Introduction to surface active agents (saa)

I. At the Interface:

Unlike forces between molecules in the bulk of a liquid phase, cohesive force formed by a molecule at an interface are between adjacent molecules and molecules in the bulk. Any cohesive forces between a molecule at an interface and molecules in the other phase are likely to be weak. The net effect is the formation of an overall inward force which tends to shrink the surface. This shrinkage of the surface can be regarded as an attempt to reduce or eliminate contact with the other phase. On the other hand, as the degree of interaction between molecules of one phase with molecules of another phase increases, the tendency to reduce contact decreases. In the case of the two liquid phases, reductions in shrinkage, i.e. increasing cohesive forces, may result in miscibility of the liquids.

A class of compounds known as surface active agents or surfactants contain both hydrophilic and lipophilic regions has an affinity for interfaces. They are molecules and ions that are adsorbed at interfaces. An alternative expression is amphilphile which suggests that the molecule or ion has a certain affinity for both polar and nonpolar solvents. Refer to figure 1, glyceryl monstearate, for an example of a surface active agent. Such a compound is an amphiphile which

  • is soluble in at least one phase of the system
  • forms monolayers at an interface
  • exhibits equilibrium concentrations at interfaces higher than the concentrations in the bulk solution and forms micelles at specific concentrations.
  • exhibits one or more of the following characteristics: detergency, foaming, wetting, emulsifying, solubilizing, dispersing.

Depending on the number and nature of the polar and nonpolar groups present, the amphiphile may be predominantly hydrophilic (water-loving), lipophilic (oil-loving), or reasonably well balanced between these two extremes.

Eg, straight-chain alcohols, amines, and acids are amphiphiles that change from being predominantly hydrophilic to lipophilic as the number of carbon atoms in the alkyl chains is increased. Ethyl alcohol is miscible with water in all proportions. In comparison, the aqueous solubility of amyl alcohol is much reduced, while cetyl alcohol may be said to be strongly lipophilic and insoluble in water.

Fig 1. Glyceryl monostearate

In order for the amphiphile to be concentrated at the interface, it must be balanced with the proper amount of water- and oil- soluble groups. If the molecule is too hydrophilic, it remains within the body of the aqueous phase and exerts no effect at the interface. Likewise, if it is too lipophilic, it dissolves completely in the oil phase and little appears at the interface.

II. Chemical Classification of Surface Active Agents

Surfactants may be viewed as providing a link between phases of markedly different polarities. Furthermore, the relationship of hydrophilic and lipophilic portions of the molecules will determine the overall characteristics of the compounds. This relationship has been numerically defined using the HLB (Hydrophile/lipophile balance). This provides a relative ranking of affiniites of amphiphiles towards aqueous and lipid solvent phases.

III. Systems of Hydrophile-Lipophile Classification

The Hydrophilic-Lipophilic balance (HLB) establishes a range of optimum efficiency for each class of surfactant. The higher the HLB of an agent, the more hydrophilic it is. The Spans, sorbitan esters are lipophilic (low HLB values ranging from 1.8 - 8.6); the Tweens, polyoxyethylene derivatives of the Spans, are hydrophilic and have high HLB values, ranging from 9.6 - 16.7.

  • If the molecule is too hydrophilic, it remains within the aqueous phase and exerts no effect at the interface. Likewise, if it is too lipophilic it dissolves completely in the oil phase and little appears at the interface.
  • Depending on the number and nature of the polar and nonpolar groups present, the amphiphile may be predominantly hydrophilic to lipophilic as the number of carbon atoms in the alkyl chains is increased.

IV. Purity of SAA

Commercial SAAs are not single pure compounds, but contain a mixture of homologues of differing alkyl chain length because of

  1. Nature of raw starting materials e.g. petroleum fractions or natural fats
  2. Deliberate choice to achieve definite objectives
    e.g. cationic SAA: long chain compounds - bactericidal action; short chain homologues - solubilize the long chain molecules.

V. Pharmaceutical uses of SAA

  1. SAA used in emulsions as an emulsifying agent
  2. SAA used in suspensions as a flocculating agent
  3. SAA as a wetting agent
  4. SAA as a bactericidal agent
  5. SAA as a solubilizing agent
  6. To modify the properties of membranes
    • Enhancement of percutaneous absorption
    • Enhancement of transport across mucosal membranes (rectal, vaginal, ophthalmic, nasal)

  7. SAA as a foaming agent
  8. Many solutions containing surface active materials produce stable foams when mixed intimately with air. A foam is a relatively stable structure consisting of air pockets enclosed within thin films of liquid, the gas-in-liquid dispersion being stabilized by a foaming agent. The foam dissipates as the liquid drains away from the area surrounding the air globules, and the film finally collapses. Antifoaming agents such as alcohol, ether, castor oil, and some surfactants may be used to break the foam. Foams are sometimes useful in pharmacy but are usually a nuisance and are prevented or destroyed when possible. The undesirable foaming of solubilized liquid preparations poses a problem in formulation.