DISSOLUTION STABILITY OF MULTIPARTICULATE CONTROLLED-RELEASE TABLETS

Dissolution stability is evaluated on three multiparticulate membrane controlled release tablet formulations. The evaluation is based on ana lysis of the parameters in the Order Model that is used to characteriz e the dissolution profiles. By a simple statistical-graphical approach , the change during storage is evaluated, and mechanisms likely to be responsible for instability are identified. The method is more sensiti ve than the classical evaluation of dissolution data in fixed points. A high-stress condition (59 degrees C/ambient humidity in 10-21 days) was used to make the tablets unable to disintegrate. Dissolution profi les from these tablets were fitted to the Order Model thus showing how the parameters are affected by slow and incomplete disintegration. Th is knowledge facilitated interpretation of 40 degrees C storage data a s the observed effects could be differentiated into disintegration-rel ated and release mechanism-related. For the three tested products, the stability analysis showed that the disintegration properties play a p redominant role for the dissolution stability. (C) 1997 Elsevier Scien ce B.V.