DISPERSE SYSTEM
In which one substance is distributed in
particulate form throughout another
Two types
Emulsion
Is
a biphasic liquid preparation containing two immiscible liquids one of which is
dispersed as minute globules into other and stabilized by a third substance
called emulsifying agent.
The
droplet phase is called the dispersed phase or internal phase and the liquid in
which droplets are dispersed is called the external (continuous phase).
Suspension
Is
a two phased system in which a finely divided solid is dispersed in a
continuous phase of solid, liquid, or gas.
The
droplet phase is called the dispersed phase or internal phase and the liquid in
which droplets are dispersed is called the external (continuous phase).
Classification of Emulsion
Based on:
|
Oil
in Water (O/W): Oil droplets
dispersed in water
Water
in Oil (W/O): Water droplets
dispersed in oil
(Diameter greater than
0.1 μm)
|
|
Simple
emulsions
(Macro
emulsions)
|
|
Multiple
emulsions
|
|
Oil-in-water-in-oil
(O/W/O)
Water-in-oil-in-water
(W/O/W)
|
|
Nano emulsions
Thermodynamically stable optically transparent, mixtures of a
biphasic oil –water system stabilized with surfactants
0.01 – 0.2 mm Micro emulsions (Thermody-namically stable)
|
|
Micro
emulsions
|
TYPES OFEMULSIONS:
1.
Macroemulsions (Simple Emulsions):
I. Oil in water (o/w): Oil droplets are dispersed
in a continuous aqueous phase. This emulsion is generally formed if the aqueous
phase constitutes more than 45 % of the total weight and a hydrophilic
emulsifier is used. These are [referred for oral administration and cosmetics. These
are useful as water washable drug bases .The globule size is 0.25 to 10
microns.
ii. Water in oil (w/o): Aqueous droplets are dispersed in continuous
oily phase. . This emulsion is generally formed if the oily phase constitutes
more than 45 % of the total weight and a lipophobic emulsifier is used. These
are used for cosmetics. They are employed for treatment of dry skin and
emollient applications.
2. Multiple emulsions:
Types of multiple emulsions: w/o/w , o/w/o
They
are developed with a view to delay the release of an active ingredient. They
have three phases. They may be oil-in-water-in-oil
(o/w/o) or of water-in-oil-in-water (w/o/w). An emulsifier is present to
stabilize the emulsions and various ionic and nonionic surfactants are
available for this purpose. Lipophilic (oil-soluble, low HLB) surfactants are
used to stabilize w/o emulsions, whereas hydrophilic (water-soluble, high HLB)
surfactants are used to stabilize o/w systems In these emulsions within
emulsions any drug present in innermost phase must now cross two phase boundaries to reach the
external continuous phase. Such emulsions also can invert. However, during
inversion they form simple emulsions. So a w/o/w emulsion will get inverted to
o/w emulsion.
Preparation of multiple emulsions:
Aqueous
phase is added to oily phase, containing a lipophilic surfactant. Upon mixing a
w/o emulsion is formed. This w/o emulsion is then poured into a second aqueous solution,contain
za hydrophilic surfactant. Upon mixing multiple emulsion w/o/w is formed.
3.
Microemulsions:
They may be defined as dispersions of
insoluble liquids in a second liquid that appears clear and homogenous to the
naked eye. They are frequently called solubilised systems because on a
macroscopic basis they seem to behave as true solutions. Terms as transparent emulsions, micellar
solutions, solubilised systems, and swollen micelle have all been applied to
the same or similar systems.
These emulsions appear to be
transparent to the eye. They have globule radius below the range of 10-75 nm.
The appearance of emulsion depends on the wavelength of visible light i.e.
globules less than 120 nm do not reflect light and appear transparent to the
eye. As in microemulsions the globule size is less than 120 nm, they appear to
be transparent.
USES (APPLICATIONS) OF EMULSIONS:
Emulsions
can be used for oral, parenteral or topical pharmaceutical dosage forms.
i.
Oral Products
Emulsions
are used for administering drugs orally due to following reasons:
a.
More palatable: Objectionable taste or texture of medicinal agents gets masked.
b.
Better absorption: Due to small globule size, the medicinal agent gets absorbed
faster.
ii. Topical products:
O/W emulsions are more acceptable as water washable
drug bases for cosmetic purposes.
