In order to bring about coacervation-phase separation, a number of processes have been employed. These have been developed and are being improved in order to meet the many requirements of producing microcapsules or microspheres with appropriate characteristics. Some of the factors which must be considered in the process include:

• Solubility of the polymer

• Solubility of the drug

• Heat stability of drug and polymer

• Proper size range of microcapsules or product

• Formation of coacervate or concentrated polymer solution with suitable characteristics such as appropriate viscosity, deposition onto and adherence to the core

• Appropriate shape characteristics

• Sensitivity of enzymes, biological products or drugs to the process

As a result of the characteristics of the polymer, the properties of the core and the desired features of the final product, which is usually microcapsules or microspheres, a number of processes have been developed to effect coacervation-phase separation. The following discussion is an attempt to organize the various processes and is based on the solubility of the polymer, the number of polymers which are expected to form the coating material and the type of process used in the procedure.

Polymer solubility. The solvent used to dissolve the polymer is water or an organic liquid. In order for coacervation-phase separation to take place, it is first necessary to dissolve the polymer in an appropriate solvent so that it can be induced to separate in a more viscous, but still fluid state, in order that it can surround or mix with the core and then be hardened. While most polymers are either soluble in water, such as gelatin, or in an organic solvent, e.g. ethyl acetate, such as ethylcellulose, some polymers, e.g. cellulose acetate phthalate, are soluble in acetone and also in alkaline water.

Number of polymers. In aqueous systems one or two water-soluble polymers are frequently used to form the polymer wall or matrix of the product. Usually, only a single polymer is used to form the wall or the matrix of the microcapsule when the polymer is soluble in the organic liquid. The intentional incorporation of two organic soluble polymers within the same coat or matrix of the microcapsules is infrequent.

It should be noted that polymers may also be used to induce coacervation-phase separation, to improve the process such as minimizing aggregation, or to stabilize an emulsion during the formation of microcapsules, but not be incorporated into the microcapsule coat. Polymers may also be used to gel the interior, that is the core, of liquid-filled microcapsules (Kondo, 1979a).

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