The combination of substances can be carried out by mixing or kneading. The basis for the dosage of different active substances is either a process of grinding and mixing (homogenization) or a dissolution and aggregation process (sieving). In some cases, both procedures are combined (e.g. dissolving salicylic acid in ethanol and sieving this solution through glass wool).
Chemical mixing of powders is carried out by intensively shaking or stirring the components together while spraying. Sometimes this process is done on a special mixer (e.g. Turbula) so that at least some of the fine particles are separated, but the solution is not yet clear. The product of this process is called coarse powder (granular solid), if it already exists as granules or fine powder when spraying has been possible. Mill mixing is a special case when only small quantities are to be mixed and mainly large crystals have to be split into smaller ones or finely divided solids.
If the ingredients are porous (e.g. low-density solids), they absorb moisture from the air and may clump together, unless particular precautions are taken (dehumidifying or humidifying of compressed air). Soluble components with different pH values can also interact chemically with each other if not matched in advance. High temperatures (e.g. in powder coating bake-out furnaces) can result in chemical reactions between compounds, which may also change the efficacy of the product (e.g. batch baking batch).
Chemical mixing involves handling both physical and chemical properties of substances with different osmotic pressure, density, viscosity, reactivity and solubility.
Physical properties may be of importance when mixing of substances is carried out in containers with limited room for stirring, e.g. by hydrodynamic shear forces of spinning blades, which can readily deform soft solids. Chemical properties are important when mixtures that are not compatible with each other have to be combined, e.g. when a neutralization reaction takes place, resulting in the formation of a precipitate.
Chemical reactions during mixing may result in changes to the activity or efficacy of active substances and their degradation products, which therefore should be considered in advance (e.g., by chemical simulation). The release profile can also be changed by chemically reacting drugs (e.g., esterases).
Mixing is usually carried out by kneading, although some media may also be sprayed (cooled) or stirred (heated), as appropriate. Mixing can take place manually or by machine (Mixer, Shaker). There are different mixer types for this purpose: planetary mixers, cylindrical mixers, flat or horizontal mixers, V-shaped or U-shaped mixers and ribbon or propeller mixers.
