Quantitative assessment of factors contributing to mottling of colored tablets II: formulation variables

The effects of several formulation variables were quantified with respect to factors affecting tablet mottling. Tablet mottling occurred with several commonly used binders and could not be prevented by using highly viscous binding solutions. However, mottling was reduced initially by increasing granule strength. Tablet diluents and dye-adsorbent materials had a profound effect on mottling, not by preventing dye migration but by affecting granule fragmentation on compression and the extent to which the dye-deficient material at the center of the granule was revealed. The lake form of FD&C Blue No. 1 was found to bleed in the presence of diluents that raised the pH of the granulating fluid above 6.4. Anionic impurities in the diluents also caused leaching of free dye and, consequently, increased tablet mottling. The conclusions from this study and previous papers were drawn together to give general principles for the production of uniformly colored tablets by aqueous granulation techniques.