Transcript Intermolecular Forces

Instructor: Rong Cui, phd, 231 Pharmacy Bldg., 7-3255
Topics to be covered:
Interfacial phenomena
Surfactants
Micelles
Emulsions
Introductions to polymers, rheology, and colloids
Ointments
Topical drug delivery
Transdermal drug delivery.
Books referred:
Pharmaceutical Dosage forms and drug delivery systems, Ansel’s et al.
Pharmaceutics: the science of dosage form design, ME Aulton
Comprehensive pharmacy review, 5th ed., by Shargel et al.
Physical pharmacy and pharmaceutical sciences, 5th ed. Sinko et al.
The theory and practice of industrial pharmacy, 3rd ed., Lachman et al.
Handbook of pharmaceutical excipients, 2nd ed., Wade and Weller
Applied therapeutics, 8th ed., Koda-Kimble et al.
Polymer process engineering, EA Gruke
Remington: the science and practice of pharmacy, 21st ed.
Goodman and Gilman’s Pharmacology, 9th ed.
Journal of Pharmaceutical Sciences
Transdermal drug delivery, 2nd ed., Guy and Hadgraft
Interfacial phenomena and surfactants
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Molecule interaction
Surface and interfacial tensions
Surfactants
Micelles
HLB systems
Other applications of surfactants
Intermolecular Forces
Ionic interactions
Hydrogen bonds
Dipole-dipole interactions
London dispersion forces
(van der Waals forces)
1,000
100
10
1
Hydrogen bond
Hydrogen bonding occurs when a hydrogen atom is covalently bound
to a small highly electronegative atom such as nitrogen, oxygen, or
fluorine. The result is a dipolar molecule. The hydrogen atom has a
partial positive charge δ+ and can interact with another highly
electronegative atom in an adjacent molecule (again N, O, or F). This
results in a stabilizing interaction that binds the two molecules
together. An important example is water.
Dipole-dipole interactions
• Dipole-dipole interactions are the forces
that occur between two molecules with
permanent dipoles (spatially oriented δ+
within a molecule). These work in a similar
manner to ionic interactions, but are
weaker because only partial charges are
involved. An example of this can be seen
in hydrochloric acid:
Van der Waals force
• Also called London forces or
instantaneous dipole effects (spatially
variable δ+) these involve the attraction
between temporarily induced dipoles in
nonpolar molecules (often disappear
within a second).
Interfacial Phenomena
Water strider, from
Wikipedia
Surface tension is an effect within the surface layer of a liquid that
causes the layer to behave as an elastic sheet.
Surface and interfacial tension
• Surface tension =
tendency of liquids to
reduce their exposed
surface to the smallest
possible area.
Work = g ΔA
Work required to increase the
surface area A of a liquid by 1
area unit.
mN/m = dynes/cm
Interfacial tension
• At interfacial region/boundary/interface between
two immiscible liquids or liquid-solid.
Interfacial tension
Surface active agents
• Any substance that when
dissolved in water or an aqueous
solution reduces its surface
tension or the interfacial tension
between it and another liquid.
Also called surfactant
• Surfactants are usually organic
compounds that are
amphipathic, meaning they
contain both hydrophobic groups
(their "tails") and hydrophilic
groups (their "heads").
Therefore, they are typically
sparingly soluble in both organic
solvents and water.
Requirements for surfactants
Classification of surfactants
• Anionic
• Cationic
• Zwitterionic
(amphoteric)
• Non-ionic
Anionic surfactants
Laureth sulfate
Soaps = salts of fatty acids
• Soft soap: positive ion is univalent, such
as Na+, K+, and NH4+.
• Hard soap: positive ion is divalent, such as
Ca++, Mg++
Cationic surfactants
CTAB
Non-ionic surfactants
SPAN®
SPAN
Tween & poloxmers
Structure of Tweens
How do surfactants decrease surface tension?
Surfactants decrease surface tension
Effect of surfactants on the properties of a liquid
• Osmotic pressure
increases and reaches
constant
• Detergency ability
increases sharply
• Light scattering
becomes significant
• Surface tension
decreases and reaches
a constant (critical
micelle concentration)
Micelle
A micelle is an aggregate of the
surfactant molecules dispersed in a liquid
colloid. Colloid = a kind of dispersed
system with particle size ranging from 1
nm to 0.5 mm. Aggregation number
Cholesterol-bearing pullulan selfaggregates (micelles)
Micelle
• Critical micelle concentration
The concentration of surfactant at which micelles form.
