Faculty of Pharmacy &
Drug Manufacturing
PHYSICAL PHARMACY
Surface Active Agents (SAA)
“Surfactants”
Surfactants or surface active agents S.A.A
➢ Are solutes or molecules that are adsorbed at the surface of a liquid
or at the interface between two liquids, reducing the surface or
interfacial tension.
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Surfactants or surface active agents S.A.A
➢ Composition of soluble surfactants:
A. lipophilic or hydrophobic group consisting of a
long chain carbon which has little affinity for
aqueous (polar) solvents
B. hydrophilic or lipophobic group consisting of
polar group such as –COOH or –OH…etc.
which has affinity for polar solvents.
➢ These surfactants have both polar and non polar
groups contributing to affinity for both
aqueous and non aqueous (polar and non
polar solvents), these are termed "amphiphils" .
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Surfactants and surface tension
Hydrophilic Lipophilic Balance (HLB) - system
➢ Surfactants contain both polar and non polar groups in their molecules.
Surfactants with more polar groups hydrophilic, mostly.
Surfactants with more non-polar groups lipophilic, mostly.
➢ The balance between the hydrophilic and lipophilic nature of surfactants
is given by HLB-system which consists of arbitrary scale of values to
different surfactants based on their HLB.
𝑴𝒉 Mh: molecular weight of hydrophilic group.
𝑯𝑳𝑩 = 𝟐𝟎 × Mt molecular weight of the whole molecules.
𝑴𝒕
➢ In the HLB-system, each surfactant has a number typically between 1-20
representing the relative proportions of lipophilic and hydrophilic parts
of molecule.
The higher the number more hydrophilic.
The lower the number more lipophilic. 3
𝟏𝟎𝟒𝟒
HLB = 20 x = 17
𝟏𝟐𝟐𝟔
Calculate the HLB value of Merj 49 (polyoxyethylene)21stearate knowing that total
m.w = 1024?
Oxyethylene m.w = 44 Da
Hydrophilic groups (Mh) = 44 x 21 = 924
Total M.W (Mt) = 1024 (given)
𝑀ℎ 924
𝐻𝐿𝐵 = 20 × = 20 × = 18
𝑀𝑡 1024
Depending on HLB value for each surfactant different uses will be
shown.
HLB-values Surfactants
1 Oleic acid
3.8 Glyceryl monostearate (pure)
4.3 Sorbitan monooleate (Span 80)
4.7 Sorbitan monostearate (Span 60)
6.7 Sorbitan monopalmitate (Span 40)
8 Glyceryl monostearate (Self emulsifying)
8.6 Gum acacia
12 Sorbitan monolaurate (Span 20)
15 Triethanolamine oleate
16 Polyoxyethylene sorbitan monooleate (Tween 80)
17 Polyoxyethylene sorbitan monolaurate (Tween 20)
40 Sodium lauryl sulphate
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Classification of surfactants
(1)Anionic (2)Cationic (3)Nonionic (4)Amphoteric
(1) Anionic Surfactants:
• which on dissociation release long chain anion giving the surface activity with
general formula of sulfate (OSO3-) while the cationic part is inactive.
• These surfactants are not suitable for oral use because they have unpleasant taste
and irritant action to the mucosa.
Examples:-
a. Alkali soaps: they are unstable below pH 10, are incompatible with acids e.g. potassium
and sodium stearate.
b. Amine soaps: as triethanolamine oleate produced from reactions of amines
(triethanolamine) with fatty acids as oleic acid.
c. Metallic soaps: salts of divalent or trivalent metals with long chain fatty acids as oleic
acid.
d. Alkyl sulfates and phosphates: are esters formed by reaction of fatty
alcohols with sulfuric or phosphoric acid e.g. sodium lauryl sulfate.
e. Alkyl sulfonate: including Dioctyl sodium sulfo succinate.
(2) Cationic surfactants:
• They must be ionized or dissociated to be effective.
• In aqueous solutions dissociate to form +ve cations which give the surface
activity ( emulsifying properties) with general formula of trimethyl ammonium
N(CH3)3+.
• They are used as antiseptic, emulsifiers and preservative.
Example:
quaternary ammonium compounds such as cetrimide (Cetyl trimethyl ammonium
bromide ) and benzalkonium chloride (Benzyl trimethyl ammonium chloride) .
(3)Ampholytic (Amphoteric) surfactants:
They are substances whose ionic characters depend on the pH of
the system.
Below a certain pH (acidic) cation,
above the defined pH (alkaline) anionic
while at intermediated pH zwitterions.
Example: lecithin, N-dodecyl-alanine.
.
(4) Non-ionic surfactants:
The largest group used in the pharmaceutical preparations.
