The colouration of tablets and capsules

Paul Smith from Sensient Pharmaceutical Technologies discusses the use of colour in solid oral dosage forms

Paul Smith from Sensient Pharmaceutical Technologies discusses the use of colour in solid oral dosage forms

Solid oral dosage forms, including tablets and gelatine capsules, represent approximately 80% of all pharmaceutical preparations. These types of dosage forms dominate the marketplace because they deliver a constant controlled dosage of active drug, have excellent stability properties, are easily stored, are convenient to use and are available in a range of physical appearances.

The shape, size and colour are all visual characteristics used to differentiate products, and the colouration of solid dosage forms is widespread, depending upon the physical properties of the product, the characteristics of the active ingredient and the geographic region in which the product is to be marketed.

There are a number of reasons to colour tablets, including:

•Identification. To help pharmacists and patients on multi-dosage regimes. A patient will often refer to the colour and shape of dosage form (e.g. 'the little blue tablet for my heartburn') rather than the generic nomenclature and dosage level of the tablet;

•Flavour perception. The patient's expectation of the flavour and colour of a product is important; for example, consumers expect a cherry flavoured lozenge to be red;

•Brand identification. Colour offers the pharmaceutical manufacturer an easy route to brand identification in a highly competitive market;

•Quality perception. Colour can be added to increase the aesthetic value of the product, thereby increasing the perception of quality;

•Counterfeit prevention. The development of unique colours for a particular active drug and the application of coloured printing can help to reduce the risk of counterfeiting.

Tablets can be coloured using three different approaches:

•Uncoated tablets can be coloured by the addition of insoluble pigments to the tablet base, thereby masking the natural colour of the active ingredient and/or other excipients which may be unattractive to the patient. Iron oxides are commonly used for this purpose.

•Sugar coating is considered to be the traditional method for coating tablets. The technique was developed in the late 19th century by the confectionery industry, and the main advantage of this type of coating is that it produces elegant and attractive coated pieces with a high gloss appearance. It is, however, a time-consuming process, taking up to five days to complete, and requires a high level of skill to carry out successfully.

•The third approach is to use film coating. Forming the largest sector of the tablet colouring market, the global pharmaceutical industry is increasingly moving to adopt film coating techniques in order to reduce processing times, control coating characteristics and provide innovation. Film coating involves the deposition of a thin polymer-based film onto the tablet core, usually by a spray method. It has the added advantage that logos and brand names can be punched onto the tablet core, and these intagliations are clearly visible following coating.

There are three main components of a film coating system. These are the polymer (or 'film-former', most commonly cellulose derived materials such as hypromellose); a plasticiser (such as polyethylene glycols and propylene glycol, included to increase film flexibility); and the pigments, which are described below.

The most convenient to use and effective film coating products are a complete package of all three components, presented in a dry, granular

format. Such formulations provide a single ingredient for hydration into water, offering a complete film coat system for direct spraying onto the tablet bed. An example of this type of film coating product is Spectrablend from Sensient Pharmaceutical Technologies.

Pharmaceutical colorants can be classified as water-soluble dyes or water-insoluble pigments.

Dyes are water-soluble chemical compounds that exhibit their colouring power when dissolved in a solvent. They appear coloured by selectively absorbing specific wavelengths of light and allowing the remaining balance of wavelengths to be transmitted.

There are several chemical classes of synthetic dyes and these are summarised in Table 1.

A popular alternative to synthetic dyes are natural colorants. These are obtained from animal, vegetable or mineral sources, or are synthetic duplicates of naturally occurring compounds. Table 2 lists some examples.

Pigments are water-insoluble colorants which colour by dispersion. They function by selectively absorbing some wavelengths of light and reflecting others; this change in the proportion of wavelengths is perceived as colour. Insoluble pigments were originally available only as naturally occurring inorganic compounds such as titanium dioxide, iron oxides and ultramarine. Then approximately 50 years ago the concept of synthetic insoluble colorants - lake pigments - was developed. These are manufactured by precipitating and adsorbing water-soluble dyes onto an insoluble substrate, usually alumina hydrate. This chemical adhesion of the dye material onto the surface of the substrate renders the colorant insoluble. This insolubility prevents the colouring material from migrating, hence avoiding the most common problem associated with dyes in tablet coating applications.

The effect of particle size is critically important with lake pigments, since such materials produce colour by the reflection of light from their surface area. Thus the larger the surface area (i.e. the smaller the particle size), the more colour is perceived.

physical properties

Dyes and lake pigments differ in many respects, some of which are summarised in Table 3.

The relative stability of selected dyes and pigments is very important when formulating with colorants (stability refers to the relative length of time a colorant remains chemically and physically unchanged). Factors that affect colour stability include light, oxidising and reducing agents, heat, pH, microbial contamination and solubility limits. In general natural, colorants are not as stable as their synthetic counterparts.

An invaluable global resource for colour is the Colour Index (CI). This continually updated reference book is edited jointly by the Society of Dyers and Colourists (SDC) and the American Association of Textile Chemists & Colorists (AATCC). It lists more than 40,000 colorants, and provides information about practically every dye and pigment in commercial use. Its great benefit is that once the CI number of a colorant is known, its identity, chemical structure, chemical and physical properties, and more, are available.

controlled regulations

In the highly regulated pharmaceutical industry, the application of colorants is tightly controlled. In the US the use of colour in pharmaceutical products is strictly regulated by the Food and Drug Administration (FDA) via the relevant sections of the Code of Federal Regulations (CFR).

Within Europe the EC food legislation directive 95/45/EC has been adopted as the official documentation detailing the permitted colouring materials in pharmaceuticals. For other markets of the world, official guidelines are provided by the relevant legislative bodies.

Companies