丙氨酰谷氨酰胺溶液预冻方式对冻干样品结晶度的影响

The Effect of Pre-freezing Method on Crystallinity of Alanylglutamine

目的研究和调节丙氨酰谷氨酰胺冻干样品的结晶度及粒度均一性,为冻干工艺研究和产业化奠定基础。方法用扫描电镜、X-射线粉末衍射、差示扫描量热、热重分析和冻干实验分别研究了快速降温预冻和多次变温退火预冻对丙氨酰谷氨酰胺冻干样品结晶度及结晶粒度的影响。结果扫描电镜结果揭示了快速降温预冻后丙氨酰谷氨酰胺冻干样品的颗粒细小,结晶度低,但经多次变温退火处理后,冻干样品结晶粒度均一,结晶度高;X-射线粉末衍射结果和差示扫描量热分析结果均说明多次变温退火预冻方式较快速降温预冻方式更有利于丙氨酰谷氨酰胺形成结晶粒度均一、晶体缺陷少、结晶度高的冻干样品;热重分析的实验结果表明,经过快速降温预冻再冻干的丙氨酰谷氨酰胺样品热稳定性差;多次变温退火预冻再冻干的丙氨酰谷氨酰胺样品热稳定性好。结论最终的真空冻干实验证明,多次变温退火预冻不仅提高了丙氨酰谷氨酰胺冻干样品的质量和冻干效率,节约了成本,还达到生产节能降耗的最终目的。

OBJECTIVE To research and regulate the crystal quality of alanylglutamine for improving their stability and pharma- codynamies as well as vacuum freeze-drying efficiency. METHODS Scanning electron microscopy （SEM） , X-ray powder diffractom- eter （XRD） , differential scanning calorimetry （DSC）, and thermogravimetrie analyzer （TG） as well as lyophilized experiments were used to investigate the effect of pre-freeze method on crystallinity and uniformity of particle size of alanylglutamine. RESULTS The result of SEM revealed that the lyophilized alanylglutamine with accelerated pre-freeze method is small-size particle with low crystallini- ty. Then the lyophilized alanylglutamine with multi-step annealing pre-freeze method become uniformly large particle with high crystal- linity. The results of XRD and DSC indicted that, comparing with the lyophilized alanylglutamine with accelerated pre-freeze method, the lyophilized sample with multi-step annealing pre-freeze method is easier to form the crystal medicine with uniform particle size, less crystal defects, high erystallinity. And the former has lower stability than the later. CONCLUSION The final lyophilized experiment give us a conclusion that using the multi-step annealing pre-freeze method can improve the freeze-drying efficiency and crystal quality of alanylglutamine, which to achieve the ultimate goal of cost and energy saving.