Study On The Preparation Of Omeprazole Sodium Solvates

Omeprazole sodium(OMS)is a gastric proton-pump H+/K+-ATPase inhibitor which can control of gastric acid secretion.It is an effective drug widely used in the treatment of acid peptic disorders.As a model polymorphic compounds,OMS exists at least 11 polymorphs.In this thesis the preparation of OMS solvates were systematically studied as follows.According to the molecular structure of OMS,some solvents were selected for slurring crystallization experiments.Six new OMS solvates were prepared includes hemihydrate,1,2-ethanediol solvate,formamide solvate,methanol solvate,1,2-propanediol solvate and ethanol-actone solvate.The single crystal structure of OMS methanol solvate was solved for the first time.From the perspectives of the assembly process on a molecule level and supramolecular level,the important role of methanol on the crystal formation was explored.Thermal analysis and VT-PXRD analysis demonstrated that the crystal would not exist once the solvent methanol was removed.The properties of the solvents which could form the corresponding OMS solvates were summarized,including molecular volume,polarity,hydrogen bond donor capacity,electron pair donor ability.FT-IR analysis demonstrated that the obtained OMS solvates have similar host-guest intermolecular hydrogen bond patterns through which the solvent molecules bridge the OMS molecules into 3D periodic arrangements.The static method coupled with dynamic method was used to measure the ternary phase diagram of OMS-Methanol-Water system at 20 oC.The ternary phase diagram showed that OMS methanolate and OMS monohydrate can transform into each other directly.The composition of the eutonic point was determined.There is no crystallization region of OMS nonsolvate in the phase diagram which implies that the OMS nonsolvate could not be prepared through solution crystallization in methanol-water mixtures.