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 pK a of LMT in excited and ground states (pK a* = 4.50 and pK a = 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.