN were obtained during liquid assisted grinding wherein LCA, LSAC-ACN, and LVN systems gave single crystals.…”

“…The crystal structure of LCA was crystallized in monoclinic P2 1 /c space group. One molecule each of L and CA are present in the asymmetric unit (Figure 3a 24,50 Both L−L homo and L−CA hetero synthon hydrogen bonding motifs were observed. L homodimers were connected to CA through N−H 16) motif (Figure 3b), and the angle between two phenyl rings is 86.90°.…”

“…Sridhar et al in their recent paper reported that of all the structures of L submitted to CSD, 73% were salts, 17% were solvates and hydrates, and only 10% were cocrystals. 24 Crystal engineering strategies employed for improving pharmaceutical and biopharmaceutical performance of L include various cocrystals of L with methylparaben form I and form II, nicotinamide and its monohydrate, 25 acetamide, 26 de:DMF, caffeine:3-pentanone, isophthaldehyde, 27 and sorbic acid. 28 Salts and cocrystals of L reported until date are provided in Table S1 (Supporting Information).…”

“…The typical molecular framework seen in the structure of L makes it not only a hydrogen bond donor, but also an acceptor, and is likely to be a good target for the formation of both salts and cocrystals. Sridhar et al in their recent paper reported that of all the structures of L submitted to CSD, 73% were salts, 17% were solvates and hydrates, and only 10% were cocrystals . Crystal engineering strategies employed for improving pharmaceutical and biopharmaceutical performance of L include various cocrystals of L with methylparaben form I and form II, nicotinamide and its monohydrate, acetamide, phthalimide, pyromellitic diimide:DMF, caffeine:3-pentanone, isophthaldehyde, and sorbic acid .…”

Lamotriginium crotonate and lamotriginium salicylate ethanol monosolvate: the role of solvent molecules in the packing organization

“…On the other hand, solvated structures of similar simple acids were instead invariably packed as in salt (IV); examples are: GAVLEV (benzoate dimethylformamide solvate) in Sridhar & Ravikumar (2005), QIQHIJ (4-iodobenzoate N,Ndimethylformamide solvate) and QIQJAD (3,5-dinitro-2-hydroxybenzoate N,N-dimethylformamide solvate) in Sridhar et al (2013), WOKXUR (4-bromobenzoate dimethylformamide solvate) in Sridhar et al (2014) and YUYQEQ (salicylate acetonitrile solvate) in Thipparaboina et al (2015). This last complex, which differs from salt (IV) only in the solvent present (acetronitrile replacing ethanol), provides an opportunity to analyze the subtle role which solvents play in the final crystal structure, even in cases where large elemental motifs are shared; this latter fact is fully assessed in Fig.…”