(T1130-12-79) Development of Calcium Silicate Film-Coated Tablet as a Coloring Agent

Purpose: Titanium dioxide (TD) functions as an opacifier, colorant, and is widely used in pharmaceutical coatings as it maintains light and heat stability. However, the European Food Safety Authority (EFSA) has reported that TD carries a carcinogenic risk due to genotoxicity. Consequently, the European Union (EU) has announced that TD will no longer be approved as a food additive starting from August 7, 2022. In this study, various composition of the coating solution using calcium silicate (CS) was manufactured and assessed to replace titanium dioxide, which has been disapproved for food additive due to its genotoxicity

Methods: The genotoxicity of opacifier was confirmed by Quantitative Structure-Activity Relationship (QSAR) models using Derek Nexus and Sarah Nexus (Lhasa Limited). CS particles were milled using an A-O JET MILL (JS TECH CO., LTD), and the particle size of the colorant in the coating solution was assessed using a MasterSizer 3000E (Malvern Panalytical). Dispersion stability was confirmed using the LumiSizer Dispersion Analyzer (LUM GmbH). Coated tablets were prepared under specific conditions using a pan coater (HANA ADD TECH, Republic of Korea). The appearance of the tablets was observed under accelerated stability conditions (40±2℃ and RH 75±5%) for 30 days.

Results: The Derek Nexus and Sarah Nexus models indicated that CS could serve as a non-genotoxic substitute for TD. Jet milling significantly reduced the particle size of CS from a DV50 of 27.8μm to 7.11μm. This reduction in particle size led to a decrease in the transmission of the coating solution from 12% to 5% as shown by the transmission profile. Furthermore, the uniform transmittance across all sections of the cell confirmed the stability of the dispersion of the coating solution. The surface of the CS coated tablets remained undamaged under accelerated conditions.

Conclusion: In this study, we showed that CS coated tablets can be used as an alternative to TD.

References: 1) Safety assessment of titanium dioxide (E171) as a food additive. EFSA journal 2021
2) European chemical substrate information system
3) Re-evaluation of calcium silicate (E 552), magnesium ilicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and alc (E 553b) as food additives. EFSA journal 2018

Acknowledgements: This research was also supported by "Regional Innovation Strategy (RIS)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE)(2021RIS-001).

Table 1. Genotoxicity by (Q)SAR evaluation of TD and SC

Table 2. The coating formulation of the colorant

Figure 1. Coating solution dispersion stability. (a) TD 10, (b) TD 20, (c) TD 30, (d) CS 10, (e) CS 20, (f) CS 30, (g) JM -SC 10, (h) JMSC 20, (i) JMSC 30.