The Need for Excipients

It is usually not possible to prepare a capsule, oral powder or tablet from an active substance without the addition of any excipients. Firstly, the volume of the active substance is often very small a diluent is necessary in order to handle the powder mixture. Secondly, the active substance may not have good flow properties these can be improved by addition of a glidant. Another reason to use excipients is that a preparation, consisting only of an active substance, may not disintegrate well in the gastro-intestinal tract a disintegrating agent can improve this. Many excipients combine a number of such functions so the number of different excipients can be limited and the potential interactions between materials can be minimised [12]. The next sections 

The intrinsic properties of the active substance are difficult to change, but the pharmacist can choose the right excipients and preparation techniques to overcome or decrease the impact of limitations. Although excipients should be pharmacologically inactive, they may cause adverse effects. The European Paediatric Formulation Initiative (EuPFI) project is considering the suitability of excipients for paediatric formulations. The results have been published in the STEP database [13]. For example many colouring agents have been associated with hypersensitivity and other adverse reactions. 

Solid oral dosage forms are preferably prepared with the active substance as such. The particle size of active substances in fast-release preparations should preferably be not larger than 180 pm to reach a compromise between dissolution rate and flowability. If the raw material consists of particles that are too large, the particles should be reduced in size (see Sect. 29.2). 

When the active substance is not available as raw material, tablets containing the active substance may be used, providing that both the tablet and the active substance are suitable for processing into a capsule. Sometimes the active substance is extracted by dissolution into a liquid but unfortunately these solutions (especially aqueous liquids) cannot be further used in the preparation of capsules because they affect the gelatine shell. However, there are exceptions such as macrogols of small chain lengths [14], which do not affect the gelatine. 

Highly soluble salts (for example sodium fluoride, potassium chloride, potassium citrate) are preferably not prepared in a capsule at all, since rapid dissolution can result in a high local concentration that may be harmful to the mucosa of the gastro-intestinal tract. An enteric coating on capsules and tablets can protect the gastric mucosa from irritating active substances. But the preparation of an oral solution of the active substance may be a better alternative. 

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