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

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.