溶融造粒法を用いた抗癌剤TAT-59錠の安定化におけるポリエチレングリコールの分子量の影響

抄録

(E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropyl)phenyl-1-butenyl]phenylmonophosphate (TAT-59) is a new drug for the treatment of breast cancer. In the formulation of TAT-59 tablet, the melting granulation method using polyethyleneglycol (PEG) was applied to the TAT-59 tablet for stabilization, because TAT-59 was presumed to be degraded by an increase in water content and decrease in crystallinity. In this report, we discuss the effect of molecular weights of PEG on the particle diameter of the granule, the hardness, the dissolution rate, and the stability of the TAT-59 tablet made by the melting granulation method. PEG with an average molecular weight of 4,000, 6,000, or 20,000 was added to a mixture consisting of TAT-59 and microcrystalline cellulose (MCC) at various ratios. A powder mixture consisting of TAT-59, MCC and PEG was granulated by the melting granulation method, and was compressed. When the TAT-59 tablet was made by the melting granulation method using PEG of a small molecular weight, the dissolution rate of TAT-59 was enlarged. With regard to the results of the stability test, the amount of the degradation product, DP-TAT-59, decreased with increasing PEG content in the TAT-59 tablet. DP-TAT-59 increased little in TAT-59 tablets which contained PEG at more than 10%. When the TAT-59 tablet was made using PEG of a small molecular weight, the amount of DP-TAT-59 in the TAT-59 tablet became lower. The granule diameter, hardness, dissolution rate, and stability of the TAT-59 tablet obtained by the melting granulation method are considered to be influenced by melting point, melting state viscosity, and water-solubility of PEG.