Friday, July 23, 2021

Pharmaceutical Emulsions: An Overview

by | December 15, 2020 0

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.

Types of emulsion

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

  1. Oil-in-water (O/W) emulsion
  2. Water-in-oil (W/O) emulsion

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

  1. Water-in-oil-in-water (W1/O/W2) emulsion
  2. Oil-in-water-in-oil (O1/W/O2) emulsion.

By considering particle size, pharmaceutical emulsions can be

  1. Macroemulsions (droplets size usually exceeds 10 mm)
  2. Miniemulsions (droplets size usually 0.1–10 µm)
  3. Microemulsions (droplets size usually 100-600 nm)
  4. Nanoemulsions (droplets size usually below 100 nm)

Emulsions can also be classified based on the mode of administration into

  1. Oral emulsions e.g., castor oil, liquid paraffin
  2. External emulsions e.g., creams
  3. Parenteral emulsions e.g., vitamins
  4. Rectal emulsions e.g., enema.

Read Also: Understanding Pharmaceutical Liquid Dosage Forms

Theories of Emulsions

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

  1. surface tension theory
  2. oriented-wedge theory and
  3. interfacial film theory

Manufacturing of Pharmaceutical emulsions

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:

  1. continental, or dry gum, method
  2. English, or wet gum, method
  3. in situ soap method
  4. mechanical method

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:

  • Uniformity of surface coverage.
  • Monodispersed droplet sizes in the population produced.
  • The smallest droplet size possible.

Read Also: Liquid Dosage Forms: Pharmaceutical Suspensions

Tests for identification of emulsion types

  1. Dilution test
  2. Dye test
  3. Fluorescence test
  4. Conductivity test
  5. Cobalt chloride paper test

Stability of pharmaceutical emulsions

Emulsions must demonstrate physical, chemical, and microbial stability throughout their shelf life under recommended packaging and storage conditions.

a. Physical instability

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:

  1. flocculation
  2. creaming
  3. coalescence
  4. breaking

b. Chemical instability

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.

c. Microbial growth

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.

Pharmaceutical application of emulsions

  • Emulsions (macroemulsions and microemulsions) are generally well documented as carriers for hydrophilic and lipophilic drugs.
  • Oils and drugs having objectionable taste or texture can be made more palatable for oral administration by formulating into emulsions. As a result, mineral oil-based laxatives, oil-soluble vitamins, vegetable oils, high-fat nutritive preparations for enteral feeding, and certain drugs such as valproic acid are formulated frequently in an oil-in-water (o/w) emulsion form.
  • With topically applied emulsions, the formulation scientist can control the viscosity, appearance, and degree of greasiness of cosmetic and dermatologic products. o/w emulsions are most useful as water-washable bases, whereas water-in-oil (w/o) emulsions are used widely for the treatment of dry skin and emollient applications to provide an occlusive effect.
  • Semisolid preparations, such as ointments and creams, represent the dispersions of liquids in solids, which are used topically.
  • Emulsions are also employed in many other clinical applications as radiopaque emulsions and parenteral emulsions and in blood replacement therapy.

References

  • Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics: Basic Principles and Application to Pharmacy Practice. USA: Elsevier Inc.
  • Mahato, R. and Narang, A. (2018). Pharmaceutical Dosage Forms and Drug Delivery (3rd  ed.).New York: Taylor & Francis Group, LLC.
  • Sarker, D. (2013). Pharmaceutical Emulsions: A Drug Developer’s Toolbag. UK: John Wiley & Sons, Ltd.



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