Introduction to surfactants Flashcards
Surfactants
Surfactants are amphiphiles, i.e., they have two distinct regions in their chemical
structure:
1. Hydrophilic – Water-loving
2. Hydrophobic – Water-fearing
Surfactants are used as
solubilizing, emulsifying and wetting agents
Surfactants are Generally classified according to the
nature of their hydrophilic group (anionic,
cationic, zwitterionic and nonionic
Hydrophobic portions are usually
saturated or unsaturated hydrocarbon chains or,
less commonly, heterocyclic or aromatic ring systems
Anionic surfactants
The most widely used class of surfactant
- The most commonly encountered anionic surfactants have carboxylate, sulfate, sulfonate and phosphate polar groups in combination with counterions such as
sodium and potassium (for water solubility) or calcium and magnesium (for oil
solubility)
Anionic surfactants example
Sodium lauryl sulfate – Used as a wetting and emulsifying agent
Cationic surfactants
the charge is carried on a nitrogen atom as,
for example, with amine and quaternary ammonium surfactants
• The quaternary ammonium compounds retain this charge over the whole pH range,
whereas amine-based compounds only function as surfactants in the protonated
state and therefore cannot be used at high pH
Cationic surfactants example
Benzalkonium chloride – An important preservative in the preparation of
ophthalmic and nasal solutions
Zwitterionic (or amphoteric)
surfactants
possess polar head groups which on ionization can impart both positive and negative charges
- Show excellent compatibility with other classes of surfactant
Zwitterionic (or amphoteric)
surfactants charges?
The positive charge is almost always carried by an ammonium group and the
negative charge is often a carboxylate
Zwitterionic (or amphoteric)
surfactants example
Cocamidopropyl betaine (CAPB) – Used in skin cleansers because of its thickening and foaming properties
Nonionic surfactants
By far the most common nonionic surfactants are those with a poly(oxyethylene)
chain as the hydrophilic group
• The longer the poly(oxyethylene) chain, the higher the aqueous solubility
Nonionic surfactants example
Polyoxyethylene sorbitan esters of fatty acids – Used to solubilize steroids
in ophthalmic formulations
Hydrophilic-lipophilic balance (HLB)
system
Originally conceived for nonionic surfactants
• Each surfactant is assigned a number, which represents the percentage weight of the
hydrophilic group divided by 5, in order to limit the range from 0 to 20
• Higher the number, the more hydrophilic is the surfactant
For a 100% hydrophilic molecule, as in polyethylene glycol, the HLB value is
20
Surfactant as a solubilizing agent
A high HLB value (15-18) is needed for use as a solubilizing agent
Surfactant as an emulsifying agent
HLB values from 8 to 18 produce oil-in-water (O/W) emulsions
– HLB values of 3 to 6 produce water-in-oil (W/O) emulsions
– The emulsifier must be more soluble in the continuous phase than in the dispersed phase
Surfactant as a wetting agent
An HLB range of 7-9 has been recommended for wetting agents
Surface tension –
Force per unit length that must be applied parallel to the surface as to counterbalance the net inward pull
Interfacial tension
Force per unit length existing at the interface between two immiscible liquid phases
Surface and interfacial tensions,
continued
Amphiphilic molecules orient themselves at the surface or interface in such a way as
to remove the hydrophobic group from the aqueous environment
• Intrusion of surfactant molecules results in water molecules being replaced by the
hydrophobic groups of the surfactants
• Forces of intermolecular attraction between the water and hydrophobic groups is less
than those that exist between water molecules
Surface activity increases with
an increase in overall hydrophobicity
Surface activity decreases with an
increase in overall hydrophilicity
Lowering of surface tension increases with
increase of surfactant until the critical micelle concentration (CMC) is reached
Critical micelle concentration
CMC
Surface layer is saturated with surfactant molecules and no further decrease in surface tension possible
• At this concentration, surfactant forms micelles
Micelles
An alternative means of shielding the hydrophobic portion of the amphiphiles from the aqueous environment
