introdction to emulsions

An emulsion is a thermodynamically unstable system consisting of at least two immiscible liquid phases, one of which is dispersed as globules in the other liquid phase.

  1. Suface Active Agents as Emulsifying Agents:

    The system is stabilized by the presence of an emulsifying agent. Either the dispersed phase or the continuous phase may range in consistency from that of a mobile liquid to a semisolid. Thus, emulsified systems range from lotions of relatively low viscosity to ointments and creams, which are semisolid in nature. The particle diameter of the dispersed phase generally extends from about 0.1 to 10 m m. although particle diameters as small as 0.01 m m and as large as 100 m m are not uncommon in some preparations.
  2. W/O and O/W Classification

    Invariably, one liquid phase in an emulsion is essentially polar (i.e. aqueous), while the other is relatively nonpolar (e.g. an oil) When the oil phase is dispersed as globules throughout an aqueous continuous phase, the system is referred to as an oil-in-water(o/w) emulsion (Fig 1a). When the oil phase serves as the continuous phase, the emulsion spoken of as a water in oil (w/o) emulsion (Fig 1b).

    Medicinal emulsions for oral administration are usually of the o/w type and require the use of an o/w emulsifying agent. These include synthetic nonionic surface-active agents, acacia, tragacanth, and gelatin. Not all emulsions that are consumed, however belong to the o/w type. Certain foods such as butter and some salad dressings are w/o emulsions.

    Externally applied emulsions may be o/w or w/o, the former employing the following emulsifiers in addition to the ones mentioned previously: sodium lauryl sulfate, triethanolamine stearate, monovalent soaps such as sodium oleate, and self-emulsifying glyceryl monostearate, ie glyceryl monostearate mixed with a small amount of a monovalent soap or an alkyl sulfate.

    Pharmaceutical w/o emulsions are used almost exclusively for external application and may contain one or several of the following emulsifiers: polyvalent soaps such as calcium palmitate, sorbitan esters (Spans), cholesterol and wool fat.

  3. Clinical Uses of Emulsions

    1. Oral (Liquid administration of oils, eg. Vitamins A, D, and E)

      Reasons of use:

      1. No oily mouth-feel (if an o/w emulsion is used).
      2. Better taste than if completely solubilized.
      3. May be more bioavailable.
      4. Solubilized drug may be more bioavailable
    2. Parenteral Drug Solubilization
      1. Emulsification of oils.
      2. Emulsification of lipids for parenteral nutrition.
    3. Topical
      1. O/W emulsions: Drug suspended or solubilized in the oil phase; less greasy than petrolatum type bases; no occlusion.
      2. W/O emulsions: some occlusive effect but slightly less greasy than the petrolatum bases.
  4. Mechanism of Emulsion Stabilizers

    Emulsions can be formed by mechanical means but it is generally easier if emulsifying agents are present. Unless stabilized, the dispersed phase will quickly coalesce.

    1. Surfactants (Figure 2a)

      Form monomolecular layers at interface of disperse and continuous phases. A monomolecular layer is formed on the surface of the dispersed phase. This layer:

      1. Reduces but does not eliminate the interfacial tension in the emulsion.
      2. For ionic surfactants in an O/W emulsion, a charged layer with associated counterion layer is formed around the oil droplet. The resulting electrical repulsion reduces the tendency to coalesce.
      3. For non-ionic surfactants, there can be repulsive effects in the bulk continuous phase due to interactions of the hydrophilic chains. In practice, emulsions are usually formulated using a mixture of materials to give maximum strength and flexibility to the protective layers or films.
    2. Hydrophilic colloids (protective colloids) (Figure 2b)

      Form multimolecular layers around droplets of the disperse phase.

      These materials are similar to surfactants since they tend to concentrate at the interface but unlike surfactants, they form multimolecular layers. Their primary function is to physcically block coalescence via film formation. A secondary function depends on their size and hydrophilicity. Since they are generally high molecular weight, water soluble polymers, they increase the viscosity of the continuous phase and reduce the mobility of the dispersed particles.

    3. Finely divided solids (Figure 2c)

      Form a particulate "film"around dispersed particles.

      These particles rely on adsorption to interfaces and like the hydrophilic colloids, function by forming a physical barrier to coalescence.

  5. Emulsion Coalescence

    Instability in a disperse system occurs when attractive force- between molecules in the individual phases exceed attractive forces between molecules in the opposite phases. To become more stable the system could theoretically:

    1. Reduce the contact between the two phases by reducing the volume of one or both – not feasible.
    2. Alter the forces between molecules in one or both phases - not feasible.
    3. Since surface area of the dispersed phased increases as particle size decreases, coalescence represents the only practical means of achieving stability.

    To get a rough idea of the areas involved, imagine 1 cm cube oil and 1 cm cube water. If these were in a square container with 1 cm sides, the contact area between oil and water would be 1 cm square.

    If the oil were to be dispersed into droplets of 10 nm diameter

    a. The volume of the mixture would remain 2 cm square.

    b. The intermolecular forces would remain the same.

    c. The contact area would increase from 1 cm square to 600 m square increase,

    (a 6,000,000 x increase).

    The oil droplets would quickly coalesce into the original two separate phases with the original contact area of 1 cm square.

    Thermodynamic driving force of coalescence is one of increasing entropy in the system. While a hydrophobic portion of a molecule is in an aqueous solution, water molecules align themselves in a manner so that the effective interaction between water and the hydrophobic molecule is minimized. This ordering obviously decreases the degree of disorder or randomness (ie, entropy) in the system. Removal of part or all of the lipophilic portion of the molecule from solution releases ordered water and produces an increase in randomness in the system, that is, an increase in entropy in the system. Free energy (G) in the system is related to the function:

    D G = D H - TD S

    Where DH is the heat of phase transfer, and T is the absolute temperature

    Change of free energy in the system (D G) is related to heat/phase transfer (D H), the absolute temperature and the change in entropy (D S). If D S is positive (ie, randomness is increased due to release of structured water), the term -TD S becomes more negative and the system reaches a more favourable energy level.

  6. Emulsion formulation considerations 

    Ingredient Class Considerations
    Oil   Type, percent of formulation
    Surfactant   Class, HLB
    Stabilizer Co-emulsifier Packing in film
      Viscosity modifier Solubility regarding o/w or w/o
      Co-emulsifier Incorporation into liquid, crystalline phase
      Coating agent Hydrophilic colloid, solid
    Preservative Microbiological Activity, partitioning
      Antioxidant Solubility and partitioning

    Other Specific Aspects

    1. Structuring of the continuous phase A mixture of the surfactants can form laminar structures at higher concentrations. the regular packing in these structure approximate the order seen in solid crystals so they may be referred to as "liquid crystals". Some co-emulsifiers may dissolve to some degree in the oil phase of the emulsion during its preparation but, upon cooling, they begin to diffuse out. Since they are even less water soluble, they may diffuse into these liquid crystals. Since many are waxy at room temperature, they will become more rigid resulting in the formation of a firm structure throughout the continuous phase.
    2. Palatibility of oral emulsions Due to the soap-like nature of most of the synthetic surfactants, they may be unsuitable for use in oral or parenteral emulsions. Natural surfactants like the phospholipids and phosphatides may be more appropriate in these cases. The best example of such materials are the lecithins.