Structure determination and in vitro/vivo study on carbamazepine-naringenin (1:1) cocrystal

Cocrystallization between a BCS II class drug, carbamazepine, and polyphenolic compounds such as naringenin and naringin, is performed in the present study. New carbamazepine-naringenin (CBZ-NRG) cocrystal with 1: 1 molar ratio was obtained and characterized by using the methods of X-ray diffraction, nuclear magnetic resonance (solid state ¹³C-NMRand liquid ¹H NMR), thermal and spectral analyses (FT-IR and solid state fluorescence). CBZ-NRG crystallizes in the P2₁/c space group, which belongs to monoclinic system. The molecular interactions were elaborated in the packing diagrams and confirmed by solid state ¹³C NMR and FT-IR methods. It is scarce that CBZ-NRG cocrystal presents higher endotherm (T_onset = 272.7 °C) than both starting materials (T_onset = 188.6, 248.6 °C) using DSC analysis. The fluorescence values of CBZ-NRG cocrystal (179 A.U.) decreases significantly in comparison with CBZ (6121 A.U.). The in vitro/vivo assessment of NRG effect on CBZ was conducted in the present study. Compared with CBZ (97.2 ± 1.5 μg/mL) in water the solubility of CBZ-NRG cocrystal decreases to 7.2 ± 0.6 μg/mL, the same trends in pH = 1.2 and 6.8 buffer solution. The IDR values of CBZ and CBZ-NRG cocrystal are 0.042 and 0.016 mg/cm²/min respectively. Interestingly, CBZ has one absorption peak while the CBZ-NRG cocrystal has double absorption peaks in plasma concentration-time curves. The peak concentration (C_max = 491.3 ± 97.6 ng/mL) of CBZ-NRG cocrystal decreases with longer elimination half life (t_1/2 = 8.5 ± 1.0 h) in comparison with CBZ (C_max = 5258.1 ± 904.2 ng/mL, t_1/2 = 0.7 ± 0.2 h). The obtained results suggest that CBZ-NRG cocrystal presents different in vitro/vivo performance in comparison with CBZ.