3. Learning outcomes
At the conclusion of this topic, the student should
be able to:
Understand properties of different types of surfactant.
Describe importance & applications of surfactants in
pharmacy
Describe factors that influence performance of surfactants
Explain critical micellar concentration
Describe the advanced applications of surfactants in
pharmacy
4. Why does surfactant work ?
Water : Hydrophobic Hydrophilic
Oil : Lipophilic Lipophobic
5. What does surfactant do ?
Water & Oil
are mortal
enemies
Surfactants
acts as clamp
binding Water
& Oil are
together
Surface
Tension –
Force
between
two liquids
7. Surfactant
Definition
Surface Active Agent
Substance which reduces surface/interfacial tension
between two phases
Compounds having tendency to gather around
the interface between two different materials by
altering the properties of interface remarkably
Serves as good mediator to settle dispute between
two phases which are not friends
11. Nonionic
They are the class of surfactants widely used as
emulsifying agents. They are extensively used to
produce both oil in water and water in oil
emulsions for internal as well as external use.
They are not susceptible to pH change and
presence of electrolytes.
They also show low irritancy as compared to other
surfactants.
Most commonly used nonionics are
Sorbitan fatty acid esters (spans) e.g. sorbitan mono
oleate. They are oil soluble nonionic surfactants and give
w/o emulsions.
Polyoxyethylene derivatives of sorbitan fatty acid esters
(Tweens or polysorbates).They are hydrophilic and give
o/w emulsion.
13. Nonionic surfactants
Polyoxyethylene / polyoxypropylene
block polymers (Poloxamers)
Polyoxyethylene/polyoxypropylene block
polymers , also known as poloxamers
consist of combined chains of oxyethylene
with oxypropylene where the oxyethylene
portions imparts hydrophilicity and
oxypropylene portion imparts lipophilicity.
The molecules are synthesized as long
segments of hydrophilic portions combined
with long segments of the hydrophobic
portions, with each portion referred to as
block.
They are used in the formulation of i/v
emulsions and can impart structures to
vehicles and interfacial films.
15. Anionic
Primarily used for external preparations and not for internal use as they
have an unpleasant bitter taste and irritant action on the intestinal mucosa.
e.g., alkali soaps, polyvalent soaps (metallic soaps), organic soaps, sulphated
alcohols and alkyl sulphonates.
Soaps
Monovalent soaps : E.g. potassium, sodium, ammonium salts of lauric and oleic
acid . They are soluble in water. Good o/w emulsifying agents.
Polyvalent soaps : The calcium, magnesium and aluminum salts of fatty acids
(metallic soaps) are water insoluble and give w/o emulsion.
Organic soaps : Triethanol amine soaps of fatty acids give o/w emulsion.
Sulfonates : In these compounds the sulfur atom is connected
directly to the carbon atom, giving the general formula CH3(CH2)n
CH2SO3– Na+
e.g. sodium lauryl sulphate , dioctyl sulphosuccinate.
16. Cationic
The positive charge cations produced on dissociation are
responsible for emulsifying properties.
They are mainly used in external preparations such as
lotions and creams.
Quaternary ammonium compounds such as cetrimide,
benzalkonium chloride and benzethonium chloride are
examples of important cationic surfactants.
Good antibacterial activity.
Auxiliary emulsifying agents such as cetostearyl alcohol.
They are incompatible with anionic surfactants.
16
17. Ampholytic surfactants
These are the substances whose ionic charge
depends on the pH of the system. Below a
certain pH, these are cationic while above a
defined pH, these are anionic. At
intermediate pH these behave as zwitterions.
e.g. lecithin.
(carboxymethyl)dimethyloleylammonium hydroxide
Lecithin
18. Classification based on use in
industry
According to their pharmaceutical use, surfactants
can be divided into the following groups:
Emulsifying agents
Wetting agents
Solubilizing agents
Dispersing, Suspending and Deflocculating agents
Foaming and antifoaming agents
Detergents
19. Wetting effect
Paraffin or new cotton cloth barely wetted by water
But
When surfactant is added to water their surface
easily becomes wet
Surfactant in floor cleaner as a wetting agent
21. Detergents
Detergents are surfactants used for removal of dirt.
Detergency involves:
Initial wetting of the dirt and the surface to be cleaned.
Deflocculation and suspension, emulsification or
solubilisation of the dirt particles
Finally washing away the dirt.
21
22. Foaming and Anti Foaming agents
Foams are dispersion of a gas in a liquid (liquid
foams as that formed by soaps and detergents ) or
in a solid (solid foams as sponges ).
Foaming agents
Many Surfactants solutions promote the
formation of foams and stabilize them, in
pharmacy they are useful in toothpastes
compositions.
Anti Foaming agents
They break foams and reduce frothing that
may cause problems as in foaming of
solubilized liquid preparations. in pharmacy
they are useful in aerobic fermentations, steam
boilers.
22
23. Surface activity is influenced by
surfactant structure
Increase in hydrocarbon
chain of the surfactant
results in increased surface
activity
Conversely, an increase in
the hydrophilicity by
increasing the length of the
ethylene oxide chain,
results in a decreased
surface activity.
25. Insoluble monolayers
Surfactants with very
long hydrocarbon chains,
will form films on water
surfaces when it is
dissolved in a volatile
solvent and carefully
injected onto the
surface.
26. Polymer for enteric coating
Polymer monolayers are used
as models to assess the
suitability of new polymers
and of polymer mixtures as
potential enteric and film
coatings for solid dosage
forms.