• Micelle aggregation number
The number of surfactants that aggregate to form a micelle.
• CMC of the mixture of two surfactants
1/CMC = f1/CMC1 + f1/CMC2
(f = mole fraction)
Micelles are not a solid particles. The individual molecules in the
micelles are in dynamic equilibrium with monomers in the bulk
and at the interface.
CMC and aggregation # of some surfactants
Factors affecting CMC and micelle size
• Structure of hydrophobic
group
• Nature of hydrophilic
group
• Nature of counter ions
• Addition of electrolytes to
ionic surfactants
decreases CMC and
increase size
• Effect of temperature
Solubilization
• The ability of the micelles to increase the solubility of
materials that are normally insoluble or only slight soluble
in the dispersion medium.
Systems of hydrophile-lipophile classification
• Hydrophilic-lipophilic
balance
The higher the HLB, the
more hydrophilic.
• Required HLB (RHLB)
values for emulsion.
HLB system
HLB of blending of surfactants
• HLB values are additive
If 20 mL of an HLB of 9.0 are required, what will be the ratio of two
surfactants (with HLB values of 8 and 12) in the blend?
HLB value of surfactant A = 8
HLB value of surfactant B = 12
Let the weight fraction of A = x; the weight fraction of B will be (1-X).
8X + 12 (1-X) = 9; 8X + 12 -12X = 9; -4X = -3
X = 3/4; 1-X = 1- ¾ = ¼
The ratio of A to B, A/B = 3:1
alligation
B=
12
1
B=
15.6
9
A= 8
7.3
12
3
A = 4.7
4
3.6
10.9
B=¼
B = Tween 40 = 7.3/10.9
A = 3/4
A = Span 60 = 3.6/10.9
An example of HLB calculation
• HLB of Tween 80 = 15
• HLB of Span 80 = 4.3
• We need 2 g of Tween 80 and Span 80 blend having a
HLB value of 10.6. How much Tween 80 and Span 80
are needed?
• Suppose we need X fraction of Tween 80; the fraction of
Span 80 will be 1-X
• 15X + 4.3 (1-X) = 10.6; X = (10.6-4.3)/(15-4.3) = 0.59
• Fraction of Span 80 = 1- 0.59 = 0.41
• Weight of Tween 80 = 2 * 0.59 = 1.18 g
• Weight of Span 80 = 2 * 0.41 = 0.82 g
HLB calculation
B=
15
6.3
10.6
A = 4.3
4.4
10.7
B = Tween 80 = 6.3/10.7
A = Span 80 = 4.4/10.7
Applications of surfactants
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Detergents
Emulsifiers
Paints
Adhesives
Inks
Alveoli
Wetting
Ski Wax
Snowboard Wax
Foaming
Defoaming
Laxatives
Agrochemical formulations
Herbicides
Insecticides
Wetting agent
• A wetting agent is a
surfactant that, when
dissolved in water, lowers the
advancing contact angle,
aids in displacing an air
phase at the surface, and
replacing it with a liquid
phase.
• Wetting agents can lower the
contact angle.
• Wetting agents should have
an HLB value of 6-9.
gc = 26-28
dynes/cm for
real human
skin
Liquid
Water
Glycerin
Diiodomethane
Ethylene
glycol
Benzyl
alcohol
Mineral
oil
g (dynes/cm)
72.8
63.4
50.8
48.3
39.2
31.9
Cosθ
0.45
0.56
0.79
0.77
0.96
0.97
Detergent
• Surfactants used for the
removal of dirt.
• Initial wetting of the dirt and
of the surface to be cleaned;
• Deflocculation and
suspension;
• Emulsification or
solubilization of dirt;
• Foaming of the agent for
entrainment and washing
away.
Foaming and anti-foaming agents
• Any solutions containing
surfactants 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 is
being stabilized by a foaming
agent.
• Agents that can disrupt/break
foams are anti-foaming agents.