Pharmaceutical emulsions are liquid disperse systems in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible. In emulsion terminology, the dispersed phase is the discontinuous or internal phase, and the dispersion medium is the continuous or external phase.
The diameter of the dispersed phase globules is generally in the range of about 0.1 to 10 μm, although it can be as small as 0.01 μm or as large as 100 μm. Emulsions are thermodynamically unstable and are usually stabilized by the presence of an emulsifier. The process of formation of an emulsion is termed emulsification.
Emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are semisolid in nature. Pharmaceutical emulsions are used for the administration of nutrients, drugs, and diagnostic agents. Topical creams and lotions are popular forms of emulsions for external use.
Emulsions typically consist of a polar (e.g., aqueous) and a relatively nonpolar (e.g., an oil) liquid phase. The two basic types of emulsions are
However, depending upon the need, more complex systems referred to as “double emulsions” or “multiple emulsions” can be made. These emulsions have an emulsion as the dispersed phase in a continuous phase and they can be either
By considering particle size, pharmaceutical emulsions can be
Emulsions can also be classified based on the mode of administration into
Several theories have been proposed to explain the stability of emulsions. Some of the theories are related to the functional role of emulsifiers and others to processing conditions. The most important theories are the
Emulsions may be prepared by using different methods, depending on the nature of the emulsion components and instrumentation available for use. On a small scale, as in the laboratory or pharmacy, emulsions may be prepared using equipment such as a porcelain mortar and pestle, mechanical blenders, and homogenizers.
In small-scale extemporaneous preparation of emulsions, four methods may be used:
On a large scale, injectable and ophthalmic emulsions are manufactured using the mechanical method in aseptic conditions.
The manufacture of an emulsion must be undertaken in a predictable and controlled manner, in order to obtain:
Emulsions must demonstrate physical, chemical, and microbial stability throughout their shelf life under recommended packaging and storage conditions.
Physical stability of an emulsion is characterized by the maintenance of elegance with respect to appearance, odor, color, taste, opacity, and viscosity. Four major phenomena are associated with the physical instability of emulsions:
The drug substance must be chemically stable in the dosage form throughout the shelf life of the product under recommended packaging and storage conditions in terms of both potency and impurities. The drug product must meet predetermined requirements of minimum potency of the drug substance and maximum levels of known and unknown impurities.
Factors governing the reaction kinetics of the drug substance, such as the reactivity of functional groups and the kinetics of reactions are no different for emulsion dosage forms than other solution-based dosage forms. Nevertheless, separation of the reacting species in the oily and aqueous phases can minimize reactivity and improve stability of a drug in an emulsion.
Microbial load of a dosage form must be controlled within the compendial and the regulatory levels. In addition to the health risks of microbial growth, microorganisms in an emulsion can cause physical separation of the phases.
Preservatives must be added in adequate concentrations in the formulations to resist microbial growth. The preservative should be concentrated in the aqueous phase because bacterial growth will normally occur there. The oil and water partition coefficient of the preservatives should be considered to calculate the concentration of the surfactant in the aqueous phase, which needs to be above the antimicrobial concentration.
The parabens (methylparaben, propylparaben, and butylparaben) are the commonly used preservatives in emulsions.