Terahertz Spectroscopy of Lamotrigine and Phthalimide co-Crystals

Lamotrigine is a prescribed pharmaceutical for the treatment of epilepsy, convulsions, and other symptoms, but it has low solubility in water. Pharmaceutical cocrystals, as a new solid form of drugs, are formed through the non-covalent bonding of active pharmaceutical ingredients ( API ) and cocrystal formers (CCF). This non-covalent bonding can alter the internal structure of drug molecules and the weak intermolecular interactions, effectively improving the physicochemical properties of APIs, such as solubility, stability and bioavailability. In this article, lamotrigine-phthalimide-phthalimide co-crystals were investigated using terahertz time-domain spectroscopy (THz-TDS). Initially, the experimental THz spectra of lamotrigine, phthalimide, their physical mixture and the cocrystals were measured in the 0.5-5.0 THz range. Experimental data reveal new absorption peaks at 2.18 and 2.49 THz in the co-crystal , indicating that THz-TDS-TDS can effectively distinguish lamotrigine, phthalimide, and their co-crystals. Structural optimization and spectral simulation were carried out on the constructed theoretical form and periodic structure using density functional theory, and the calculated results can effectively reconstruct the experimental spectrum. Through the discussion and analysis of the origins of THz absorption peaks in co-crystals , it is found that the intermolecular forces of lamotrigine-phthalimide-phthalimide co-crystals mainly originate from pi - pi stacking force, and hydrogen bonding contributes slightly.