Evaluating the color stability of titanium dioxide-free film coats under environmental and light stress

Titanium dioxide (TiO2) is an opacifier/colorant in tablet film coatings and capsule shells. Recently, questions about its safety have raised concerns that it may be banned from medicinal products in the European Union (EU); however, little information exists on alternatives to enable the pharmaceutical industry to pivot. This study evaluated color stability of film coats containing alternate opacifiers, calcium carbonate (CaCO3) and rice starch. Placebo tablets were coated with film coating systems containing different polymers (hydroxypropyl methylcellulose (HPMC) or polyvinyl alcohol (PVA)), opacifiers (CaCO3, rice starch, or TiO2) and pigments (FD&C Blue No. 2, iron oxides, or non-pigmented); the coated tablets were exposed to environmental stress (temperature/humidity) and light stress and color changes were quantified spectrophotometrically.The HPMC-formulated coats containing CaCO3 or rice starch showed comparable stability to TiO2. The PVA-based coats containing FD&C Blue No. 2 or iron oxide colorants exhibited color changes when exposed to elevated temperature/humidity, which were more pronounced with CaCO3 than with TiO2. No meaningful color changes were observed under white or UV light stress for any coat. This study demonstrated PVA coating systems pose a stability risk, whereas these alternate opacifiers presented an overall low color stability risk, offering potential TiO2 alternatives.