Thermodynamics of baicalein-nicotinamide co-crystallization process / 中国药科大学学报

ABSTRACT

Baicalein-nicotinamide(BE-NCT)co-crystal was chosen as model drug to investigate the thermody-namic characteristics.Solubilities of BE in NCT solutions in ethyl acetate at different temperatures were deter-mined in order to explain the complexation behavior of BE-NCT co-crystal.Thermodynamic parameters of co-crys-tal formation progress were calculated.Ternary phase diagrams (TPDs)of the BE-NCT-ethyl acetate systems at various temperatures were established.The non-linear fitting equation according to 1 ∶1 complexation mechanism of BE-NCT co-crystal demonstrated a good correlation between calculated and experimental data (R2 >0.98). Co-crystal formation is a spontaneous process(ΔG°<0).Increase in temperature resulted in the increase of Ksp;decrease of K11 and a narrowed co-crystal zone.The degree of spontaneous reaction also decreased with increased temperature.The spontaneous reaction no longer carried out if the temperature reached T* =315 K sinceΔG°=0(ΔH°=-6.314 ×10 -2 kJ/mol;ΔS°=-0.200 5 J/mol.K).A drop in temperature favors the complexation between BE and NCT in ethyl acetate.Since NCT has higher solubility than BE in ethyl acetate;the TPDs of co-crystal was asymmetric.The DSC diagrams of products prepared via three presupposed methods confirmed that the BE-NCT co-crystal could be generated in solutions of nonstoichiometric compositions.