Particle size determination of sunscreens formulated with various forms of titanium dioxide

Background: There has been some apprehension expressed in the scientific literature that nanometersized titanium dioxide (TiO2) and other nanoparticles, if able to penetrate the skin, may cause cytotoxicity. In light of a lack of data regarding dermal penetration of titanium dioxide from sunscreen formulations, the Food and Drug Administration Center for Drug Evaluation and Research initiated a study in collaboration with the National Center for Toxicology Research using minipigs to determine whether nanoscale TiO2 in sunscreen products can penetrate intact skin. Four sunscreen products were manufactured. Method: The particle size distribution of three TiO2 raw materials, a sunscreen blank (no TiO2) and three sunscreen formulations containing uncoated nanometer-sized TiO2, coated nanometer-sized TiO2 or sub-micron TiO2 were analyzed using scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), and X-ray diffraction (XRD) to determine whether the formulation process caused a change in the size distributions (e. g., agglomeration or deagglomeration) of the TiO2. Results: SEM and XRD of the formulated sunscreens containing nanometer TiO2 show the TiO2 particles to have the same size as that observed for the raw materials. This suggests that the formulation process did not affect the size or shape of the TiO2 particles. Conclusion: Because of the resolution limit of optical microscopy, nanoparticles could not be accurately sized using LSCM, which allows for detection but not sizing of the particles. LSCM allows observation of dispersion profiles throughout the sample; therefore, LSCM can be used to verify that results observed from SEM experiments are not solely surface effects.