Study findings indicate an alternative coating that would comply with potential future regulation against use of titanium dioxide as a pharmaceutical excipient.
A novel high-performance liquid chromatography (HPLC) method could detect impurities in titanium dioxide (TiO2)-free coated drotaverine hydrochloride tablets, research suggests.
The approach could be applied for drug product purity testing, based on successful assessment by Strozik et al. of the commonly-used small molecule, spasmolytic drug drotaverine.
In 2022, the European Commission banned TiO2 as a food additive, a move that’s anticipated to be extended to pharmaceutical coatings.
“With over 90,000 drug products registered in the EU”, expansion of the regulation “would necessitate extensive efforts to reformulate and adapt already marketed drugs”, according to Strozik et al.
To support future regulatory compliance and development of coating alternatives, the authors conducted a six-month stability study. The long-term, intermediate and accelerated conditions identified an unknown impurity that exceeded the 0.2 percent threshold set by ICH Q3B(R2), later identified as perparaldine.
The authors proposed extending the reporting and qualification threshold for this impurity to 0.5 percent “ensuring acceptable product quality over at least a two-year shelf life”.
The paper highlighted research by Kawakita et al, which observed “that even low concentrations of red or yellow iron oxides provide substantial photoprotection, supporting the use of TiO2-free beige coatings as a viable alternative without compromising the chemical stability of the API”.
Results from the stability study showed drotaveraldine as the main degradation product of drotaverine, “detected at 0.3 percent, well below the 0.5 percent limit for known impurities”.
TiO2 can be successfully replaced by iron oxides in the film coating without adversely affecting the product stability”
As such, this indicates that TiO2 “can be successfully replaced by iron oxides in the film coating without adversely affecting the product stability”, suggesting potential application in pilot-scale manufacturing, according to Strozik et al.
Strozik et al. found that the impurity profile of formulation of the TiO2-free coated tablet was comparable to that of the TiO2-containing formulation.
This research was published in the International Journal of Applied Pharmaceutics.
