Ethinyl estradiol cocrystals assembled by chains structures: improvement in stability and solubility
Cocrystals of ethinyl estradiol (EE) with five coformers including nicotinamide (NA), piperazine (PZ), tetramethylpyrazine (TET), 4,4'-bipyridine (BIP) and imidazole (IZ) had been prepared with 1:1 stoichiometry, and their crystal structures were characterized by a series of physicochemical methods. EE molecules were connected with coformers through intermolecular hydrogen bonds and formed chain structures. Especially, EE-NA and EE-TET‧H2O had special spiral chain structures and unique combinations. The physical stability experiment under high temperature, high humidity and high light intensity conditions proved the stability of EE cocrystals. Meanwhile, the dissolution performance had been explored, and a prominent “spring-parachute” effect was observed for EE-NA at 0.2% SDS solution to improve the EE solubility (1.43-fold), EE-PZ and EE-TET‧H2O also had advantage over EE. This successful attempt implies that cocrystal strategy is effective means to improve the solubility and stability of EE.