W/O emulsions are used for treatment of dry skin.
Emulsions have following advanyages when used for topical purpose:
A.
Patient acceptance: Emulsions
are accepted by patients due to their elegance, easily
B.
washable character,
C.
acceptable viscosity,
D.
less greasiness.
iii.
Parenteral Emulsions:
A.
i.v rout: Lipid nutrients are emulsified and given to
patients by i/v rout. Such emulsions have particle size less than 100 nm.
B.
Depot injections : W/o
emulsions are used to disperse water soluble antigenic materials in mineral oil
for i/m depot injection.
iii.
Diagnostic purposes:
iv.
Radio opaque emulsions have
been used in X-ray examination.
Identification test of emulsion
Dilution test:
In this test the emulsion is
diluted either with oil or water. If the emulsion is o/w type and it is diluted
with water, it will remain stable as water is the dispersion medium" but
if it is diluted with oil, the emulsion will break as oil and water are not miscible with each
other.
o/w emulsion can be diluted
with water.
w/o emulsion can be diluted with oil.
Conductivity Test
The basic principle of this
test is that water is a good conductor of electricity. Therefore in case of o/w
emulsion, this test will be positive as water is the external phase. ‘In this
test, an assembly is used in which a pair of electrodes
connected to an electric bulb is dipped into an emulsion. If the emulsion is
o/w type, the electric bulb glows.’
Dye-Solubility Test
In this test an emulsion is mixed with a water soluble dye (amaranth)
and observed under the microscope. If the continuous phase appears red, it
means that the emulsion is o/w type as water is in the external phase and the
dye will dissolve in it to give color. If the scattered globules appear red and
continuous phase colorless, then it is w/o type. Similarly if an oil soluble
dye (Scarlet red C or Sudan III) is added to an emulsion and the continuous
phase appears red, then it is w/o emulsion.
Fluorescence Test:
Oils give fluorescence under UV light, while water
doesn’t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion
fluoresces. When a w/o emulsion is
exposed to fluorescent light under a microscope the entire field fluorescence.
If the fluorescence is spotty, then the emulsion is of o/w-type. However, all
oils do not exhibit fluorescence under UV light and thus the method does not
have universal application. It is necessary that the results obtained by one
method should always be confirmed by means of other methods
Cobalt Chloride Test:
Filter paper impregnated with CoCl2 and dried appear
to be blue but when dipped in o/w emulsion changes to pink. This test may fail
if emulsion unstable or breaks in presence of electrolyte.
FORMULATION OF EMULSIONS
1. Emulsifying agents (emulsifiers)
2. Antioxidants (Stabilizers)
3. Antimicrobial preservatives
4. Colours and flavourings
Emulsifying agents (emulsifiers):
An
emulsifying agent is any material that enhances the stability of an emulsion
(i.e. Prevention of coalescence and reducing creaming).The ideal emulsifying
agent is colourless, odourless, tasteless, non-toxic, non-irritant and able to
produce stable emulsions at low concentrations.
Classification of Hydrocolloid emulsifying
agents
i.
Hydrocolloids.
ii.
Surface active agents (SAA)
(surfactants).
iii.
Finely divided solids.
iv.
Auxiliary emulsifiers.
Natural
emulsifying agents. :
Natural
(Multimolecular films)
Ø From
plant origin Polysaccharides ( Acacia, tragacanth, agar, pectin, lecithin) o/w
emulsions.
Ø From
animal origin
Ø Proteins
( Gelatin) o/w emulsions.
Ø Lecithin,
o/w i/v emulsion
Ø Cholesterol.
w/o
Ø Wool fat,
w/o
i. Natural emulsifying agents from vegetable sources
These consist of agents which are carbohydrates and
include gums and mucilaginous substances. Since these substances are of
variable chemical composition, these exhibit considerable variation in
emulsifying properties. They are anionic in nature and produce o/w emulsions.
They act as primary emulsifying agents as well as secondary emulsifying agents
(emulsion stabilizers). Since carbohydrates acts a good medium for the growth
of microorganism, therefore emulsions prepared using these emulsifying agents
have to be suitable preserved in order to prevent microbial contamination. E.g.
tragacanth, acacia, agar, chondrus (Irish moss), pectin and starch.
