Liquid crystals

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Transcript Liquid crystals

Part 1
Liquid Crystals
Surfactant + water >>>> different phases.
Phase type determined by:
• Surfactant concentration (illustrating figures)
• Temperature (GMO binary phase diagrams)
• Additives (ternary phase diagrams)
Liquid crystals are substaces that exhibit a phase of
matter that has properties between those of a
conventional liquid, and those of a solid crystal.
Hence LC show anisotropy.
Liquid crystals are either lyotropic or thermotropic.
The ‘‘ideal’’ sequence of phases as a function of amphiphile concentration.
Names and abbreviations for the different mesophases are:
micelles (L1),
micellar cubic (I1),
hexagonal (H1),
bicontinuous cubic (v1),
lamellar (La),
reversed bicontinuous cubic (v2),
reversed hexagonal (H2),
reversed micellar cubic (I2),
and reversed micelles (L2),
where subscripts 1 and 2 refer to ‘‘normal’’ and ‘‘reversed’’ phases, respectively.
Lamellar phases can be found in different phase states, including: lamellar crystalline
(Lc), lamellar gel (Lb), and lamellar fluid (La).
Ref. Phys. Chem. Chem. Phys., 2006, 8, 4957–4975 | 4957
Figure: In a system of water, ionic surfactant, and long-chain alcohol three
phases are important cosmetically.
The aqueou solution (lower left) contains spherical micelies, the lameliar liquid
crystal is located in the middle, and the alcohol solution (top) contains inverse
J. Soc. Cosmet. Chem., 41, 155-171 (May/June 1990)
Pictures of different systems
made by a polarized
Micellar and reverse micellar
have no optical activity.
Ref. Langmuir, Vol. 20, No. 5,
2004 1643
Part 2
Liquid Crystal in Cosmetics
Lipids in the SC are organized in a bilayer LC-like
Skin dryness is prevented by keeping liquid like nature
of the bilayers.
Moisturising agents are required to improve skin
hydration and increase water retention.
Lamellar LCs are good candidate.
What are the components of the LC base?
a Fatty surfactant: GMO, long chain alcohols,..
(too lipophilic to stabilize o/w emulsion alone)
b high HLB surfactant.
What is the phases produced when dispersing a or b in water
separately and combined ?
a too hydrophobic to form swollen lamellar phase
b forms only micelles
a and b >gel structure (b penetrates the layers of a and permits
swelling and lamellar liquid crystal formation)
Heating followed by cooling >> lamellar crystalline gel network
Figure: In a system of water, ionic surfactant, and long-chain alcohol three
phases are important cosmetically.
The aqueou solution (lower left) contains spherical micelies, the lameliar liquid
crystal is located in the middle, and the alcohol solution (top) contains inverse
J. Soc. Cosmet. Chem., 41, 155-171 (May/June 1990)
How does the lamellar LC phases form?
At optimum blend of a and b.
structure for
the lamellar
LC (at T>Tk)
Suggested structure for
the lamellar gel phase
(at T<Tk)
Advantages of the LC phases:
• emulsion definition: “An emulsion is a mixture
of two liquids, one of which is dispersed in the
other in the form of liquid droplets and/or as
liquid crystals”
• emulsion stability,
• Prolong hydration properties,
• Controlled drug delivery,
• Easy to formulate,
• Well-liked skin feel.
Part 3
Formulation of an oral dosage form utilizing the
properties of cubic liquid
crystalline phases of glyceryl monooleate
Ref.: European Journal of Pharmaceutics and Biopharmaceutics 53 (2002) 343–
GMO: FDA -approved food additive,
The unique properties of cubic liquid crystalline phases
formed from GMO systems have been utilized for the
preparation of controlled release systems and in topical
and mucosal drug delivery systems due to their
adhesive properties.
Investigated model drug: Furosemide (diuretic).
Disadvantage of conventional dosage forms: low
bioavailability and short period of peak diuresis.
Suggested solutions:
Sustained release formulations (showed reduced
bioavailability of the drug in comparison with
immediate release dosage forms),
Modified release dosage form having a longer gastric
residence time (a correlation was made between
gastrointestinal transit and furosemide).
Investigation of the cubic liquid crystalline
phases of GMO to formulate an oral drug
delivery system for furosemide.
Furosemide when dispersed in GMO and filled
into hard gelatin capsules is expected, when
exposed to gastrointestinal fluids at body
temperature, to swell forming the cubic liquid
crystalline phase. The system is expected:
To produce sustained release,
To be retained in the stomach through
its bioadhesive nature.
Glyceryl Monooleate
Also known as monoolein or GMO
Polar lipid, insoluble but swallable in water,
Semisolid, melting point 35-37 deg.
1. Preparation of different GMO mixtures
a. Preparation of GMO-drug mixtures:
GMO > melt (at 45deg in water bath)> add furosemide, PEG 400 and trisodium
phosphate (TSP)> continuous mixing > complete dispersion.
Store at 5 C in a dark place.
b. Samples for phase diagram construction:
GMO in glass vials>melt> add warm aqueous media (water, or simulated
intestinal fluids without enzymes (SIF)
or simulated gastric fluids without enzymes (SGF)) >mix.
c. Samples for additives effect on the cubic phase formation:
GMO in glass vials>melt> add additives > add warm distilled sufficient to form
the cubic phase.
Store the well closed samples (b, c) at 37 C in a dark place for 12 h in order to
reach equilibrium conditions before testing.
Identification of GMO phases
Observation of viscosities and optical properties changes upon heating at constant
rate (4 C/ min) on a hot stage connected to polarizing microscope.
