Titanium Dioxide in Pharmaceutical Products: A Permissible Daily Exposure Conundrum

Purpose

Titanium dioxide finds widespread application in the pharmaceutical industry as a white pigment in capsule shells, film, and sugar coating compositions. Based on the EFSA (European Food Safety Authority) investigation, the European Commission recently revoked license to use titanium dioxide in food products. Subsequently, major regulatory agencies have reviewed the safety of titanium dioxide in pharmaceutical products and based on well-designed in vitro and in vivo studies, they determined that titanium dioxide poses no safety concern. The practicality of replacing titanium dioxide or omitting it from formulations was determined to have a detrimental influence on the quality, safety, and efficacy of pharmaceutical products. Controlling titanium dioxide levels in formulations to safe levels, on the other hand, could be a realistic strategy of reducing patient exposure to titanium dioxide while maintaining compliance to product critical quality attributes. This article examines the safety of using titanium dioxide in pharmaceutical products while taking into account the worst-case scenario, which is higher daily intake of titanium dioxide via pharmaceutical products.

Methods

Depending on the NOAEL (no observed adverse effect level) reported in various studies, or the safe threshold advised by regulatory bodies, various scenarios for calculating the PDE (permissible daily exposure) of titanium dioxide in pharmaceutical products are discussed.

Results

Titanium dioxide does not pose a risk to human health at the current level of use in pharmaceutical products.

Conclusion

As suggested by the titanium dioxide alternative consortium, a PDE-based control strategy would be desirable.