Surfactants

Physical Pharmacy
 Surfactants
Solutes or molecules that are preferentially absorbed at the surface
or interface of liquids reduces the surface/interfacial tension.
Common examples from our routine life are soap, detergents, etc.

Surfactants are also called

• surface active agents
• Amphiphiles
 Definition

• Surfactants are agents that reduces the surface tension b/w

two phases.
• What is a surface tension???
• Interfacial tension is the force that holds the surface of a
particular phase together and is normally measured in
dynes/cm.
• Interfacial or surface tension exists when two phases are
present. These phases can be gas/oil, oil/water, or gas/water.
 Surface tension
The molecules at the surface of liquid do not have other
molecules on all sides of them and therefore are pulled inwards.
This creates some internal pressure and forces liquid surfaces to
contract to the minimal area.
"The property of the surface of a liquid that allows it to
resist an external force, due to the cohesive nature of its
molecules.
 Structure of surfactants
Surfactants consist of two parts:
• Lipophilic (also called hydrophobic)
• Hydrophilic (also called lipophobic)

• philia means loving

• phobia means fearing
 Structure of surfactants
• Lipophilic group consisting of a long carbon chain which has
little affinity for aqueous (polar) solvents.

• Hydrophilic group consisting of polar groups such as COOH,

OH, etc. which have high affinity for polar solvents.
 Structure of surfactants
• Since surfactants have both polar and non-polar groups contributing
to affinity for both aqueous and non-polar solvents, therefore these
are called as amphiphiles.

• The amphiphiles may be hydrophilic if it is predominantly polar in

nature and lipophilic if it is predominantly non-polar in nature.

• Most surfactants have a proper balance between their hydrophilic

and lipophilic properties so that they can stay at the interface.
 How surfactants work
• When a surface active agent is added to water, it gets
preferentially adsorbed at the surface with the polar end
oriented towards water and the non-polar hydrocarbon chain
projecting upward into space.
• This surface adsorption results in the marked changes in the
surface properties of water.
 Classification of surfactants
Depending upon ionization in aqueous solutions, surfactants can
be classified as:
i. Anionic surfactants
ii. Cationic surfactants
iii. Non-ionic surfactant/zwitterionic (ampholytic)
Classification of surfactants
 Anionic surfactants

• Anionic surfactants are organic substances. When these surfactants are

dissolved in water, negatively charged particles, i.e. anions, are created
(anionic part of surfactant molecule is active while cationic part is inactive).
• It is a mixture of sodium alkyl sulfates, the chief of which is sodium dodecyl
sulfate, C12 H25 SO4 – Na+
• Very soluble in water at room temperature, and is used pharmaceutically as a
preoperative skin cleaner, having bacteriostatic action against gram-positive
bacteria, and also in medicated shampoos
• Component of emulsifying wax
 Types of Anionic surfactants
i) Alkali Soaps

• These are ammonium, potassium and sodium salts of long

chain fatty acid such as oleic acid, stearic acid, etc.

• Unstable at pH below 10.

• Examples: Potassium stearate, sodium stearate.

 Types of Anionic surfactants
ii) Amine soaps
Amine soaps are generally made by reaction between amines such as
ethanolamine, diethanolamine, triethanolamine or isopropanolamine
and fatty acids such as oleic acid.

iii) Metallic soaps

Metallic soaps consist of the salts of the divalent and trivalent metals
such as calcium, magnesium, zinc and aluminum with long chain fatty
acids. E.g. calcium stearate, aluminum stearate etc.
 Types of Anionic surfactants
iv) Alkyl sulphates and phosphates
These are the esters formed by reaction of fatty alcohols with
sulphuric acid and phosphoric acid respectively. Examples include
sodium lauryl sulphate, sodium cetostcaryl sulphate and
triethanolamine lauryl sulphate.

v) Alkyl sulphonates
These include disodium dioctyl sulfosuccinate and are effective
wetting agents.
 Cationic surfactants
• Cationic surfactants, in aqueous solutions, are ionized and after dissociation have an
active positively charged functional group (while negative part of surfactant
molecule is negative) which provides the emulsifying properties.

• Quaternary ammonium compound such as cetrimide, benzalkonium chloride and

benzethonium chloride are some examples.

• Unstable at high pH.

Applications
• As antiseptic/disinfectant agents
• Secondary emulsifying agent for external use
 Cationic surfactants
• The quaternary ammonium and pyridinium cationic surfactants
are important pharmaceutically because of their bactericidal
activity against a wide range of gram-positive and some gram-
negative organisms.
• They may be used on the skin, especially in the cleaning of
wounds.
• Their aqueous solutions are used for cleaning contaminated
utensils
 Ampholytic surfactants
These are substances whose ionic characteristics depends on the pH of
the system.
Below a certain pH, these are cationic while above a defines Ph these
are anionic.

At Intermediate pH, they behave as zwitterions.

Examples
Lecithin and N-deodecyl alanine.
 Non-ionic surfactants
• These are pharmaceutically useful surfactants.
• These comprise of largest group of surfactants.
• Compatible with both anionic and cationic surfactants.
• Unlike other surfactants, these are resistant to pH changes and effect
of electrolytes.
• Lower irritancy to intestinal mucosa.