Reversed micellar phase (L2): clear liquid and isotropic.
Cubic phase: very viscous gel and isotropic
Other phases were less viscous than the cubic liquid crystalline phase and
look radiant when viewed between crossed polarizers.
Lamellar phase (La) had a pattern of ‘oily streaks’ and Maltese crosses;
Reversed hexagonal phase: fan-like textures.
The results proved that the cubic phase of GMO would exist at body
temperature in the presence of gastrointestinal fluid.
Fig. 1. Phase diagrams of (a) GMO/distilled
water system, (b) GMO/SIF system, (c)
GMO/SGF system. SIF, simulated intestinal
fluid; SGF, simulated gastric fluid; L2, reversed
micellar phase; La, lamellar phase; C, cubic
phase; HII, reversed hexagonal phase.
Fig. 2. Phase diagram of GMO containing 5% furosemide in water.
Observation of the melting behavior of GMO:
furosemide and their mixtures using a hot-stage
microscope at 4 C/min heating rate.
Thermal analysis:
DSC thermograms of GMO, furosemide each alone and
in mixtures were recorded at heating rate of 10
For mixtures containing furosemide and GMO, the
endothermic event attributed to the melting o GMO
was not affected by the presence of furosemide.
Partitioning of furosemide between aqueous test
solutions and GMO in the cubic liquid crystalline
• known concentration of furosemide + test solution
placed in a 100-ml stoppered conical flask in a shaker
water bath maintained at 37.0 deg., protected from
light to avoid photodegradation of Furosemide,
• Add One gram of GMO to each flask with continuous
• At selected time interval, withdraw 5-ml aliquots,
were filter, through a 0.45-mm membrane filter and
measure furosemide concentration
• Runs were done in triplicate.
The apparent lipid bilayer/water partition coefficient of furosemide
versus the corresponding pH value (at 37 C).
Dissolution tests:
Samples accurately weighed containing the
equivalent of 40 mg furosemide were filled
into hard gelatin transparent capsule size (0)
and used for dissolution testing within 24 h of
Dissolution tests were carried out in triplicates
using USP apparatus II (paddle) (protected
from light).
Release rates of furosemide from GMO containing different drug
loadings in comparison with an immediate release furosemide capsule
using SGF at 37 C
Effect of changing the pH of the dissolution medium on the release
rate of furosemide from formula containing furosemide/TSP/PEG 400/
GMO (5:5:10:80) using apparatus I; 100 rpm.
……… A formula containing furosemide/TSP/PEG
400/GMO in the ratio 5:5:10:80, respectively, was
found to have optimum properties concerning
release characteristics and mucoadhesion.
However, future work needs to b concentrated on the
evaluation of in vivo mucoadhesive studies on the
selected formulation.
Polarized Microscope
Q.1 What does it mean for the light to be
“Polarized” ?
Natural sunlight and almost every other form of
artificial illumination transmits light waves
whose electric field vectors vibrate in all
perpendicular planes with respect to the
direction of propagation.
A light wave that is vibrating in more than one
plane is referred to as unpolarized light.
If the electric field vectors are restricted to a
single plane by filtration of the beam with
specialized materials, then the light is referred
to as plane or linearly polarized with respect
to the direction of propagation, and all waves
vibrating in a single plane are termed plane
parallel or plane-polarized.
Q.2 What is meant by Plane and crossed polarized light?
In the figure, the incident light electric field vectors are vibrating perpendicular to the
direction of propagation in an equal distribution of all planes before encountering
the first polarizer.
Polarizer 1 is oriented vertically to the incident beam so it will pass only the waves that
are vertical in the incident beam. The wave passing through polarizer 1 is
subsequently blocked by polarizer 2 because the second polarizer is oriented
horizontally with respect to the electric field vector in the light wave.
The concept of using two polarizers oriented at right angles with respect to each other is
commonly termed crossed polarization and is fundamental to the practice of
polarized light microscopy.
Image contrast arises
from the interaction of
plane-polarized light
with a birefringent
specimen to produce
two individual wave
components that are
each polarized in
perpendicular planes.
The velocities of these
components are
different and vary
with the propagation
direction through the
When an anisotropic
specimen is brought
into focus and rotated
through 360 degrees
on a circular polarized
light microscope stage,
it will sequentially
appear bright and
Optical Activity
Many molecules have an interesting property in that they can rotate polarized light.
Some drugs molecules can rotate or change the direction the light vibrates, so if we place
a container of the drug solution in the light path, between the two filters (polarizers)
in the figure , then in order to look “light,” or “dark”, the second filter will have to be
rotated differently to make up for how much the drug molecule rotates the light.
Drugs can be identified by which direction and how much it rotates the light.
For example, glucose rotates polarized light to the right so it’s also known as dextrose.
Fructose rotates polarized light to the left, so it’s also known as levulose.
Origins of optical activity.
An electronic transition is the result of the movement of charges when a
molecule is exposed to light. The electronic transition has an
associated magnetic transition that is perpendicular to it.
The energy of a transition depends on the electric dipole moment and
the magnetic dipole moment induced by the action of light on the
electrons in the molecule. The rotational strength of a transition is the
imaginary part of the dot product of the electric dipole induced by the
light and the magnetic dipole induced by the light.
If a molecule has a plane or center of symmetry either the sum of all the
induced electric and magnetic dipoles is zero, or the vectors
representing the magnetic and electric dipoles are perpendicular to
one another. The result is that there is no optical activity since the
cosine of 90 deg. equals 0.
There are several cases showing asymmetry in the molecule and in these
cases the molecule is optically active.
The End