Name: Titanium Dioxide
CAS No: Dioxotitanium [13463-67-7]
BP: Titanium Dioxide JP: Titanium Oxide PhEur: Titanium Dioxide USP: Titanium Dioxide
Anatase titanium dioxide; brookite titanium dioxide; color index number 77891; E171; Hombitan FF-Pharma; Kemira AFDC; Kronos 1171; pigment white 6; Pretiox AV-01-FG; rutile titanium dioxide; Tioxide; TiPure; titanic anhydride; titanii dioxidum; Tronox.
Dioxotitanium [13463-67-7]
TiO2 79.88
Titanium dioxide is widely used in confectionery, cosmetics, and foods, in the plastics industry, and in topical and oral pharmaceutical formulations as a white pigment. Owing to its high refractive index, titanium dioxide has lightscattering properties that may be exploited in its use as a white pigment and opacifier. The range of light that is scattered can be altered by varying the particle size of the titanium dioxide powder. For example, titanium dioxide with an average particle size of 230nm scatters visible light, while titanium dioxide with an average particle size of 60nm scatters ultraviolet light and reflects visible light.(1) In pharmaceutical formulations, titanium dioxide is used as a white pigment in film-coating suspensions,(2,3) sugar-coated tablets, and gelatin capsules. Titanium dioxide may also be admixed with other pigments. Titanium dioxide is also used in dermatological preparations and cosmetics, such as sunscreens.(1,4)
White, amorphous, odorless, and tasteless nonhygroscopic powder. Although the average particle size of titanium dioxide powder is less than 1 mm, commercial titanium dioxide generally occurs as aggregated particles of approximately 100 mm diameter. Titanium dioxide may occur in several different crystalline forms: rutile; anatase; and brookite. Of these, rutile and anatase are the only forms of commercial importance. Rutile is the more thermodynamically stable crystalline form, but anatase is the form most commonly used in pharmaceutical applications.
See Table I.
Density (bulk) 0.4–0.62 g/cm3 (5) Density (tapped) 0.625–0.830 g/cm3 (6) Density (true) 3.8–4.1 g/cm3 for anatase; 3.9 g/cm3 for Hombitan FF-Pharma; 3.9–4.2 g/cm3 for rutile. Dielectric constant 48 for anatase; 114 for rutile. Hardness (Mohs) 5–6 for anatase; 6–7 for rutile. See also Section 18. Melting point 18558C Moisture content 0.44% NIR spectra see Figure 1. Particle size distribution Average particle size = 1.05 mm;(5) 0.3 mm for Hombitan FF-Pharma. See also Figures 2 and 3. Refractive index 2.55 for anatase; 2.5 for Hombitan FF-Pharma; 2.76 for rutile. Specific heat 0.71 J/g (0.17 cal/g) for anatase; 0.71 J/g (0.17 cal/g) for rutile. Specific surface area 9.90–10.77m2/g; 10.0m2/g for Hombitan FF-Pharma. Solubility Practically insoluble in dilute sulfuric acid, hydrochloric acid, nitric acid, organic solvents, and water. Soluble in hydrofluoric acid and hot concentrated sulfuric acid. Solubility depends on previous heat treatment; prolonged heating produces a less-soluble material. Tinting strength (Reynolds) 1200–1300 for anatase; 1650–1900 for rutile.
Titanium dioxide is extremely stable at high temperatures. This is due to the strong bond between the tetravalent titanium ion and the bivalent oxygen ions. However, titanium dioxide can lose small, unweighable amounts of oxygen by interaction with radiant energy. This oxygen can easily recombine again as a part of a reversible photochemical reaction, particularly if there is no oxidizable material available. These small oxygen losses are important because they can cause significant changes in the optical and electrical properties of the pigment. Titanium dioxide should be stored in a well-closed container, protected from light, in a cool, dry place.
Owing to a photocatalytic effect, titanium dioxide may interact with certain active substances, e.g. famotidine.(7) Studies have shown that titanium dioxide monatonically degrades film mechanical properties and increases water vapor permeability of polyvinyl alcohol coatings when used as an inert filler and whitener.(6) Titanium dioxide has also been shown to induce photooxidation of unsaturated lipids.(8)
Titanium dioxide occurs naturally as the minerals rutile (tetragonal structure), anatase (tetragonal structure), and brookite (orthorhombic structure). Titanium dioxide may be prepared commercially by either the sulfate or chloride process. In the sulfate process a titanium containing ore, such as ilemenite, is digested in sulfuric acid. This step is followed by dissolving the sulfates in water, then precipitating the hydrous titanium dioxide using hydrolysis. Finally, the product is calcinated at high temperature. In the chloride process, the dry ore is chlorinated at high temperature to form titanium tetrachloride, which is subsequently oxidized to form titanium dioxide.
Titanium dioxide is widely used in foods and oral and topical pharmaceutical formulations. It is generally regarded as an essentially nonirritant and nontoxic excipient.
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection, gloves, and a dust mask are recommended. Titanium dioxide is regarded as a relatively innocuous nuisance dust,(9) that may be irritant to the respiratory tract. In the UK, the long-term (8-hour TWA) workplace exposure limit is 10 mg/m3 for total inhalable dust and 4 mg/m3 for respirable dust.(10) Titanium dioxide particles in the 500nm range have been reported to translocate to all major body organs after oral administration in the rat.(11)
Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (dental paste; intrauterine suppositories; ophthalmic preparations; oral capsules, suspensions, tablets; topical and transdermal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Coloring agents.
Titanium dioxide is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. Titanium dioxide is a hard, abrasive material. Coating suspensions containing titanium dioxide have been reported to cause abrasion and wear of a steel-coated pan surface, which led to white tablets being contaminated with black specks.(12) If titanium dioxide is used as a pigment in the EU, it should conform to the appropriate food standards specifications, which are more demanding than the pharmacopeial specifications. When mixed with methylcellulose, titanium dioxide can reduce the elongation and tensile strength of the film but slightly increase the adhesion between pigmented film and the tablet surface.(13) A specification for titanium dioxide is contained in the Food Chemicals Codex (FCC).(14) The EINECS number for titanium dioxide is 236-675-5. The PubChem Compound ID (CID) for titanium dioxide is 26042.