• Hydrophobic groups of the surfactants form the core and are protected from contact with water by their hydrophilic groups
Primary reason for micelle formation
is the attainment of a state of minimum
free energy
association colloids
There is continuous movement of molecules between the surface and the solution below
– Micelles are continuously breaking down and reforming
At low concentration
amphiphiles can achieve an adequate decrease in the overall free energy of the system by accumulation at the surface or interface in such a way as to remove the hydrophobic group from the aqueous environment
As concentration increases
this method of energy reduction becomes inadequate
and the monomers form into micelles
Free energy change is due
to changes in enthalpy and entropy
➢ ∆G = ∆H - T∆S
For micellar systems
the entropy term is by far the most important in determining the
free energy changes
Loss of the ordered structure of the water molecules when the hydrophobic regions of the
surfactant are removed results
in an increase in entropy
Factors that affect CMC and micellar size
Shape of the micelle formed
- an increase in hydrophobic chain length decreases CMC and increases
micellar size
- nonionic surfactants have lower CMC values and form larger micelles than
their ionic counterparts
- Addition of electrolytes to ionic surfactants decreases the CMC and increases
micellar size by reducing repulsion between charged head groups and therefore
decreasing electrical work of micellization
Solubility review
Rule: “Likes dissolve likes”
– The extent to which one substance dissolves in another depends on the nature of both the
solute and solvent
– Solubility depends on chemical, electrical and structural effects that lead to mutual
interactions between the solute and the solvent
The stronger the interactions between solute and solvent
the greater the solubility
Solubilization
Process whereby water-insoluble substances are brought into solution by incorporation into micelles
Maximum additive concentration
Maximum amount of solubilizate (incorporated
substance) that can be incorporated at a fixed concentration of surfactant
Extent of solubilization is influenced
by the volume of the core, lipophilicity of the
solubilizate, temperature and, for nonionic micelles, the ethylene oxide chain length of surfactants
Phospholipids and other surfactants having two hydrophobic chains tend to
form lamellar phases
Liposomes
Formed by phospholipids
– When first formed, are composed of several bimolecular lipid lamellae separated by aqueous
layers (multilamellar)
– Sonication of these units can give rise unilamellar vesicles
– Water soluble drugs can be entrapped in the aqueous layers
– Lipid-soluble drugs can be solubilized within the hydrocarbon interiors of the bilayers
(membrane
Adsorption of surfactants at the oil/water interface
lowers interfacial tension between
phases, facilitating emulsion formation
Continuous phase =
Internal phase =
= water
= oiL
Emulsions
Allows the pharmacist to prepare a relatively stable homogenous mixture of
two immiscible liquids
• Permits palatable administration of a distasteful oil
• Medicinal agents that irritate the skin are less irritating in the internal phase
• Can be used for drug deliverY
Adsorption at the solid-liquid
interface
• Two types
- Physical – Adsorbate is bound to the surface through weak van der Waals forces
- Chemical – Involves stronger valence forces
Greater the solubility of a solute in a particular solvent,
the lower the extent of
adsorption on to the solid
The more finely divided or porous the solid
the greater its adsorption capacity
Excessive amounts of wetting agents may lead t
To foaming or impart an undesirable taste or odor to the formulation
Water has a high surface tension, so is
NOT a good wetting agent
Good
wetting agents include
alcohol, glycerin, and propylene glycol. Also
surfactants such as benzalkonium chloride and sodium lauryl sulfate
-
Insoluble monolayers
Dissolve surfactant with a long hydrocarbon chain, which is insufficiently watersoluble, in a suitable volatile solvent and carefully inject the solution on to the surface
of an aqueous solvent
• There is no equilibrium with the bulk solution because of the low water solubility of the
surfactant
• Useful to assess the properties of polymers for use as packaging materials and film
coatings for solid dosage forms
