Otsuka M, Matsumoto T, Kaneniwa N
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
J Pharm Pharmacol. 1989 Oct;41(10):665-9. doi: 10.1111/j.2042-7158.1989.tb06337.x.
The effects of the mechanical energy of tableting compression on the polymorphic transformation of chlorpropamide have been examined. A single-punch eccentric tableting machine with a load cell and a non-contact displacement transducer were used to measure compression stress, distance and energy. An amount of 100 mg of the stable form A or the meta-stable form C of the drug was loaded into the press and the sample compressed with a compression stress of 196 MPa at room temperature (20 degrees C). The compression cycle was repeated from 1 to 30 times. The powder X-ray diffraction profiles of the deagglomerated compressed sample powder were measured to calculate the polymorphic content. The results on forms A and C suggested that both forms were transformed into each other in the solid state by mechanical energy during tableting. The contents of forms A and C reached equilibrium at a constant value above 100 J g-1 of compression energy after more than 10 cycles. After 30 tableting cycles of forms A and C, the contents of A, C and the non-crystalline solid were almost constant at about 45, 25 and 30%, respectively. The compression energies were estimated to be about 500-600 J g-1. From the results it seems that the transformation mechanism of forms A and C during tableting were as follows. The crystal form of A or C was converted to a non-crystalline solid by the mechanical energy, and the solid was then transformed into form A or C.
研究了压片压缩机械能对氯磺丙脲多晶型转变的影响。使用带有称重传感器和非接触式位移传感器的单冲压片机来测量压缩应力、距离和能量。将100mg药物的稳定型A或亚稳定型C装入压片机中，并在室温（20℃）下以196MPa的压缩应力对样品进行压缩。压缩循环重复1至30次。测量解聚后的压缩样品粉末的粉末X射线衍射图谱，以计算多晶型物含量。关于A和C型的结果表明，在压片过程中，两种晶型在固态下通过机械能相互转化。在超过10个循环后，当压缩能量高于100J g-1时，A和C型的含量达到恒定值的平衡状态。对A和C型进行30次压片循环后，A、C和非晶态固体的含量分别几乎恒定在约45%、25%和30%。估计压缩能量约为500 - 600J g-1。从结果来看，压片过程中A和C型的转变机制如下。A或C的晶型通过机械能转化为非晶态固体，然后该固体再转化为A或C型。
