1. Overview of Titanium Dioxide

Owing to its high refractive index, titanium dioxide has light-scattering properties that can be used as a white pigment and opacifier, and is widely used in solid oral dosage preparations (such as tablets, soft capsules, hard capsules, granules or powders for oral solutions and suspensions), oral semi-solid preparations (such as oral ointments, oral gels). Titanium dioxide can be found in many essential medicines for humans, including anti-diabetes drugs, antibiotics and some veterinary drugs. It is also present in other preparations other than oral ones, such as products for skin, inhalation (capsules), sublingual, transdermal and vaginal uses. 

2. Regulatory Status

EFSA announced that titanium dioxide may be genotoxic on Oct 26, 2021. Titanium dioxide is prohibited in foods. Currently the European Union has classified some forms of titanium dioxide as suspected inhalation carcinogens II.

The European Commission adopted Commission Regulation (EU) 2022/63 on Jan 14, 2022. Accordingly, since Feb 7, 2022, the use of titanium dioxide as a food additive in all foods, including dietary supplements is prohibited. To reduce the potential impact of the Regulation on food operators, a six-month transition period is provided, where foods produced with titanium dioxide may continue to be placed on the market until Aug 7, 2022. After that date, food products may remain on the market until their date of minimum durability or ‘use by’ date. Meanwhile, the European Commission will review the use of titanium dioxide in medicinal products within three years after the date of entering into force of the Regulation.

According to the Handbook of Pharmaceutical Excipients, owing to a photocatalytic effect, titanium dioxide may interact with certain active substances. Studies have shown that titanium dioxide monatonically degrades film mechanical properties and increases water vapor permeability of polyvinyl alcohol coatings when used as an inert filler and whitener. Titanium dioxide can also cause photooxidation of unsaturated fatty acids.

3.Lefancaps® TiO2-free Solutions

In order to meet the growing demands of the customers and new titanium dioxide-free requirements for foods in the European Union, Lefancaps® has launched a series of empty capsule solutions that do not contain titanium dioxide but still with the effect of light blocking, including empty gelatin capsules, vacant hypromellose capsules and vacant pullulan capsules.

3.1 Alternative Solution with Iron Oxides

As inorganic colorants, iron oxides are becoming of increasing importance. It was assessed by the US Food and Drug Administration in 2017 that the use of synthetic iron oxide in tablet and capsule dietary supplements does not affect human health, or require an environmental assessment or environmental impact statement. GRAS listed. Included in 21CFR §186.1300. According to the Handbook of Pharmaceutical Excipients, iron oxides used for oral preparations can be up to 95.4mg.

With professional color matching personnels and color matching control system, Lefancaps® has launched the coloring series of iron oxides to meet the different needs of customers.

3.2 Alternative Solution with Crystalized Salt

With the technical breakthroughs of professional technical team, Lefancaps® alternative solution with crystalized salt provides the capsules in white color with light-blocking effect.

The crystalized salt is a tiny white powder, which can be used in the European Union, the United States, China and other regions. The addition limit is relatively high. Moreover, the light-blocking effect can be customized based on the needs of individual customers.

A partial result of the application is shown as below.