(T1230-11-76) Calcium Carbonate as an Alternative to Titanium Dioxide in Coating: The Importance of Particle Engineering

Purpose: Uniform colored and white coatings applied to tablets create a homogeneous appearance across batches, improving aesthetics and patient compliance. Titanium dioxide is used extensively in solid dosage forms for this purpose, serving as an opacifier and colorant. Due to its high refractive index, it provides highest opacity and coverage for a coating. Based on a safety assessment of titanium dioxide (E171) by the European Food Safety Authority (EFSA)¹ regarding concerns about potential genotoxic effects, the EU Commission has withdrawn the authorization to use titanium dioxide in foods and dietary supplements. The ban of titanium dioxide became effective in August 2022 based on the Commission Regulation (EU) 2022/63 and its removal from pharmaceutical products in the EU is now being considered.² Given these regulatory trends, there is a need to identify sustainable replacements for titanium dioxide. With the current approval status as the only other white drug colorant in the EU, calcium carbonate (CaCO₃) is seen as the most likely alternative. Parteck^® TA excipient - a calcium carbonate with a defined morphology and particle size distribution - has been developed for use in tablet film coatings and addresses the need for both good opacity and process efficiency. This poster highlights how particle-engineering supports an optimal performance of calcium carbonate in coating application.

Methods: Particle properties of the calcium carbonate were measured by scanning electronic microscopy (SEM): Tescan VEGA3 XMU, W cathode, low vacuum, high vacuum, accelerating voltage 0.2 kV to 30 kV, YAG BSE detector, SE detectors. Powder x-ray diffraction (PXRD, STOE GmbH) was used to identify the morphology; parameters: 40kV, 40 mA. Color cards were prepared using a film cast unit from Moeller, CI-K3-125-M. For the preparation of the coating solutions, a 20% polyvinyl alcohol-based solution was mixed with different amount of CaCO₃ 3300 rpm, 2 min (Hauschild Engineering, SpeedMixer DAC 150). The viscosity was measured with Thermo-Fisher Haake Mars Rheo 60 Measuring Geometry (P25/Ti Gap: 0,1 mm CR; ɣ̇ 100,0 1/s; t 60,00 s; T 20,00 °C). Composition of core tablet formulation: 98.5 % mannitol containing core tablets with 1.5% lubricant produced with 11.0 mm round on SC punches. The white cores were coated with a coating suspension with 10 % w/w iron oxide black in an aqueous medium with 5% w/w weight gain. In this study the CIELab-based method was used to measure the tablet colors. The 3D color space is defined by the axes L*, a* and b* with each representing a quantitative measurement of lightness (L*), a* (redness-greenness) and b* (blueness-yellowness). The L* value of 100 refers to the ideal absolute white color, whilst the L* value of 0 refers to the ideal absolute black.

Results: The benchmark overview of calcium carbonate grades shows that the particle engineered CaCO₃ provides a specific pattern of crystallinity in the diffractogram which corresponds to the morphology of calcit with rhombohedral structure and frequently hexagonal crystals. The unique particle size distribution (PSD range) enables good opacity and surface characteristics. Despite a higher solid content of CaCO₃ in the solution, which is necessary for comparable coating results in some cases, the particle engineered CaCO₃ has no influence on viscosity in comparison to basic PVA coating solutions with TiO₂. According to the results for the coated core tablets, a weight gain of 5- 8% can lead to a good opacity and a good covering of the initial black tablet cores.

Conclusion: It could be demonstrated that a defined particle size distribution as well as a unique crystalline structure of the calcium carbonate enables a uniform finishing and good opacity. For strong pre-colored core tablets, a higher amount of calcium carbonate is required to achieve a level of covering comparable to titanium dioxide containing film coatings. The low viscosity of the spraying liquid at higher solid contents helps to maintain a good process efficacy. When combined with the PVA-based polymer, enhanced opacity can be achieved compared to standard HPMC based formulations. Use of screening via film casting methods can enable formulators to rapidly assess the performance of film coating formulations. The proposed color measurement technique represents a suitable tool to quantify opacity and whiteness and can be utilized to optimize the final finishing in the formulation development.

References: 1 European Food Safety Authority (EFSA), Safety assessment of titanium dioxide (E 171) as a food additive, adopted 25 March 2021
EFSA Journal Volume 19 (May 2021)
2 Commission Regulation (EU) 2022/63 of 14 Jan 2022
Official Journal of the European Union L 11/1 (18 January 2022)

Figure 1: Graphical abstract of the established formulation development approach.