Acacia:It is a carbohydrate gum which is soluble over a wide
pH range. Tragacanth, pectin and starch are used as auxiliary emulsifying
agents.
ii. Natural emulsifying agents from animal source
The examples include gelatin, egg yolk and wool fat
(anhydrous lanolin).
Gelatin:
It is a protein .It has two isoelectric points,
depending on the method of preparation. Type a gelatin derived from acid
treated precursor, has an isoelectric point between pH 7 and 9. Type B gelatin
obtained from an alkaline precursor has an isoelectric point around pH 5. .
Type A gelatin acts best as an emulsifier around pH 3 where it is -vely chaged:
On the other hand type B gelatin suitable as emulsifier at pH 8 where it is
–vely charged.Type A gelatin (Cationic) is generally used for preparing o/w
emulsion while type B gelatin is used for o/w emulsions of pH 8 and above.
Lecithin:
It is an emulsifier obtained from both plant
(soyabean) and animal (e.g. egg yolk) sources and is composed of phosphatides.
Although the primary component of most
lecithins is phosphatidyl choline. But it also contains phosphatidyl srine,
phosphatidyl inositol, phosphatdylethanloamine and phosphatidic acid.. It
imparts a net –ve charge to dispersed particles. They show surface activity and
are used for formulating o/w emulsions. Lecithins are good emulsifying agents
for naturally occurring oils such as soy, corn, or safflower. Purified lecithin
from soy or egg yolk is used for i/v emulsions.
cholesterol:
It is a major constituent of wool alcohols, obtained
by the saponification and fractionation of wool fat. It forms w/o emulsion. It
is because of cholesterol that wool fat absorbs water and form a w/o emulsion
It is also present in egg yolk.
Wool fat
It is mainly used in w/o emulsions meant for external
use. They absorb large quantities of water and form stable w/o emulsions with
other oils and fats.
Classification of Surfactant emulsifying agents
Ø Synthetic (Surfactants)
( Monomolecular films)
·
Cationic
·
Quaternary ammonium compounds
Ø Nonionic
·
Glyceryl esters
·
Sorbitan fatty acid esters
·
Polyoxyethylene polyoxypopylene esters (Macrogels)
·
Polyoxyethylene derivatives of sorbitan fatty acid
esters (polysorbate)
Synthetic emulsifying agents (Surfactants):
This group contains surface active agents which act by
getting adsorbed at the oil water interface in such a way that the hydrophilic
polar groups are oriented towards water and lipophillic non polar groups are
oriented towards oil, thus forming a stable film. This film acts as a
mechanical barrier and prevents coalescence of the globules of the dispersed
phase. They are classified according to the ionic charge possessed by the
molecules of the surfactant e.g., anionic, cationic, non-ionic and
ampholytic.They may be subdivided into anionic, cationic and nonionic
surfactants.
i. Anionic Surfactants:The long
anion chain on dissociation imparts surface activity, while the cation is
inactive. These agents are 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.
a. Monovalent soaps: E.g.
potassium, sodium, ammonium salts of lauric and oleic acid. They are soluble in
water and are good o/w emulsifying agents.
Disadvantages:
They have disagreeable taste and are irritating to the
GIT.. So they are useful only for external use emulsions.
They have a high pH . They get ppted below pH 10 because
the unionized fatty acid is formed which has a low aqueous solubility. So
emulsions formed with alkali soaps are not stable at pH less than 10.
b. Polyvalent soaps: The
calcium, magnesium and aluminum salts of fatty acids (metallic soaps) are water
insoluble and give w/o emulsion.
c. Organic soaps:
Triethanol amine soaps of fatty acids give o/w emulsion. They are used for
external use emulsions. They are less alkaline as compare to monovalent soaps. They
can act till pH 8.00
d. Sulfated alcohols: They
are neutralized estrs of sulfuric acid and fatty alcohols. They can be used as
auxiliary emulsifying agents. E.g Sodium lauryl sulphate
e. 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.
ii. Cationic Surfactants: 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. These compounds besides having good antibacterial
activity are also used in combination with secondary emulsifying agents to
produce o/w emulsions for external application.
