Isomorphous pharmaceutical salts of lamotrigine with counterion dependence on water solubility

Abstract

The process of molecular recognition in inclusion compounds is governed by the intermolecular interactions which occur between the various host and guest molecules making up the resultant crystalline assembly. We have studied the diol host, 2,2'-bis (hydroxydiphenylmethyl-1,1'-binaphthyl(H), which crystallised in three different polymorphic structures and formed a series of inclusion compounds with pyridine(P), morpholine(M) and benzene(B). Different stoichiometries were obtained by manipulating the proportions of the guests and the crystallisation temperatures. Four of these inclusion compounds, H.3P, H.2P.M, H.2P.B and H.P.M.B, are isomorphous and the guests are located at fixed sites in the crystal structure. Their thermal analysis results were explained in terms of the host guest interactions. The three polymorphs of the host compound show strong structural similarities as depicted by their Hirshfeld surface fingerprint plots, which exhibit dominant H H interactions. The conformation of the host molecule remains essentially constant, and is governed by an intramolecular O-H O hydrogen bond in the polymorphs of the apohost and in all the nine inclusion compounds analysed.