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

Abstract

Lamotrigine (L) is a known drug in the treatment of epilepsy and bipolar disorder. Due to its unique structure and functionalities, L is able to form both salts and cocrystals. The present study reports ionic, neutral, and hybrid crystalline forms of L with improved material properties and modified drug release rates. Novel forms of L with cinnamic acid (CA), ferulic acid (FRA), salicylic acid (SAC), and vanillin (VN) were successfully prepared and characterized using single crystal XRD, SEM, FT-IR, DSC, TGA, and powder XRD. LCA and LVN crystallized in P21/c space group, whereas LSAC crystallized in P1¯ space group. Pseudo-quadruple hydrogen bond with R42 (16) graph set notation were observed in all three crystal structures of L. The characteristic FT-IR stretching peaks at 3326.53, 3341.53, and 3340.65 cm-1 corresponding to N+-H bond were observed in LCA, LFRA, and LSAC. Comparison of dissolution profiles using similarity factor (f2) analysis revealed that the dissolution profiles of LCA, LFRA, and LVN were significantly different from that of L. LVN exhibited improved dissolution rate compared to L and LCA revealed a sustained release profile. Both these properties are important in designing oral dosage forms for neuropathic pain and bipolar disorder therapy. Further, LCA can be used in the development of extended release drug delivery systems for treating epileptic disorders.