The effects of substrate pH
on the properties of cellulose
acetate phthalate was
studied.
The phthalate ester formed a
much more condensed
monolayer at pH 3 than at pH
6.5 indicating its suitability
for coating
27. Surfactants and CMC
As more surfactant is added to the aqueous
medium, surface tension decreases until it
reaches it can be decreased no more.
At this point the excess surfactant
molecules will fall from the surface of the
liquid into the bulk of the liquid. This point
is called the critical micellar concentration
(CMC)
At CMC surfactants falling into the bulk of
the liquid will orient in such a way that the
hydrophobic tails will form the core of
these aggregates and are protected from
contact with water by their hydrophilic
groups, which form a shell around them.
The concentration of surfactant molecules
in the surface layer remains approximately
constant in the presence of micelles and
hence the γ–log concentration plot
becomes almost horizontal.
28. Critical Micelle Concentration
The critical micelle concentration (CMC) is defined as
the concentration of surfactants above which micelles form
and all additional surfactants added to the system go
to micelles. The CMC is an important characteristic of a
surfactant.
Most micelles are spherical and contain: between 60 and 100
surfactant molecules
29. Micelles as drug carriers
At critical micelle
concentration (CMC),
surfactants can act as
reservoir that will allow a
compound that is normally
insoluble (in the solvent being
used) to dissolve.
This occurs because the
insoluble species can be
incorporated into the micelle
core, which is itself
solubulised in the bulk solvent
by virtue of the head groups'
favorable interactions with
solvent species.
30. Micellar structure of ionic micelles
Stern layer
For most ionic micelles, the degree of ionisation (α) is between 0.2 ~
0.3; 70~80 % of the counterions may be bound to the micelles
Gouy-Chapman electrical double layer
Outer surface of the Stern layer
Contain 20~30 % counterions to neutralise the charge on the micelle
Stern layer
Gouy-Chapman layer
* Fast track – Physical Pharmacy
Alexander T Florence and David Attwood
30
31. In highly concentrated solution
The micelles elongating to form cylindrical structures with many
ionic systems.
* Physiochemical Principles of Pharmacy 4th edition
Alexander T Florence and David Attwood
31
Micellar structure of ionic micelles
32. Factors affecting the CMC and size
• Structure of the hydrophobic group
• Nature of the hydrophilic group
• Type of counterion
• Addition of electrolytes
• Temperature
32
33. Structure of the hydrophobic group
Compounds with rigid aromatic or heteroaromatic ring
structures
Purines, pyrimidines, etc.
Face-to-face stacking of molecules one on top of the other
Do not exhibit cmc
Length of Hydrocarbon chain
Increase length Increased hydrophobicity Decreased cmc
33
34. Nature of the hydrophilic group
Nonionic surfactants
Not involve any electrical work
Much lower CMC and higher aggregation number
Increase in the ethylene oxide chain length
Make more hydrophilic and the CMC increases
34
35. Type of counterion
Cationic surfactant
Cl- < Br- < I-
Anionic surfactant
Na+ < K+ < Cs+
The weakly hydrated ions can be adsorbed more readily in the
micellar surface
Decrease the charge repulsion between the polar groups
Reduction of repulsion forces by electrolytes
Lower CMC and higher micellar size
Increase in micellar size
35
36. Temperature
Cloud point
Temperature over which aqueous
solutions of nonionic surfactants
become turbid
Reversible process of phase
separation
Comparatively small effect on
ionic surfactants
36
Ionic surfactant
Nonionic surfactant
* Physiochemical Principles of Pharmacy 4th edition
Alexander T Florence and David Attwood
37. Application in surfactants
pharmaceutical field
Emulsions are stabilized by the presence of an interfacial film
between the oil and water phases.
Knowledge of the area occupied by surfactant at the interface is
important in achieving optimum stability of the emulsion.
Monolayers of surfactants can be used as in vitro models for
biologic membranes. Hence, these model systems are used to
study drug absorption across biologic membranes.
Excipient in suppository bases, suspensions, aerosols
For contact lens cleaning
38. Applications of surfactants
Exogenous surfactants in
respiratory distress therapy
Surfactant preparations are used as
replacement therapy for the
treatment of premature infants
suffering from neonatal respiratory
distress syndrome (substantial
deficiency in the endogenous lung
surfactant).
The lung surfactant preparations are
used in combination with
supplemental oxygen and
mechanical ventilation to facilitate
gas exchange for either prophylactic
or rescue treatment of neonatal
respiratory distress syndrome.
The exogenous surfactants are
either derived from animals or
synthesized
38
SURVANTA is natural bovine lung
extract. It contains 25 mg/mL
phospholipids (including 11.0-
15.5 mg/mL disaturated
phosphatidylcholine), 0.5- 1.75
mg/mL triglycerides, 1.4-3.5
mg/mL free fatty acids, and less
than 1.0 mg/mL protein.
It is suspended in 0.9% sodium
chloride solution, and heat-
sterilized. No preservatives
39. Applications of micelles
The transport of
molecules through the
skin can be increased by
the use of certain adjuvant
known as enhancers.
Ionic surfactants enhance
transdermal absorption by
disordering the lipid layer
of the stratum corneum
and by denaturation of
keratin.
Enhancers may increase
drug penetration by
causing the stratum
corneum to swell and/or
leach out some of the
structural components,
thus reducing the diffusion
resistance and increasing
the permeability of the skin
39