Disadvantage
These surfactants have tendency to inactivate preservatives.
 Non-ionic surfactants
EXAMPLES
Glycerol and glycerol esters
• Glycerol monostearate
• Propylene glycol monostearate

Macrogel esters
• Polyoxyl stearate
• Polyoxyl castor oil derivatives
 Non-ionic surfactants
EXAMPLES
Macrogel ethers
Cetomacrogel 1000

Sorbitan fatty acid esters

• Span
• Tweens (polysorbates)
 Nonionic surfactants
• Unlike anionic and cationic surfactants, nonionic surfactants are
useful for oral and parenteral formulations because of their low
irritation and toxicity.
• Based on their neutral nature, they are much less sensitive to
changes in the pH of the medium and the presence of
electrolytes.
• These are available in various hydrophile–lipophile balances
(HLBs), which stabilize oil-inwater (O/W) or water-in-oil (W/O)
emulsions
 Nonionic surfactants
• Sorbitan esters (Spans)
1. Products of the esterification of a sorbitan with a fatty acid
2. Low HLB number, insoluble in water and used as W/O
emulsifiers
• Polysorbates (Tweens)
1. Ethoxylated derivatives of sorbitan esters
2. High HLB number, soluble in water and used as O/W
emulsifier
 Polymeric surfactants
• Used in many formulated products as dispersants, emulsifiers,
foam boosters, viscosity modifiers,
 Polymeric surfactants
• The most commonly used polymeric surfactants used in
pharmacy are the A–B–A block copolymers,
• A being the hydrophilic chain [poly(ethylene oxide), PEO]
• B being the hydrophobic chain [poly(propylene oxide), PPO].
• The general structure is PEO–PPO– PEO and is commercially
available with different proportions of PEO and PPO
 Pharmaceutical Uses
• Surfactants have several uses in pharmaceuticals,
• i) for solubilisation of hydrophobic drugs in aqueous media,
• ii) as components of emulsions ,
• iii) surfactant self-assembly vehicles for oral and transdermal
drug delivery,
• iv) as plasticizers in semisolid delivery systems,
• v) as agents to improve drug absorption and penetration.
 Surfactants
• With the increase in the concentration of the surfactant in an
aqueous solution, the interfacial tension is appreciably
lowered.
• Further addition leads to saturation at the surface, where the
surfactant molecules are closely packed.
• Beyond saturation, the excess surfactant moves into the bulk
and forms micelles within the aqueous solution, thereby
concluding the change in surface tension
 Surfactants
• The concentration at which micelle formation occurs is termed
critical micelle concentration (CMC).
• In the micelle, the surfactant hydrophobic groups are directed
towards the interior of the aggregate and the polar head
groups are directed towards the solvent; thus, micelles help in
solubilization of the dispersed phase.
Arrangement and orientation of surfactant molecules at surface
(at low concentration) and in bulk solution (at high
concentration).
 Application of Surfactants
Medicinal applications
• As antimicrobials:
• Cationic surfactants such as cetrimide and benzalkonium chloride have useful
antibacterial properties.
• They are used as disinfectants for instruments and as an antiseptic for the skin.
• These surfactants adsorb over the surface of the bacterial cell (Gram negative
bacteria) owing to their positive charge. This changes the cell membrane
permeability, resulting in loss of essential substances from the cell, in turn
resulting in its death.
• the mucus and results in its easy removal, thereby providing relief.
 As antimicrobial

Addition of
surfacant
 Medicinal applications
• As expectorants: In acute and chronic infections of the upper
respiratory tract (e.g. bronchitis, asthma and TB), the viscosity
of bronchial mucus increases.
• The mucus dries out, which causes difficulty in breathing.
Inhalation of sprays or mists (aerosols) containing surfactants,
such as calfactants, loosens
 Application of Surfactants
• As cleansing agents: Since surfactants have detergent
properties, these are also used as cleansing agents. However,
their repeated use should be avoided since this may cause
irritation of the skin.
• Examples of surfactants used as cleansing agents include
ammonium lauryl sulphate.
 Pharmaceutical applications
• As solubilizing agents:
Surfactants have been extensively used as solubilizing agent for a number of poorly soluble
drugs such as oil-soluble vitamins, volatile oils, hormones, phenobarbitone and
sulphonamides.
• Oil-soluble vitamins such as Vitamin A are unpleasant to take in the form of fish liver oil but
are easily palatable when administered in the form of oil in water emulsions or as solubilized
system in water.
• Such solubilized systems are more resistant to oxidation than either oily solutions or
emulsions.
• Surfactants have also been used to solubilize many disinfectant compounds such as cresol
and chloroxylenol. Lysol, which is a solution of phenol and alkali soap in water, is a very good
disinfectant.
• The disinfectant property of the compound is increased by the use of surfactants since they
also alter the permeability of the cell membrane of microorganisms..
 Pharmaceutical applications
• As wetting agents:
Their hydrophobic nature makes them aggregate and agglomerate
when added to water. Dispersions containing such hydrophobic
powders are often difficult to prepare since the powders form large
floccules or float on the surface, thereby hindering the preparation of a
uniform suspension. This can be solved by the use of surfactants, which
get adsorbed at the solid/liquid interface and increase the affinity of the
hydrophobic powder for water while reducing the attractive forces
between particles of the solid. Aerosol OT DIETHYLHEXYL SODIUM
SULFOSUCCINATE is a very good example of wetting agent
 Pharmaceutical applications
• As flocculating agents:
Use of surfactants coupled with precipitation results in the desirable action of controlled
flocculation in suspensions. For example, sulphamerazine, a hydrophobic powder, can be
dispersed by means of aerosol OT in association with aluminium ions. Although these
flocculated particles settle on standing, they do not form a hard cake and easily disperse in the
vehicle on shaking.
• As additives in semisolid preparations:
Surfactants are often added to creams and ointments to alter the release characteristics of the
incorporated drug. The release rate may be accelerated because of the absorption of water
from the surrounding environment. Further, the capacity of different ointment bases to take up
aqueous liquids can also be improved by the addition of surfactants. Various other properties
associated with surfactants are shown in Figure 4.3 and these phenomena are subsequently
explained in this chapter