Coloring agents

colourants; colours; dyes; lakes; pigments; FD&C and D&C colours; examples: tartrazine (E102), quinoline yellow (E104), sunset yellow FCF (E110), erythrosine (E127), indigo carmine (E132), titanium dioxide (E171), iron oxides (E172)

Various: synthetic water-soluble dyes, aluminium lakes, inorganic pigments and natural colours · [—]

Polymer, mixture or material of variable composition — no single molecular formula applies.

Colouring agent

Typical concentrations: — · Dosage forms: Solid, Liquid, Semi-solid

Added to tablets, film and sugar coatings, hard and soft capsule shells, oral liquids and topical products to make the product easier to identify, to distinguish strengths, to mask uneven appearance and to improve patient acceptance. Opaque pigments such as titanium dioxide and iron oxides also protect light-sensitive drugs. Colours are effective at very low levels, usually well under 1% of the dosage form; pigments and lakes make up a larger share of the solids in coating formulations.

Pharmaceutical colours fall into four groups: water-soluble synthetic dyes (mostly azo, triphenylmethane, xanthene and quinoline dyes), aluminium lakes (a dye adsorbed on hydrated alumina, giving an insoluble pigment), inorganic pigments (titanium dioxide, iron oxides) and natural colours (for example carotenoids, curcumin, riboflavin, chlorophylls, beetroot red and caramel).

Water-soluble dyes

colour by dissolving; used in solutions and wet granulation; prone to migration and mottling

Aluminium lakes

insoluble; colour by dispersion; more stable to light and heat than the parent dye; preferred in film coatings and suspensions; may bleed at strongly acidic or alkaline pH

Inorganic pigments

insoluble, opaque and very stable to light (iron oxides give red, yellow and black shades; titanium dioxide gives white opacity)

Natural colours

generally less stable to light, heat, pH and oxidation than synthetic colours

Many dyes and most natural colours fade on exposure to light, and fading can also be caused by heat, extremes of pH, oxidising or reducing agents and trace metals. Store in well-closed containers protected from light; colour stability in the finished product should be checked under ICH photostability conditions.

Azo dyes can be decolourised by reducing agents such as ascorbic acid and by some sugars and metal ions; erythrosine precipitates in acidic solutions; anionic dyes may interact with cationic drugs or surfactants. Lakes dissolve and release dye outside a roughly neutral pH range.

Synthetic dyes are made by organic synthesis from aromatic intermediates and purified to strict limits for heavy metals and subsidiary colours. Lakes are produced by precipitating a dye onto a freshly prepared alumina hydrate substrate. Iron oxides are mostly synthetic, while natural colours are extracted from plant, algal or insect sources.

Most approved colours are of low toxicity at the levels used. Tartrazine and some other azo dyes can cause hypersensitivity reactions such as urticaria and asthma, particularly in aspirin-sensitive people, and some azo colours have been associated with hyperactivity in children, so EU foods containing them carry a warning. Titanium dioxide is no longer authorised as a food additive in the EU since 2022 because EFSA could not exclude genotoxicity, although it remains in use in medicines while alternatives are assessed.

Observe normal precautions for the quantity handled. Avoid dust: many colours stain skin and surfaces, and fine powders may irritate the eyes and respiratory tract. Wear gloves, eye protection and a dust mask.

Only listed colours may be used. In the USA, colours for drugs must be listed in 21 CFR Parts 73 and 74, and FD&C and D&C colours are batch-certified by the FDA. In the EU, colours in medicines are limited to those authorised as food colours (E-numbers) under Directive 2009/35/EC, with purity criteria set by food-additive legislation.

Iron oxides; titanium dioxide; individual dyes and lakes such as sunset yellow FCF, tartrazine, quinoline yellow, indigo carmine and erythrosine; caramel; riboflavin.

Permitted colours differ between countries, so a colour acceptable in one market may need replacing for another; check the target market's list early in development. Water-soluble dyes migrate to the granule surface during drying of wet granulations and cause mottling, which is why lakes or pigments dispersed in a film coat give more uniform colour.