Quaternary ammonium
compounds (cetyl trimethyl ammonium bromide; cetrimide)
CH3 (CH2)14 N+ (CH3)34Br
They have marked bactericidal activity. So they are
useful for anti-infective products such as skin lotions and creams. The pH of
an emulsion prepared with cationic emulsifier is in pH 4 -6 range. This is the
range of normal pH of skin. So they are suitable for skin. They are
comparatively weak emulsifying agents, so they are used along with auxiliary
emulsifying agents such as cetostearyl alcohol. They are incompatible with
anionic surfactants.
Nonionics :
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.
Advantages: 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
- glyceryl
esters ,
- polyoxyethylene
glycol esters and ethers
- sorbitan fatty acid esters (spans)
- polyoxyethylene
derivatives of sorbitan fatty acid esters (Tweens or polysorbates)
- Polyoxyethylene
/ polyoxypropylene block polymers (Poloxamers)
- Glyceryl esters : e.g. glyceryl mono stearate. It is too
lipophilic to be used as a primary emulsifying agent. It is used as
auxiliary emulsifying agent.
Sorbitan fatty acid esters : e.g.
sorbitan mono oleate. They are oil soluble nonionic surfactants.and give w/o
emulsions.
- Polyoxyethylene derivatives of sorbitans
fatty acids : They are hydrophilic and give o/w emulsion.
- Polyoxyethylene/polyoxypropylene block poymers ,
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 hydrophilic 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.
- 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 cationic. At intermediate pH these behave as
zwitterions. e.g. lecithin.
- Includes
mainly cellulose derivatives like sodium carboxy methyl cellulose, hydroxyl
propyl cellulose and methyl cellulose. They are used for formulating o/w
type of emulsions. They primarily act by increasing the viscosity of the
system. e.g., methyl cellulose, hydroxypropyl cellulose and sodium carboxy
methyl cellulose
Finely dispersed solids:
Finely divided solid particles that are wetted to some
degree by both oil and water act as emulsifying agents. This results from their
being concentrated at interface, where they produce a particulate film around
the dispersed droplets to prevent coalescence.They form particulate films
around the dispersed droplets, producing emulsions which are coarse grained but
stable. Colloidal clays like bentonite, veegum are the examples of finely
divided solids used as emulsifying agents.
Bentonite : It is a gray, odorless and tasteless powder which
swells in the presence of water to form a suspension with a pH of about 9.
Depend on the order of mixing, both o/w or w/o emulsion can be formed with
bentonite. For o/w emulsion, bentonite is first dispersed in water and allowed
to hydrate to form magma. Then oil phase is gradually added with constant
agitation. To prepare w/o emulsion, bentonite is first dispersed in oil and
then water is added gradually.
Veegum : Used as
stabilizer in concentration of 1% for
cosmetic lotions and creams.
Prepared with anionic or non-ionic emulsifying agents.
Auxiliary
emulsifying agents
Auxiliary (Secondary) emulsifying agents include those
compounds that are normally incapable themselves of forming stable emulsion.
Their main value lies in their ability to function as thickening agents and thereby
help stabilize the emulsion.These are those compounds which normally cannot
form an emulsion on their own but can function as thickening agents and
stabilize the emulsion. Sometimes they increase the viscosity of the external
phase and help restricting the collisions of droplets.. Some of them prevent
coalescence by reducing van de waals forces between particles or by providing a
physical barrier between droplets. Proteins, semisynthetic polysaccharides (methyl
cellulose, carboxy mthyl cellulose), clays can be used as auxiliary agents.
Antimicrobial agents
Emulsions often contain a number of ingredients such
as carbohydrates, proteins, sterols and phosphatides.All of which readily
support the growth of a varity of microorganisms. Even in the absence of any of
the above mentioned ingredients, the mere presence of a mixture of lipid and
water in intimate contact frequently allows microorganisms growth. So
preservative is a must for emulsions. Microbial
contamination may occur due to:Contamination during development or
production of emulsion or during its use.Usage of impure raw materials.Poor
sanitation conditions.
Invasion by an opportunistic microorganisms.Contamination by the consumer
during use of the product. Precautions
to prevent microbial growth ;Use of uncontaminated raw materialsCareful
cleaning of equipment with live straem .
Preservation :
Once a microbiologically uncontaminated product has
been formed, a relatively mild antimicrobial agent is sufficient to protect the
product against microbial contamination. The preservative system must be
effective against invasion by a variety of pathogenic organisms and protect the
product during use by consumer.The preservative must be :Less toxic, Stable to
heat and storage, Chemically compatible, Reasonable cost, Acceptable taste,
odor and color.Effective against fungus, yeast, bacteria.
