Interaction of omapatrilat with FD&C Blue No. 2 lake during dissolution of modified release tablets.

The purpose of this study was to identify the mechanism(s) of omapatrilat degradation observed during dissolution from modified release (MR) tablet formulations containing colorants. The tablets were manufactured by a dry granulation process employing roller compaction. The colorants were added intragranularly and included red and yellow iron oxides and FD&C Blue No. 2 lake and dye. Dissolution studies in pH 6 or 6.8 media do not indicate any omapatrilat degradation in the absence of colorants. In the presence of colorants the degradation rate of omapatrilat in pH 6.8 media was in the following order: blue lake>blue lake+yellow iron oxide>yellow and red iron oxides. Higher degradation was observed with MR tablets formulated with indigo carmine (dye) as opposed to tablets formulated with aluminum oxide or aluminum hydroxide (dye substrate portion of lake). The inclusion of tartaric acid and the photostabilizer, uric acid, in omapatrilat MR tablets containing the blue lake reduced the degradation significantly. The dissolution instability observed at pH 6.8 in the MR tablet formulated with FD&C Blue No. 2 Lake was attributed to the dye component of the lake. The instability was more pronounced at higher pH and in the absence of a photostabilizer.