Effect of pH and β-cyclodextrin on the photophysical properties of lamotrigine

Abstract

Photophysical properties of lamotrigine (LMT) were investigated at different pH values. Lamotrigine exhibited a broad absorption band at 308 nm that was shifted to 268 nm at pH 2.0 due to protonation (HLMT+). Emission spectra of LMT at different pH values showed a single band at 483 nm except for at pH 2.0, where a second band at 502 nm was observed due to the deprotonation from the singlet excited state. LMT pH profile was used to calculate pKa of LMT in excited and ground states (pKa* = 4.50 and pKa = 5.90). Absorption spectra of LMT at different pH values for LMT in the presence of β-CD showed an isosbestic point at 290 nm. A significant enhancement in the emission intensity of LMT upon increasing β-CD (0–7 mmol L−1) was reported. Benesi–Hildebrand analysis showed that LMT/β-CD and HLMT+/β-CD complexes have 1:1 stoichiometry, with K11 values ranging from 122 at pH 2.0 to 50 at pH 8.0. Thermodynamic parameters showed that complexation process is enthalpy driven (∆H◦ = −23.1 kJ.mol−1 at pH 2.0 and –24.1 kJ.mol−1 at pH 8.0). Molecular mechanical calculations by MM+ force field indicated that LMT is preferentially included within the β-CD cavity through its diamino-1,2,4-triazine moiety.