Studies on Internal Structure of Tablets. Part VIII. Melting Granulation by Addition of Polyethyleneglycol for Stabilization of TAT-59.

Compatibility of (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropylphenyl)-1-butenyl]phenyl mono-phosphate, TAT-59, with excipients was studied by using a powder mixture, a tablet obtained by compressing the powder mixture and powder obtained by crushing the tablet. TAT-59 with excipients of kinds of cellulose, sugar and starch degraded, whereas TAT-59 with polyethyleneglylcol 6000 (PEG6000) was stable. Stability of the tablet consisting of TAT-59 and microcrystalline cellulose (MCC) obtained by the direct compression method (T-TM), the tablet consisting of TAT-59, MCC and PEG6000 by the direct compression method (T-TMP) and the tablet consisting of TAT-59, MCC and PEG6000 by the melting granulation method (T-MG) was evaluated by determining the formation of its hydrolysis product, DP-TAT-59. The degradation rate decreased in the order : T-TM>T-TMP>T-MG.Thus, the melting granulation method with the addition of PEG6000 was found to stabilize the tablet containing TAT-59. The reason for the stabilization was presumably that the contact between TAT-59 and the water vapor or the water in MCC was decreased by coating the surface of TAT-59 and MCC with PEG6000, and that the phosphate group of TAT-59 was stabilized for the hydrogen bonding with PEG6000. Furthermore, the water-soluble PEG6000 little affected the dissolution profile of TAT-59, showing the melting granulation method can be useful for the stabilization of TAT-59.