氨苄青霉素钠的多晶型与稳定性研究

经X线粉末衍射、扫描电子显微镜等仪器的测试,检测出氨苄青霉素钠存在A,B和C三种晶型。52%相对湿度的吸湿试验和热稳定性加速试验,从动力学证明C型晶体稳定性相对较好,A型和B型其次,无定形最差。溶解热的测定从热力学证明结晶型具有相对较低的内能,无定形较高,所以无定形稳定性较差。热稳定性加速试验中,根据初均速原理,用青霉素自动分析仪对含量变化作测定,使结果较好地满足Arrhenius方程式。本试验方法较简便,并且有较好的精度和重演性。通过本项工作,对不同晶型的氨苄青霉素钠样品的稳定性优劣作出了判别,为提高产品质量提供了部分依据。

POLYMORPHISM AND STABILITY OF AMPICILLIN SODIUM

This paper reports studies on the relationship between polymorphism and stability of ampicillin sodium(69-52-3) (Ⅰ) for improving its property in solid state, and providing an easy and precise method to predict the shelflife of drugs.The three polymorphie modifications, A, B and C, and an amorphism of (Ⅰ) were analyzed by X-ray diffraction, IR, DTA, polarizing microscopy, electronscanning microscopy and NMR. The modifications A, B and C are crystallized from iso-propanol, dichloromethane and acetonitrile systems, respectively, while the amorphism is produced either by freeze drying or by spray drying.By means of the moisture-absorption test in RH: 52% and the thermal stability test, it was dynamically demonstrated that the modification C is far more stable than the modifications A and B, and the amorphism is the least stable. Through determining the heat of solution, it was found that (Ⅰ) in any Crystal modifications possesses less internal energy than the amorphism. Due to this, it was thermodynamically proved why the crystal modifications are more stable than the amorphism. In the thermal stability test, the method known as the rule of initial equal speed was used, thus the shelflife of drugs can be easily predicted without predetermining the order of reaction.Thus, it may be stated that improving the stability of (Ⅰ) in solid state can be achieved by changing its crystal modification.