STUDIES ON INTERNAL STRUCTURE .7. 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, xy]phenyl]-2-(4-isopropyl)phenyl]-1-butenyl]phenyl monopho sphate, were studied, The crystallinity of TAT-59 ground in a planetar y ball mill for 0-120 min or compressed at 0-4500 kg/cm(2) was evaluat ed by X-ray diffraction analysis and differential scanning calorimetry (DSC), The surface of TAT-59 was measured under a scanning electron m icroscope (SEM), The physicochemical stability of TAT-59, ground or co mpressed, was determined by measurements of water content, crystallini ty and the amount of hydrolysis product, DP-TAT-59, formed, The crysta llinity 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 finding s suggested that the decrease of the crystallinity of TAT-59 by mechan ical force, such as grinding and tableting, raised the drug's reactivi ty and affected its stability.