Matsunaga Y, Bando N, Yuasa H, Kanaya Y
Pharmaceutical Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Chem Pharm Bull (Tokyo). 1996 Oct;44(10):1931-4. doi: 10.1248/cpb.44.1931.
The effects of grinding and tableting on the physicochemical stability of TAT-59, (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1-butenyl]phenyl monophosphate, were studied. The crystallinity of TAT-59 ground in a planetary ball mill for 0-120 min or compressed at 0-4500 kg/cm2 was evaluated by X-ray diffraction analysis and differential scanning calorimetry (DSC). The surface of TAT-59 was measured under a scanning electron microscope (SEM). The physicochemical stability of TAT-59, ground or compressed, was determined by measurements of water content, crystallinity and the amount of hydrolysis product, DP-TAT-59, formed. The crystallinity of ground TAT-59 decreased with increasing grinding time, and the amount of DP-TAT-59 increased with decrease in the crystallinity. Similar to ground TAT-59, the crystallinity of TAT-59 tablet gradually decreased with increasing compression pressure, and the amount of DP-TAT-59 tended to increase with decreasing crystallinity. These findings suggested that the decrease of the crystallinity of TAT-59 by mechanical force, such as grinding and tableting, raised the drug's reactivity and affected its stability.
研究了研磨和压片对TAT-59（(E)-4-[1-[4-[2-(二甲氨基)乙氧基]苯基]-2-(4-异丙基)苯基]-1-丁烯基]苯基单磷酸酯）物理化学稳定性的影响。通过X射线衍射分析和差示扫描量热法（DSC）评估在行星式球磨机中研磨0 - 120分钟或在0 - 4500 kg/cm²压力下压片的TAT-59的结晶度。在扫描电子显微镜（SEM）下测量TAT-59的表面。通过测量含水量、结晶度和形成的水解产物DP-TAT-59的量来确定研磨或压片后的TAT-59的物理化学稳定性。研磨后的TAT-59的结晶度随研磨时间的增加而降低，DP-TAT-59的量随结晶度的降低而增加。与研磨后的TAT-59类似，TAT-59片剂的结晶度随着压片压力的增加而逐渐降低，DP-TAT-59的量倾向于随着结晶度的降低而增加。这些发现表明，通过研磨和压片等机械力降低TAT-59的结晶度会提高药物的反应活性并影响其稳定性。
