Co-crystallisation of Lamotrigine with diprotic acids: synthesis, single crystal analysis, and in-vitro evaluation. (2019) - Chappa, Praveen
Abstract: The present study investigates the structural and pharmaceutical properties of two novel cocrystalsof lamotrigine (LTG) forming with maleic acid (MA) and malonic acid (MLA).Preliminary solid-state characterization was done by single crystal XRD, FT-IR, DSC and powder XRD. LTG-MA crystallized in P-1 space group whereas LTG-MLA crystallized in P21/c space group. Pseudo–quadruple hydrogen bond with R42(16) motif graph set notation was observed in all two crystal structures of LTG co-crystals. The FT-IR spectra of the two cocrystalsshowed a red shift in -NH2 stretching vibrations in the in the region of 3500-3300 cm-1, blue shift in carbonyl groups of MA and MLA in the region of 1650 to 1670cm-1 indicatesthe formation of an N-H…O=C intermolecular interaction between LTG and carboxylic acids(MA and MLA). Further, these two co-crystals were subjected to solubility, powder dissolutionstudies in 0.1 N HCl, in comparison with pure LTG base. The solubility of these compoundsin 0.1 N HCl is significantly enhanced compared with that of the pure base, which can beattributed to the type of packing motifs present in their crystal structures.