Lamotrigine, an antiepileptic drug, and its chloride and nitrate salts

Abstract

In lamotrigine [systematic name: 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine], C(9)H(7)Cl(2)N(5), (I), the asymmetric unit contains one lamotrigine base molecule. In lamotriginium chloride [systematic name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium chloride], C(9)H(8)Cl(2)N(5)(+).Cl(-), (II), the asymmetric unit contains one lamotriginium cation and one chloride anion, while in lamotriginium nitrate, C(9)H(8)Cl(2)N(5)(+).NO(3)(-), (III), the asymmetric unit contains two crystallographically independent lamotriginium cations and two nitrate anions. In all three structures, N-H...N hydrogen bonds form an R(2)(2)(8) dimer. In (I) and (II), hydrophilic layers are sandwiched between hydrophobic layers in the crystal packing. In all three structures, hydrogen bonds lead to the formation of a supramolecular hydrogen-bonded network. The significance of this study lies in its illustration of the differences between the supramolecular aggregation in the lamotrigine base and in its chloride and nitrate salts.

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

“…As a general observation, the bond angle with N2 atom in the middle position (A 1 ) widens upon protonation and with N2 atom in the terminal positions (A 2 & A 3 ) is narrowed. Typical bond angle values for A 1 , A 2 & A 3 are 117.0, 126.1 and 121.0°, respectively, for neutral lamotrigine [3] and 123. 4, 121.8, 116.6°, respectively, for protonated lamotrigine [20].…”

“…Lamotrigine within its molecular frame work can acts as donor as well as acceptor in the hydrogen bonding interactions and is a potential target for both co-crystal and salt formations. The CSD's 500,000 th (half-a-million) structure is the crystal structure of Lamotrigine published by us in Acta Crystallographica in 2009 [3]. The latest version of the Cambridge Structural Database (CSD Version 5.35 with November 2013 updates [4]) indicates 60 structures (excluding the parent one), which are categorized into salts (44 structures, 73%), co-crystals (6 structures, 10%) and solvates/hydrates (10 structures, 17%).…”

The Cambridge Structural Database

“…Software developed by the CCDC (i) enables the knowledge embedded in the CSD to be applied to a range of scientific problems including aiding in the determination and refinement of future structures through free resources such as CellCheckCSD (j). The flow of data is largely represented using lamotrigine (Sridhar & Ravikumar, 2009), the 500 000th entry in the CSD, CSD refcode: EFEMUX01; CCDC number: CCDC 749719; DOI: 10.5517/cct54hl. Image (a) is a crystal of p-aminobenzoic acid (Sullivan & Davey, 2015) publication year.…”

In - situ synchrotron wide-angle X-ray diffraction as a rapid method for cocrystal/salt screening

“…CAF (Enright et al, 2007) CAF-SAC (Padrela et al, 2010) CBZ (Himes et al, 1981) CBZ-SAC (Fleischman et al, 2003) LAM (Sridhar and Ravikumar, 2009) LAM-SAC (Hanna et al, 2013) SAC (Wardell et al, 2005) The 2D WAXD patterns were transformed to 1D WAXD patterns to make the phase transformation more visual. As shown in Fig.…”