二元混合溶剂对盐酸硫胺溶剂化物稳定性及晶习的影响

Effect of binary solvent mixtures on stability and morphology of thiamine hydrochloride solvate

维生素B1是人体必需的营养物质之一,盐酸硫胺作为维生素B1的存在形式,因其空间结构不同有着不同稳定性的4种溶剂化物:盐酸硫胺半水合物(HH)、盐酸硫胺甲醇溶剂化物(MM)、非化学计量比的盐酸硫胺水合物(NSH)、无水盐酸硫胺(AH)。制药行业致力于寻找一种相对稳定的盐酸硫胺,以便于生产、储存和运输。采用悬浮转晶的方法制备了4种盐酸硫胺溶剂化物,从分子层次探究4种溶剂化物的稳定性,得出盐酸硫胺半水合物因其内部强氢键作用力而最稳定的结论。同时,探讨了二元混合溶剂对盐酸硫胺4种溶剂化物稳定性的影响,确定了不同溶剂化物稳定存在的适宜条件。采用BFDH模型模拟了盐酸硫胺甲醇溶剂化物的晶习,发现BFDH模型的模拟结果与实际晶习一致,为工业溶剂筛选以获得目标产品提供理论指导。

Vitamin B1 is one of the most essential nutrients in human bodies. Thiamine hydrochloride, a form of vitamin B1, has four solvates, hemihydrate（HH）, methanol solvates（MM）, nonstoichiometric hydrate（NSH）, and anhydrous form（AH）. These four solvates have different stabilities because of different space structures. In that way, a stable solvate which has better properties of production, storage and transportation is investigated by drug industry. In this paper, X-ray diffraction and thermal analysis were measured and crystal form transformation experiments in methanol-water and methanol-ethyl acetate were investigated. It can be seen that hydrate hemihydrate is more stable because of hydrogen bonds. Moreover, molecular dynamics simulation by using BFDH and AE model of MM in methanol-ethyl acetate binary solvent mixtures was calculated. The result shows that BFDH model matches real crystal habit, which could guide industrial production.