Multicomponent Pharmaceutical Adducts of Azoxystrobin: Physicochemical Properties, Thermodynamic, and Molecular Modeling Study

Eutectics have invoked enormous interests as an inexpensive and greener excipient with promising applications. In this study, eutectics of azoxystrobin (AZO) with fludioxonil (FDO), adipic acid (AA), succinimide (SIM), and 2‐imidazolidinone (IMD) are prepared by rotary evaporation in order to improve the solubility and dissolution rate of AZO. Differential scanning calorimetry and powder X‐ray diffraction are used to distinguish eutectics. Interestingly, AZO forms form 2 at first and then forms eutectic at stoichiometric ratios of 7:3, 7:3/8:2, 7:3, and 6:4 with FDO, AA, IMD, and SIM, respectively. Compared with AZO, the solubility and dissolution rate of these four eutectics in water are improved. The molecular dynamics simulations between AZO and coformer molecules indicate that homologous hydrogen bonds are formed of conformer–coformer, which may lead to the formation of eutectic regions. Meanwhile, the interaction energies between AZO and coformers in these possible system boxes of the four eutectics are calculated. The results indicate that the interaction energy in AZO–FDO is greater than that in AZO–AA, AZO–SIM, and AZO–IMD. Four azoxystrobin eutectics are successfully obtained, and their dissolution and solubility are improved compared with azoxystrobin. The possible reasons for the formation of azoxystrobin eutectic region are explored by molecular dynamics study.