Available in oil and aqueous phase at effective level
concentration.
•
Acids and acid derivatives - Benzoic acid - Antifungal
agent
•
Aldehydes
– Formaldehyde - Broad spectrum
•
Phenolics - Phenol - Broad spectrum
Cresol
Propyl p-hydroxy benzoate
•
Quaternaries -Chlorhexidine and salts - Broad spectrum
Benzalkonium chloride
Cetyl trimethyl ammonium bromide
•
Mercurials -Phenyl mercuric acetate - Broad spectrum
Colours and flavourings
Colour is rarely needed in an emulsion, as most have
an elegant white colour and thick texture. Emulsions for oral use will usually
contain some flavouring agent.
The HLB ( Hydrophilic lipophilic balance system):
An HLB number (1-20) represents the relative
proportions of the lipophilic and hydrophilic parts of the molecule. High
numbers (8-18) indicate a hydrophilic molecule, and produce an o/w emulsion.Low
numbers (3-6) indicate a lipophilic molecule and produce a w/o emulsion. Oils
and waxy materials have a 'required HLB number' which helps in the selection of
appropriate emulsifying agents when formulating emulsions. Liquid paraffin, for
example, has a required HLB value of 4 to obtain a w/o emulsion and 12 for an
o/w emulsion.
HLB ca. 3.5 to 8: Water-in-Oil Emulsifiers
HLB ca. 1 to 3.5: Antifoams
HLB ca. 7 to 9: Wetting and spreading agents
HLB ca. 8 to 16: Oil-in-Water Emulsifiers
HLB ca. 13 to 16: Detergents
HLB ca. 15 to 40: Solubilizers
Methods of Preparation Of Emulsions
Commercially, emulsions are prepared in large volume
mixing tanks and refined and stabilized by passage through a colloid mill or
homogenizer. Extemporaneous production is more concerned with small scale
methods.
1) Dry Gum Methods
2) Wet Gum Methods
3) Bottle Method
4) Beaker Method.
5) In situ Soap Method
DRY GUM Method
(Continental method)
Dry gum method is used to prepare the initial or
primary emulsion from oil, water, and a hydrocolloid or "gum" type
emulsifier. (4 parts oil, 2 parts water,
and 1 part Emulsifier).
Ratio of oil: gum: water in primary emulsion
Fixed oil =
4:1:2
Mineral oil =
3:1:2
Volatile oil =
2:1;2
Procedure: Take mortar, 1 part gum is levigated with the 4
parts oil until the powder is thoroughly wetted; then the 2 parts water are
added all at once, and the mixture is vigorously triturated until the primary
emulsion formed is creamy white and produces a "crackling" sound as
it is triturated. Active ingredients, preservatives, color, flavors are added
as a solution to the primary emulsion. When all agents have been incorporated,
the emulsion should be transferred to a calibrated vessel, brought to final
volume with water.Oil
soluble substances in small amounts may be incorporated directly into the
primary emulsion. Any substance which
might reduce the physical stability of the emulsion, such as alcohol ( which
may precipitate the gum) should be added as near to the end of the process as
possible to avoid breaking the emulsion. When all agents have been incorporated
, the emulsion should be transferred to a calibrated vessel, brought to final
volume with water, then homogenized or blended to ensure uniform distribution
of ingredients.
Wet Gum
Method (English method)
(Oil 4 parts + Water 2 parts + Emulsifier 1 parts)
Procedure: In this method, the proportions of oil, water, and
emulsifier are the same (4:2:1), but the order and techniques of mixing are
different. The 1 part gum is triturated with 2 parts water to form a mucilage;
then the 4 parts oil is added slowly, in portions, while triturating. After all
the oil is added, the mixture is triturated for several minutes to form the
primary emulsion. Then other ingredients may be added as in the continental
method. Generally speaking, the English method is more difficult to perform
successfully, especially with more viscous oils, but may result in a more
stable emulsion.
