From the protection of active ingredients to improving patient management of medications, titanium dioxide (TiO2) plays an essential role at all stages of a pharmaceutical product’s lifecycle.
While TiO2 has long been a key ingredient in countless consumer and industrial goods, the role it occupies in the pharmaceutical industry is arguably its most vital. Thanks to its highly desirable properties, TiO2 is used in the vast majority of medicines on the market.
According to the European Medicines Agency (EMA), there is no single material that provides the same combination of properties that are unique to TiO2.
The unique beneficial properties of TiO2 in medicines
TiO2 is not only used for asthetic purposes. It performs a unique combination of key functions at all stages of a pharmaceutical product’s lifecycle. Over the course of a century this has made it indispensable to manufacturers, doctors and patients across the world, and nowadays TiO2 is almost ubiquitously present in essential medicines for humans.
Some of the key properties and applications of TiO2 include:
- Protective coatings to preserve the efficacy of medicines over time – TiO2 is an essential component of the protective coatings on medications, which enhances the safety, efficacy, and quality of pharmaceuticals for longer periods. Thanks to its ability to scatter light and absorb UV rays, TiO2 extends the shelf-life and ensures the stability of pharmaceuticals by protecting the active ingredients against UV/light and heat degradation.
- Making pharmaceuticals safer to use and easier to manage – whether it is used to add whiteness or accentuate the boldness of other colours in the protective coatings used on medications, TiO2 enables a large colour scheme and ensures that medicines maintain color uniformity over time. Colour consistency and uniformity play a significant role in the ability of patients and medical professionals to differentiate medications and dosages and safely manage their medicines. This has a direct positive impact on patient safety and adherence to prescription instructions. This is crucial for people with limited eyesight, or those that require multiple different medications or when different strengths of the same medication are available – as is the case with common blood thinner Warfarin, where four separate colours denote different dosages. Colouring is also a key indication for healthcare professionals and emergency centres in responding to cases of drug overdose or intoxication, and it can help determine if a tablet is real or counterfeit.
- Inert and effective ingredient – TiO2 is an inert and unreactive substance that does not interfere with the properties of the active ingredients of medicines nor other essential non-active components of a medicine (excipients). Only a small quantity of TiO2 is needed to achieve the desired properties. Alternative materials would need to be added in larger amounts while still not delivering the same functions that TiO2
TiO2 in medicines is safe
As a pure mineral, TiO2 meets the most stringent requirements governing the safety of medicines, including those set by the European pharmacopoeia, Japanese pharmacopoeia and US pharmacopoeia. For decades, TiO2 has built up an impressive safety record within the pharmaceutical industry.
Despite the large body of existing science and data confirming the safety of TiO2, concerns have recently been raised about the safety of TiO2 in medicines because on 14 January 2022 the European Commission issued a Regulation removing TiO2 from the approved list of food additives.
This action was based on a European Food Safety Authority (EFSA) opinion of May 2021 on the food grade of TiO2 called E171, which is also used in pharmaceuticals. EFSA did not identify any immediate health concerns linked to E171 or raise any concerns about the use of TiO2 in medicines. The EFSA took a precautionary approach because the Authority stated it could not rule out a concern about the potential genotoxicity – i.e. damage to DNA and other genetic material – from existing science.
The uncertainties raised by EFSA have been recently addressed by Health Canada, the Canadian government’s health policy department. Health Canada carried out a comprehensive review of the available science and new data generated after the EFSA opinion, concluding that E171 is safe for human consumption. The UK’s Food Standard Agency (FSA) reached the same conclusions earlier this year.
TiO2 in medicines in the EU
While the EFSA opinion only concerns TiO2 used in food, the European Commission stated in the Regulation adopted on 14 January 2022 that it will consult with the European Medicines Agency (EMA) and review the safety of TiO2 used in medications over the next three years.
Considering the growing scientific consensus over the safety of TiO2 in food, the TDMA calls on the European Commission to trigger a critical re-examination of the EFSA 2021 opinion. The conclusions of international scientific authorities should be duly taken into consideration in the EU assessment of TiO2’s safety and its continued use in pharmaceuticals.
How important is TiO2 in medicines?
In an opinion issued on 8 September 2021, the European Medicines Agency concluded that TiO2 cannot be replaced without a negative impact on the quality and quantity of medicines in the EU. The EMA opinion stresses that a requirement to replace TiO2 in medicines will almost certainly cause “significant medicines shortages” in the EU market, with “major implications for patients”.
The EMA points out that, because of the time and costs involved in the reformulation of a substantial volume of products, any requirement to replace TiO2 in medicines will almost certainly cause shortages but also withdrawals from the market of medicinal products. Products such as pediatric and orphan health maintenance (like blood pressure) medicines would be likely the most impacted due to the millions of people who rely on these drugs.
 European Medicines Agency (2021). Final feedback from European Medicine Agency to the EU Commission request to evaluate the impact of the removal of titanium dioxide from the list of authorised food additives on medicinal products, EMA/504010/2021, page 1 and 4.