From Jellylike Phase to Crystal: Effects of Solvent on Self-Assembly of Cefotaxime Sodium

Jellylike phase (JLP) is usually harmful to the process of crystallization. The special state of cefotaxime sodium (CTX) jellylike phase and its spontaneous transition to crystals is investigated in this paper. The crystals transformed from JLPs containing different solvents have distinct habits and forms. The solvent used in JLP formation and crystallization was very important. The results show that the polarity and hydrogen bonding ability of the solvent plays a decisive role in the JLP formation and its crystallization. Combined with Fourier transform infrared spectra, in situ Raman spectroscopy monitoring experiment indicates that the orientational hydrogen bonding between the solvent and CTX molecule facilitates the construction of the CTX crystal structure. JLP crystallization offers a new way for novel polymorph development and crystal habit modification, especially for drugs that are difficult to crystallize from solution.