Do we need to replace Titanium Dioxide in Pharmaceutical Formulations?
Titanium dioxide has been under discussion for some time now. In 2019, France made the decision to completely ban TiO2 in the nutraceutical sector from January 1, 2020. Now, the EFSA panel concluded, that E171 (TiO2) can no longer be considered as safe when used as a food additive in Europe. Besides its use in the food industry, TiO2 is also used in many pharmaceutical formulations, e.g. mainly in coatings and in hard capsules for opacity. For this reason we decided to do a small first LinkedIn Poll regarding the future of TiO2 in the pharmaceutical sector. We got very interesting results with a certain direction, and several detailed industry expert comments:
As you can see, nearly two hundred excipients industry specialists participated in our small poll. Most of the respondents (68%) think that TiO2 or the ban of TiO2 will become a very important topic in the pharmaceutical sector, already in a short time. Another 21% think it will become a very relevant topic, but in a few years. Nevertheless, there are 11% of industry specialists that have the opinion that it is not relevant at all.
In addition to the poll participation, we were sent comments and assessments from many different excipient experts and companies, which we want to give an overview of below.
One expert noted that many companies are already reformulating their products without TiO2. Due to the current safety concerns, this has been occurring more recently for several projects of his company. Even before that, many products were manufactured without TiO2 at the specific request of customers according to this poll participant. Especially in the nutraceutical sector, reformulations of products without TiO2 are increasing, and the EFSA decision reinforced this trend.
However there were also commentators that pointed out that it is difficult to say whether TiO2 should really be banned in the pharmaceutical sector. After all, according to their opinion titanium dioxide is a very important ingredient in thousands of today’s formulations, e.g. as a coating ingredient or to ensure the opacity of hard capsules.
If existing pharmaceutical product formulations are changed, these reformulated products would in turn have to be re-validated and re-verified for all possible properties because of variation submissions. According to another expert, it is questionable whether the responsible authorities can do this with this volume of products without bottlenecks (elsewhere).
On the other hand, one expert argued that TiO2 can be replaced quite “easily” by calcium carbonates or magnesium oxides. A visual difference is not visible to the naked eye anyway in the opinion of the commentator.
Another poll participant raised the question, if titanium dioxide should now really be banned, how to deal with other products regarding possible nanoparticles. He named excipients like magnesium stearate, silicon oxide or microcrystalline cellulose, which are also in discussion. If they would also be banned in a similar process, the pharmaceutical industry could face major difficulties.
The topic of the necessity of a full ban of TiO2 in pharmaceutical formulations remains controversial, even a majority of our poll participants think the developments go in this direction in a relatively short time. So the topic will be with us for the near future. It will be interesting to see how the regulating authorities in the various countries go forward here. Depending on their decisions and the regulatory framework, the pharmaceutical industry will be faced with major challenges.