Matrix formation in sustained release tablets: possible mechanism of dose dumping.

Conditions under which poly(ethyl acrylate, methyl methacrylate) 2:1 (poly(EA-MMA), Eudragit NE) forms a stable matrix were investigated in tablets with diclofenac sodium (DS) as an active substance. DS was granulated with the aqueous polymer dispersion. Granules and/or tablets were cured under various temperature and humidity conditions. A six position rotating disk (200 rpm) apparatus was used for the release studies conducted in 37 degrees C acid then phosphate buffer (0.4 M) pH 6.8 or buffer only as the dissolution media. Morphological characteristics of the tablet surface were observed under SEM. Changes in tablet structure upon curing were evaluated through changes in tablet mechanical characteristics. Modulus of rupture, Young's modulus, AUC, AUC(max), where AUC=AUC(max), were determined by the three-point bending test. Some poorly cured tablets dose-dumped when placed directly into buffer but not if first placed in acid and then buffer. A higher content of polymer in the matrix, led to formation of a stronger polymer network upon higher curing temperature and/or longer curing duration, whereas relative humidity had a minor effect.