Bottle Method
This method may be used to prepare emulsions of
volatile oils, Oleaginous substances of very low viscosities.This method is a
variation of the dry gum method. One part powdered acacia (or other gum) is
placed in a dry bottle and four parts oil are added. The bottle is capped and
thoroughly shaken. To this, the required volume of water is added all at once,
and the mixture is shaken thoroughly until the primary emulsion forms.
Beaker
Method
The most appropriate method. Dividing components into
water soluble and oil soluble components. All oil soluble components are
dissolved in the oily phase in one beaker and all water soluble components are
dissolved in the water in a separate beaker. Oleaginous components are melted
and both phases are heated to approximately 70°Cover a water bath. The internal
phase is then added to the external phase with stirring until the product
reaches room temperature.
In situ
Soap Method
Two types of Soaps developed by this Methods:
1) Calcium Soaps
2) Soft Soaps
Calcium Soaps: W/O type Emulsions. E.g.
Oleic acid + Lime water. Prepared by simple mixing of equal volumes of Oil and
Lime water.Emulsifying agent used is Calcium salt of free fatty acids. E.g.
Olive Oil + Oleic acid (FAA) = calcium Oleate.Advantage: O/W is external Phase
used frequently on dry skin and sun
burned skin.
Large
Scale Methods
Physical parameters affecting the droplet size
distribution viscosity, and stability of emulsion: Location of the emulsifier,
method of incorporation of the phases, the rates of addition , the temperature
of each phase and the rate of cooling after mixing of the phases considerably
Energy may be supplied in the form of:
¢ Heat
¢ Homogenization
¢ Agitation
Mechanical equipment for
emulsification (Agitation)
Mechanical Stirrers
An emulsion may be stirred
by means of various impellers mounted on shafts, which are placed directly into
the system to be emulsified. This is used for mixing, suspending, milling,
dispersing, disintegrating solids etc. & reduces batch time. It consists of
stator and rotor assembly. The rotor rotates inside the stator assembly which
is fixed with three tie rods to the motor.
Propeller Mixers
Simple top entering
propeller mixers are adequate for routine development work in the laboratory
and production.The degree of agitation is controlled by propeller rotation but
the pattern of liquid flow and resultant efficiency of mixing are controlled by the type of impeller, its
position in the container, the presence of baffles, and the general shape of
the container. These stirrers can not be used when :vigorous agitation is needed,
Extremely small droplets
are needed.
Foaming at high shear rates
must be avoided.These mixers may have
paddle blades, counter rotating blades or planetary blades .
¢ Homogenizers
In homogenizers the
dispersion of two liquids is achieved by forcing their mixture through a small
inlet orifice at big pressures. Homogenizers can be made with more than one
emulsifying stage, and it is possible to recycle the emulsion through the
homogenizer more than one time. Homogenizers raise the temp. Of the emulsion,
hence cooling may be required. It can be used when a reasonably mono disperse
emulsion of small droplet size (1 nm) is required.
Colloid Mills
They operate on principle
of high shear which is normally generated between rotor and stator of the mill.Colloid
mill consists of a fixed stator plate and a high speed rotating rotator plea.
Material drawn or pumped
through an adjustable gap set between the rotor and stator is homogenized by
the physical action and the centrifugal force is created by high rotation of
the rotor which operates within 0.005 to0.010 inch of the stator
Ultrasonifiers
Ultrasonic energy s used to
produce pharmaceutical emulsions. These transduced piezoelectric devices have
limited output and are expensive. They are useful for laboratory preparation of
emulsions of moderate viscosity and extremely low particle size. Commercial
equipment is based n principle of Pohlmn liquid whistle. The dispersion is
forced through an orifice at modest pressure and is allowed to impinge on a
blade. The pressure range is from 150-350 psi . This pressure causes blade to
vibrate rapidly to produce an ultrasonic note. When the system reaches a steady
state, a cavitational field is generated at the leading edge of the blade and
the pressure fluctuations of approx. 60 tones psi can be achieved in commercial
equipment.
Emulsions for oral use
Quantities for primary emulsions
Quantities for primary emulsions
Example: Calculate the
quantities for a primary emulsion for the following:
Cod liver
oil 30 ml
Water to 100 ml
Answer: Primary emulsion quantities:
Cod liver
oil is a fixed oil, therefore the primary emulsion proportions are 4 : 2 : 1
.Hence:
Cod liver oil 30
ml 4
Water
15 ml 2
Powdered acacia gum 7.5g 1
If the proportion of oil is too small, modifications
must be made. Acacia emulsions containing less than 20% oil tend to cream
readily. A bland, inert oil, such as arachis, sesame, cottonseed or maize oil,
should be added to increase the amount of oil and so prevent this from
happening. Care should be taken in selection of the bulking oil because of the
increasing incidence of nut allergy. It is often, therefore, advisable to avoid
oils such as arachis, especially for children.
