Effects of Grinding and Tableting on Physicochemical Stability of an Anticancer Drug, TAT-59

概要

論文の詳細を見る
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/cm^2 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 dacrease of the crystallinity of TAT-59 by mechanical force, such as grinding and tableting raised the drug's reactivity and affected its stability.
公益社団法人日本薬学会の論文
1996-10-15