Ishida Hajime, Wu Tian, Yu Lian
School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
J Pharm Sci. 2007 May;96(5):1131-8. doi: 10.1002/jps.20925.
The crystal growth of nifedipine in the beta polymorph has been measured from T(g) + 50 to T(g) - 20 K, where T(g) = 315 K is the glass transition temperature. A sudden 10-fold rise of growth rate was observed as the temperature decreased from above to below T(g) accompanied by a change of growth morphology. This is the same phenomenon reported by Oguni and coworkers [Hikima T, Adachi Y, Hanaya M, Oguni M. 1995. Phys Rev B 52:3900-3908] for other compounds of lower T(g). The phenomenon persisted in the presence of 1% polyvinylpyrrolidone (PVP). The presence of 1% or 2% PVP had little effect on the growth rate near T(g) + 50 K, but reduced the growth rate by 100-fold at T(g) + 9 K. These kinetic features are relevant to predicting the stability of amorphous drugs.
已测量了硝苯地平β晶型在从玻璃化转变温度T(g) + 50 K到T(g) - 20 K范围内的晶体生长情况，其中T(g) = 315 K为玻璃化转变温度。当温度从高于T(g)降至低于T(g)时，观察到生长速率突然升高了10倍，同时生长形态也发生了变化。这与Oguni及其同事[Hikima T, Adachi Y, Hanaya M, Oguni M. 1995. Phys Rev B 52:3900 - 3908]报道的其他玻璃化转变温度较低的化合物的现象相同。在1%聚乙烯吡咯烷酮（PVP）存在的情况下，该现象依然存在。1%或2% PVP的存在对T(g) + 50 K附近的生长速率影响不大，但在T(g) + 9 K时使生长速率降低了100倍。这些动力学特征与预测无定形药物的稳定性相关。