Example: Rx Calciferol solution, 0.15 ml per 5 ml
dose.
Answer: The percentage of oil in each dose is 3%. The
oil content must be made up to at least 20% to produce a stable emulsion. Since 20% of 5 ml = 1 ml the volume of bland
oil required is 1-0.15 = 0.85 ml
Formula for primary emulsion (for 50 mL)
Calciferol solution 1.5 ml 4
Cottonseed oil 8.5 ml
Water 5 ml 2
Acacia 2.5g 1
The primary emulsion may not form and a thin oily
liquid is formed instead. Possible causes are:
Phase inversion has occurred, incorrect quantities of
oil or water were used, and Cross-contamination of water and oil, a wet mortar
was used,
The mortar was too small and curved or the pestle was
too round giving insufficient shear, Excessive mixing of oil and gum before adding water
(dry gum method),
Diluting the primary emulsion too soon or too rapid
dilution of primary emulsion,
Poor-quality acacia
Prepare 200ml cod liver oil emulsion to the following
formula:
Cod liver oil 60 ml
Chloroform 0.4ml
Cinnamon water to 200ml
100ml Liquid Paraffin Oral
Emulsion BP 1968.
Liquid paraffin 50ml
Vanillin 50mg
Chloroform 0.25ml
Benzoic acid solution 2ml
Methylcellulose 20 2g
Saccharin sodium 5mg
Water to 100ml
Emulsions
for external use
Liquid or semi-liquid emulsions may be used as
applications, liniments and lotions. The extemporaneous preparation of
emulsions for external use does not require the preparation of a primary
emulsion. Soaps are commonly used as the emulsifying agent and some are
prepared 'in situ' by mixing the oily phase containing a fatty acid and the
aqueous phase containing the alkali. Alternatively the emulsifying agent can be
dissolved in the oily or aqueous phase and the disperse phase added to the
continuous phase, either gradually or in one portion.Creams are semisolid
emulsions which may be o/w (e.g. aqueous cream) or w/o (e.g. oily cream).
Applications: solutions or emulsions that frequently contain parasiticides.
Liniments: alcoholic or oily solutions or emulsions designed to be rubbed into
the skin. The medicament is usually a rubefacient.Lotions : aqueous solutions,
suspensions or emulsions that cool inflamed skin and deposit a protective layer
of solid.
Creams are semisolid emulsions which may be o/w (e.g.
aqueous cream) or w/o (e.g. oily cream).
Rx 100ml Oily Calamine
Lotion 1980
Calamine 5g
Wool fat 1g
Oleic acid 0.5ml
Arachis oil 50ml
Calcium hydroxide
solution to 100ml
Shelf
life, storage, containers
Emulsions should be stored at room temperature and
will either be recently or freshly prepared. Some official preparations will
have specific expiry dates. They should not be frozen.A plain amber medicine
bottle is used for internal use with an airtight child-resistant
closures.Containers with a wide mouth are useful for very viscous preparations.
Instability
of emulsions
1)
Flocculation and creaming
2)
Coalescence and breaking
3)
Phase inversion.
4) Miscellaneous
physical and chemical changes
Flocculation
Neighboring globules come
closer to each other and form colonies in the continuous phase. This
aggregation of globules is not clearly visible. This is the initial stage that
leads to instability. Flocculation of the dispersed phase may take place before,
during or after creaming.The extent of flocculation of globules depends on
(a)
globule size distribution.
(b)
charge on the globule surface.
(c)
viscosity of the external medium.
a.
Globule size distribution
Uniform
sized globules prevent flocculation. This can be achieved by proper size
reduction process.
b.
Charge on the globule surface
A
charge on the globules exert repulsive forces with the neighboring globules. This
can be achieved by using ionic emulsifying agent, electrolytes etc.
c.
Viscosity of the external medium.
