Effects of grinding and tableting on physicochemical stability of an anticancer drug, TAT-59.
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.
Pharmaceutical Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Y
Y
Matsunaga
N
N
Bando
H
H
Yuasa
Y
Y
Kanaya
D000970:Antineoplastic Agents / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D004355:Drug Stability; D010316:Particle Size; D013499:Surface Properties; D013607:Tablets; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry; D013696:Temperature
D000970:Antineoplastic Agents; D013607:Tablets; D013629:Tamoxifen; C064635:TAT 59