Advantages
a- compatible with anionic and cationic S.A.A. b-resist the PH changes.
c- resist the effect of electrolytes. d-less irritant.
Disadvantages:
Tend to inactivate preservation of phenolic or carboxylic groups.
Example:
1. Brij & merj 2
2. Spans
3. Tweens
4. Macrogol esters or polyethylene glycol (PEG)
5. Glycerol monostearate
MICELLE FORMATION
• An important property of surfactants is the capacity to aggregate in solution.
• The aggregation process depends on the surfactants and condition of the system in
which they are dissolved.
• The abrupt change in physicochemical properties seen when a specific
concentration is exceeded which result in the formation of oriented colloidal
aggregates.
How micelles are formed?
1. On addition of surfactants to water → the surfactant molecules
(monomers) orient themselves at the liquid-air interface.
2. On adding more surfactants → the monomers adsorbed at the surface will
be crowded till occupy the interface → the molecule of surfactant is
compressed at the surface → crowded monomers.
3. On further addition of surfactant → the molecules of surfactant aggregate into
micelles.
Monomers Spherical micelle cylindrical micelle Lamillar micelle
WHY MICELLES ARE FORMED?
1. To achieve a state of minimum free energy (more stability).
2. To remove hydrophobic group form aqueous solution.
CRITICAL MICELLE CONCENTRATION (CMC)
• The concentration at which micelles are formed.
• It is the concentration of the surfactant above which it will migrate
to the bulk and start to form micelles and show the minimum
value of surface tension.
Factors affecting CMC
1) Molecular structure of the surface active agent
(A) The hydrocarbon chain the hydrophobic part:
• Chain length: the increase in chain length → ↑ micelle size so ↓ CMC.
• Branched hydrocarbon chain: branching → ↑ in CMC.
Since the chain must come together in the micelle
• Unsaturation: the CMC is increased 3 - 4 times by the presence of double
bond compared with saturated compounds.
(B) The hydrophilic group:
• Type of hydrophilic group: if the ionic dissociation is complete
→ small effect on CMC.
• Number of hydrophilic groups: increase in number → ↑ in solubility
of surfactant → ↑ in CMC.
• Position of hydrophilic group: when polar groups move from the terminal
position to the middle → ↑ in CMC.
2) Effect of additives
(A) Simple electrolytes: addition of salts → ↓ in CMC.
(B) Alcohols: ↓ in CMC → aids the micelle formation.
(C) Hydrocarbons: ↓ in CMC and micelle formation is facilitated.
(D) Other surfactants: ↓ or ↑ in CMC.
3) Effect of temperature:
• Non-ionic surfactants → The value of CMC first decreases with increase in
temperature to certain minimum and then increases with further increase in
temperature..
• As the temperature increases, hydrogen bonding between the hydrophilic groups and the
water molecules is weakened and dehydration of the hydrophilic groups occurs. Thus, the
surfactant molecule becomes more hydrophobic due to decreased hydration of the
hydrophilic group which favors micellization (lower CMC)
• Also, temperature increases also produces distortion in the structure of water
surrounding the hydrophobic group, an effect that disfavors micellization (higher
CMC)
• The relative magnitude of the tow opposing effects, therefore, determines whether
the CMC increases or decreases over a particular temperature range,
• Ionic surfactants → temperature has a small effect on the micelle property.
Applications of surface active agents
(1) Medical applications:
A- As antimicrobials: quaternary ammonium compounds such as benzalkonium
chloride has useful antibacterial properties and used as disinfectant for
instruments and as antimicrobial agents in eye drops and creams.
B- As expectorants: by decreasing the viscosity of bronchial mucous on
inhalation of sprays containing surfactants in cases of acute and chronic
infections of upper respiratory tract.
C- As cleansing agents: surfactants have detergent properties.
(2) Pharmaceutical applications:
A- As solubilizing agents:
• S A A s are used extensively as solubilizing agents for Also, poorly
soluble drugs such as oil soluble vitamins, volatile oils, hormones…etc.
• Also, as solubilizers for many disinfectants compounds as cresol or
chloroxylenol and the disinfectant property is increased by the use of SAA by
altering (changing) the permeability of the cell membrane of
microorganism.
B- As wetting agents:
• surfactants adsorbed at the solid /liquid interface between the powder
particles and the solvent leading to increase in affinity of hydrophobic
powder of water.
C- As flocculating agents:
• surfactants make controlled flocculation for powder particles in suspensions
preventing cake formation.
D- As emulsifying agents:
• acting by reducing the interfacial tension between the oil phase and water
phase by forming the stable interfacial film between them e.g. tween and span.
E- As additives in semisolid preparations:
• are added to ointments and creams to change the release characteristic of
the incorporated drug resulting increase in absorption through the skin.