If the viscosity of the external medium is
increased, the globules become relatively immobile and flocculation can be
prevented. This can be obtained by adding viscosity improving agents (bodying
agents or thickening agents) such as hydrocolloids or waxes. Flocs slowly move
either upward or downward leading to creaming. Flocculation is due to the
interaction of attractive and repulsive forces, whereas creaming is due to
density differences in the two phases.
Creaming
Creaming is the
concentration of globules at the top or bottom of the emulsion. Droplets larger
than 1 mm may settle preferentially to the top or the bottom under gravitational
forces.Creaming may also be observed on account of the difference of individual
globules (movement rather than flocs). It can be observed by a difference in
color shade of the layers.It is a
reversible process, i.e., cream can be redispersed easily by agitation, this is
possible because the oil globules are still surrounded by the protective sheath
of the emulsifier. Creaming results in a lack of uniformity of drug
distribution. This leads to variable dosage. Therefore, the emulsion should be
shaken thoroughly before use. Creaming is of two types, upward creaming and
downward creaming
Upward creaming, is due to the dispersed phase is less
dense than the continuous phase. This is normally observed in o/w emulsions. The velocity of
sedimentation becomes negative.Downward creaming occurs if the dispersed phase
is heavier than the continuous phase. Due to gravitational pull, the globules
settle down. This is normally observed in w/o emulsions.Since creaming involves the movement of globules in
an emulsion, Stokes’ law can be applied.
ν = d2 (ρs – ρ0)g
18 η0
ν = terminal velocity in
cm/sec,
d is the diameter of the particle in cm,
ρs and ρ0 are the
densities of the dispersed phase and dispersion medium respectively,
g is the acceleration due to gravity and
η0 is the
viscosity of the dispersion medium in poise.
Creaming is influenced by,
– Globule
size
– Viscosity
of the dispersion medium
– Difference
in the densities of dispersed phase and dispersion medium.
Creaming can be reduced or prevented by:
Reducing the particle size by homogenization. Doubling
the diameter of oil globules increases the creaming rate by a factor of
four.Increasing the viscosity of the external phase by adding the thickening
agents such as methyl cellulose tragacanth or sodium alginate.Reducing the difference in the densities
between the dispersed phase and dispersion medium. Adjusting the continuous
phase and dispersed phase densities to the same value should eliminate the
tendency to cream. To make densities equal, oil soluble substances such as
bromoform, β-bromonaphthalene
are added to the oil phase (rarely used technique).
Coalescence
If the sizes of globules are
not uniform, globules of smaller size occupy the spaces between the larger
globules. A few globules tend to fuse with each other and form bigger
globules.This type of closed packing induces greater cohesion which leads to
coalescence. In this process, the emulsifier film around the globules is
destroyed to a certain extent. This step can be recognized by increased globule
size and reduced number of globules.
Coalescence is observed due
to:
Ø Insufficient amount of the emulsifying agent.
Ø Altered partitioning of the emulsifying agent.
Ø Incompatibilities between emulsifying agents.
Phase volume ratio of an
emulsion has a secondary influence on the stability of the product and
represents the relative volume of water to oil in emulsion.At higher ratio
(>74% of oil to water), globules are closely packed, wherein small globules
occupy the void spaces between bigger globules.Thus globules get compressed and
become irregular in shape, which leads to fusion of adjacent globules.Ostwald
and others have shown that if one attempts to incorporate more than about 74%
of oil in an o/w emulsion, the oil globules often coalesce and the emulsion
breaks. This value known as the critical point, is defined as the concentration
of the dispersed phase above which the emulsifying agent cannot produce a
stable emulsion of the desired type.
Breaking (cracking)
Separation of the internal
phase from the external phase is called breaking of the emulsion. This is
indicated by complete separation of oil and aqueous phases, is an irreversible
process, i.e., simple mixing fails. It is to resuspend the globules into an uniform
emulsion. In breaking, the protective sheath around the globules is completely
destroyed and oil tends to coalesce.
Phase inversion
This involves the change of
emulsion type from o/w to w/o or vice versa.
When we intend to prepare
one type of emulsion say o/w, and if the final emulsion turns out to be w/o, it
can be termed as a sign of instability. It may due to
• By addition of an electrolyte
• By changing Phase-Volume ratio
• By temperature change
• By changing emulsifying agent
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