(M1530-01-05) Evaluation of a TiO2-Free PVA-Based Film Coating System with Improved Opacity and Color Uniformity

Purpose: Film coatings include materials to provide opacity, help color matching, and protect active ingredients from light-induced degradation. Titanium dioxide (TiO2), classified as E171 when used as a pigment in foods, is the best and preferred whitener and opacifier for pharmaceutical and nutraceutical applications. Since the use of TiO2 as a food additive was suspended in Europe in 2022, companies are required to explore alternative materials to replace TiO2 with same or similar functionalities. However, TiO2-free PVA-based systems, using ingredients such as calcium carbonate, have significantly lower opacity and color uniformity compared to HPMC-based systems. As a result, most available TiO2-free systems with good opacity in the market are HPMC-based. The objective of this study was to evaluate an optimized PVA-based TiO2-free coating with high opacity and improved color uniformity.

Methods: Opacity Testing: In this study, a black film coating was applied to 350mg placebo tablets (at 15% solids, 3%WG) and then these black tablets were used for opacity testing of the following white film coating systems: PVA-based formulation containing TiO2; PVA-based formulation replacing all TiO2 with calcium carbonate; New optimized PVA-based TiO2-free formulation. Each formulation was top-coated at 20% solids onto 3 kg of black sub-coated placebos in a 15” fully perforated side-vented coating pan from O’Hara Technologies (Labcoat II). Samples were taken at 3, 4, and 5% theoretical weight gains. The top-coated black tablets were measured using a Datacolor spectrophotometer and the L-values were recorded (n=10). The L-value indicates the lightness of the sample from 0 to 100, with higher numbers representing whiter and therefore, more opaque film coat. Color Uniformity Testing: In this study, the following formulations were tested: PVA-based formulation containing TiO2 with FD&C Blue #2 Aluminum Lake (Blue #2); PVA-based formulation containing calcium carbonate with Blue #2; New optimized PVA-based TiO2-free formulation with Blue #2. Each formulation was coated at 20% solids onto 17kg of 500mg acetaminophen caplets in a 24” fully perforated side-vented coating pan from O’Hara Technologies (Labcoat II). Samples were taken at 3, 4, and 5% weight gains. Datacolor spectrophotometer was used to measure Delta E (DE) values for each individual caplet (n=20) versus a reference standard (5%wg average). In this case, DE values greater than 2.5 suggest that non-uniformity of color would be visually apparent.

Results: Opacity: The optimized PVA-based TiO2-free formulation and the PVA-based formulation containing TiO2 look white suggesting that both systems have sufficient opacity and whiteness to hide the color of the black sub-coat, with the TiO2-free formulation being only slightly darker. In contrast, the PVA-based formulation containing calcium carbonate has a significant dark gray tint suggesting poor opacity (Figure 1). The L-Values from Datacolor measurements showed that the PVA-based formulation with TiO2 has significantly better opacity compared to the PVA-based formulation containing calcium carbonate, with a 28-unit difference at 4% WG. The optimized PVA-based TiO2-free formulation is much closer in opacity to the PVA-based formulation with TiO2, with an 8-unit difference at 4% WG. The optimized formulation has significantly better opacity compared to the PVA-based formulation containing calcium carbonate, with a 20-unit difference at 4% WG (Figure 2). These results match the visual observations as shown in Figure 1. Color Uniformity: Color uniformity of the different formulations containing Blue #2 at 3, 4, and 5% WG on acetaminophen caplets are shown in Figure 3. The PVA-based formulation with TiO2 has the best color uniformity, reaching the acceptable limit (DE < 2.5) at 3% WG with little variation within samples. The PVA-based formulation with calcium carbonate requires more than 5% WG to reach sufficient color uniformity and has much larger variation within samples. The optimized PVA-based TiO2 free formulation has good color uniformity, reaching the acceptable limit at 4% WG and lower variation at all weight gains compared to the PVA-based with calcium carbonate (Figure 3).

Conclusion: This study shows that the new optimized PVA-based TiO2-free formulation achieves good opacity and color uniformity at 4% WG. This is a significant improvement compared to other PVA-based TiO2-free systems. This formulation was designed specifically to meet consumer demands, and to prepare for any possible regulatory changes in Europe regarding the use of TiO2 in pharmaceutical products.


Tablets with 4% Weight Gain Top-coat on Black Coated Placebos


L-Values for Black Sub-coated Placebos with Top-Coats at Different Weight Gains


DE Values for Acetaminophen Caplets Coated with Blue #2 Formulations at Different Weight Gains