Titanium dioxide (TiO2) is a white pigment that is widely used in many applications, including medicine. In pharmaceuticals and supplements, titanium dioxide is often added as an inactive ingredient to provide coloration. However, the exact color that titanium dioxide appears can vary depending on factors such as particle size, crystal structure, and interactions with other ingredients.
Uses of Titanium Dioxide in Medicine
Titanium dioxide has several uses in medicine and pharmaceuticals:
- As a white pigment coating for tablets and capsules
- To provide opaqueness in liquid medications
- As a thickening agent in topical ointments and creams
- As a white colorant in dental composites
- As a brightening agent in cosmetic products like sunscreens and whitening toothpastes
The inert and stable nature of titanium dioxide makes it ideal for these applications. It is considered a safe additive by the U.S. Food and Drug Administration (FDA) and other regulatory agencies.
Crystal Structures
Titanium dioxide can exist in three different crystal structures: anatase, rutile, and brookite. Rutile is the most common crystal form used in medicine:
- Rutile – This tetragonal crystal structure results in a white color. Rutile titanium dioxide reflects light efficiently, enhancing its opacity and brightness.
- Anatase – The anatase form has a lower refractive index, resulting in less opacity. It absorbs certain wavelengths of UV light.
- Brookite – This orthorhombic form is rare and unstable. It has optical properties between rutile and anatase.
Most pharmaceutical-grade titanium dioxide consists of the rutile crystal polymorph or a rutile-anatase mixture. The rutile form provides an optimal white pigment for use in tablets, capsules, and other medications.
Particle Size Effects
In addition to crystal structure, particle size also affects the coloration of titanium dioxide. Smaller particle sizes lead to a smoother texture and enhanced light scattering. General particle size ranges include:
- Fine particles – Around 0.1-0.3 microns. Result in a transparent appearance.
- Ultrafine particles – Under 0.1 microns. Absorb and scatter light, providing opacity.
- Micro-particles – Larger than 0.3 microns. Provide high whiteness and brightness.
Most pharmaceutical titanium dioxide consists of fine or ultrafine particles in the nano size range. The small size optimizes light scattering effects for an opaque, white appearance.
Color Variations
Although titanium dioxide pigments usually appear white, there can be subtle variations in color depending on several factors:
- Crystal structure – Anatase has a more bluish undertone, while rutile is a flat white.
- Particle size – Finer particles reflect light more uniformly for a brighter white color.
- Thickness of application – Heavy application results in a more chalky white, while thin applications look more translucent.
- Interactions with other ingredients – Certain excipients like iron oxides may alter the undertone.
- Manufacturing process – Impurities and coating processes affect whiteness.
While these factors can lead to subtle variations in color, the titanium dioxide used in pharmaceuticals and medicine is designed to provide a clean, bright white appearance in most applications.
Opacity and Light Absorption
In addition to its white color, titanium dioxide also provides opacity. The small particle size and high refractive index of TiO2 results in strong light scattering. This gives it the ability to block or mask the color of underlying medicinal ingredients.
However, titanium dioxide does not absorb light evenly across the visible spectrum. It absorbs certain ultraviolet (UV) wavelengths, leading to a UV absorption edge. This provides some UV shielding effects in sunscreens and other personal care products.
Safety Profile
Titanium dioxide has a low toxicity profile and is generally recognized as safe by regulatory bodies. Nano-sized particles less than 100 nm do undergo more scrutiny, but are still considered to have low risks in pharmaceutical use when properly formulated for stability.
Any potential health risks would depend on the extent of exposure. Titanium dioxide is insoluble and mostly inert. Systemic absorption is low when given orally or applied topically. TiO2 particles are not thought to penetrate through intact skin.
Overall, the colorant levels used in pharmaceuticals are very low and not considered toxic. But more long-term research is still needed on accumulation and nanotoxicity effects.
Conclusion
In summary, titanium dioxide is widely used as a white pigment additive in medicines due to its brightness, opacity, and safety profile. The most common crystal form used is rutile, which provides a clean white color when finely milled.
Subtle variations in color and opacity can arise based on crystal structure, particle size, application thickness, and interactions with other ingredients. But titanium dioxide is designed to maintain a consistent bright white appearance in pharmaceutical applications.
When used at typical low levels, titanium dioxide is considered relatively inert and safe. But the nano-sized particles may deserve more investigation for long-term toxicology and body accumulation.
Titanium dioxide provides an invaluable coloring function in medicine. But its use and safety will continue to be optimized as more research emerges on nanoparticle toxicology.
