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Greater awareness and increasing popularity among consumers to select drugs or food supplements exhibiting a clean label is a trend that producers are unable to ignore. The demand for authentic products and total transparency is affecting the entire industry and IMA is well prepared to cater for this scenario as it matures. Caterina Funaro, Process R&D Laboratory Manager at the IMA Active laboratory explores...
The Clean Label Concept
So what is a clean label and what does it certify? Starting with dietary supplements, moving through nutritionals and on to cosmetic products, the clean label concept affirms the absence of any artificial or synthetic excipients. And this all begins as it impacts the suppliers of raw materials, and continues along the entire production process right up to final coating in the case of coated tablets.
Many raw material suppliers are now members of the Clean Label Alliance, an association helping companies producing dietary supplements by providing top-of-the-line resources and solutions to efficiently produce clean label products.
Driven by consumers, the clean label trend is gaining momentum and the market is moving away from ingredients that are not natural. One prime example is that of colouring agents that should no longer make use of titanium dioxide. Formulating an effective coating avoiding the use of titanium dioxide can be extremely challenging. Whereas TiO2 poses little or no adverse health risks if used in lotions and skin creams, if inhaled - as is possible when in powder form – it is considered a potential carcinogen by the International Agency for Research on Cancer.
The tablet-coating process relies heavily on titanium dioxide as an additive for its whitening and opacifying properties. Avoiding its use in aesthetic formulations will make effective tablet coverage more difficult. Many raw material suppliers are actually adapting their ready-to-use formulations in such a way as to avoid the use of titanium dioxide.
The best coverage is achieved by correctly managing key elements that are part of the formulation. This includes the type of opacifier used and its concentration, and the quantity of coating required per unit surface area to ensure optimum coverage of the initial cores. When using titanium dioxide-free formulations, an increase in weight is normally advisable to improve core appearance and stability to light. This gain ranges from 4-7% and depends on the cores and the need to contrast the yellowing effect.
Unfortunately, there are no concrete alternatives to TiO2 having identical opacifying properties, so it is all about finding the best combination of ingredients to obtain a great coating finish, as close as possible to achieving the appealing look of a titanium-based coating. Many ready-to-use coating formulations exist on the market. These are mainly HPMC-based, available as clear, white or pigmented systems.
Growing Initiatives to Replace Titanium Dioxide as an Excipient
European Food Safety Authority’s (EFSA) updated assessment on the safety of titanium dioxide as a food additive (published in summer 2021) concludes that concerns about the genotoxicity of TiO2 particles cannot be excluded. Furthermore, the European Commission issued Commission Regulation (EU) 2022/63 banning the use of titanium dioxide as a food additive (E171): this regulatory change particularly affects the food and dietary supplement industry.
Even though the pharmaceutical sector is not yet affected by this regulatory change, scientists are already moving forward and trying to reformulate tablet coatings to include titanium dioxide alternatives and in some cases even talc. In an aim to anticipate a potential trend, the IMA Active Laboratory has kicked off an important initiative whose aim is to acquire extensive experience with regard to new excipients in order to be ready with the best technical solutions.
Such an initiative is also in line with the group’s internal sustainability policy, the IMA Zero project, whereby everything is done to minimise the environmental impact of industrial manufacturing. This project drives solutions stretching from reduced power needs through selected materials, eco-friendly packaging solutions all the way up to minimal water consumption.
Calcium carbonate and sugars such as isomalt or rice starch are combined together to create equivalent opacity and good light stability. The solids concentration varies between 15-20% depending on raw material suppliers and the final weight gain depending on the substrate: for white tablets a 3-5 % weight gain would be sufficient. To ensure satisfactory protection against light, a 4-6% gain could be recommended and even 7% may be necessary for dark substrates needing adequate covering.
Table 1 reviews a selection of popular products already available on the market and their relevant suppliers.
Table 1: a selection of popular TF coatings available on the market.
To complete this review, a table indicating the coating parameter ranges suggested for the above-mentioned products is provided for both pilot and production-scale coaters.
General ranges are given as opposed to specific parameters in order to cover all the different suppliers’ proposals.
Table 2 parameter ranges for coating processes with TF coating formulations.
Note: the 6% weight gain is targeted to simulate a worst-case scenario (dark or coloured tablets) but for white tablets, a lower increase could also be valid.
Raw material suppliers have endeavoured to mimic the opacifying effect of titanium dioxide, and several articles have been written to explain the different options. The most frequently-cited excipient in available literature is calcium carbonate, used at a certain particle size, offering strong opacifying properties and giving tablets a white colouring.
In conclusion, this review also underlines the fact that talc has also come under examination for being a potential hazard and carcinogenic. Pharmaceutical companies are already acting to replace talc with different excipients that ensure similar anti-tacking properties.