Using response surface methodology to quantify iron oxide levels needed to protect photolabile active pharmaceutical ingredients in oral solid dosage forms

Abstract

Titanium dioxide (TiO₂) is a commonly used excipient in pharmaceutical products. It functions as a pigment and opacifier in film coatings, providing photoprotection and enabling consistent product appearance for oral solid dosage forms. TiO₂ was banned in foods by the European Commission in 2022 and the decision on a ban in medicines will be revisited in early 2025. There is an urgent need to identify TiO₂ alternatives. Currently, no single excipient has been found to directly replace TiO₂ in existing film-coating systems. Iron oxide pigmentation offers a potential solution for addressing the role TiO₂ plays in photoprotection. Using a mixture model design of experiments (DOE), three iron oxides – red, yellow, and black – were assessed on their efficacy in photoprotection. A model photolabile active pharmaceutical ingredient (API) was prepared into tablets and coated with varied iron oxide concentrations in a PVA-based titanium dioxide-free (TF) film-coating. Red and yellow iron oxide were found to significantly reduce total photodegradation products. By including 1–1.5 % red or yellow iron oxide in this TF film-coating, 75–85 % photoprotection was achieved, while 2 % or greater red iron oxide had nearly complete photoprotection. A second photolabile API was tested to confirm the results of the DOE.