Liquid orals

Presented by: Gadekar Punam Sukhadev

Assistant Professor
Department of pharmaceutics
 Solution
⚫ Solutions are homogenous, clear liquid preparations consist of one or
more active ingredients dissolved in suitable solvent.
⚫ Solution is made up of two parts: One is solute which is dissolved
medium and other part is solvent. which is dissolving medium of
the solution.
⚫ The general solvents used in solutions are: Water, Oil, Alcohol,
Propylene Glycol.
 ADVANTAGES OF SOLUTIONS
1. Solution are easier to swallow and suitable for children and old age
people.
2. Solution have rapid onset of action when taken orally. Absorption of
drug from solution dosage form is immediate as compared to
solid dosage form.
3. Solution provide uniform dose distribution throughout the preparation
due to the homogeneous nature.
4. Solution are more acceptable due to pleasing appearance.
5. They are easy to measure if precise measuring instruments are used.
6. The drugs which have irritant action on gastric mucosa (for example:
aspirin, potassium chloride) are administered in solution
form because of immediate dilution by the gastric contents.
 Disadvantages of solution
1. The tastes of the medicament in solution are more pronounced. It is
difficult to mask unpleasant taste.
2. Bulky preparation therefore unsuitable to transport and store.
3. Chances of inaccurate measurements of dose if precise
measuring instruments is not available.
4. Poorly soluble drugs present difficulties during formulation.
5. Solutions are prone to hydrolysis. Therefore , the stability of dosage form
is a major problem.
6. Solution are more susceptible to bacterial microorganisms. As water is
commonly used vehicle, which is prone to microbial growth. So
addition of preservative is needed.
Formulation of
solution
Followings are used in the formulation of pharmaceutical
solutions.

1. drug solubility
2. Vehicle
3. Preservatives
4. Colorants
5. Flavours
6. Sweeteners
7. Buffering agent
8. Viscosity modifiers
9. antioxidants
 SUSPENSION

⚫ A Suspension is defined as a heterogenous system in which solid particles (i.e.

dispersed phase) is uniformly dispersed in liquid medium (i.e. continuous
phase).
⚫ The suspensions is called coarse suspension in which the size of particle is greater
than ~1 mm and if particle size is below 1 mm, then it is called colloidal suspension.
⚫ When the suspension containing therapeutically active particles, then it is known as
pharmaceutical suspension.
 ADVANTAGES
• Suspension can improve chemical stability of insoluble drug, example, procaine
Penicillin G
• Easy to swallow for children and old patients.
• Drug in suspension exhibit a higher BA compared to other LDF.
• Insoluble drug may be more palatable. Suspended insoluble particle powder are
easy to swallow.
• Suspension can mask the unpleasant or bitter taste of drug, example,
Chloramphenicol palmitate.

DISADVANTAGES
• Accuracy of dosage is less reliable.
• Suspension are bulky, difficult to transport and prone to container breakages.
• Preparation requires shaking before use.
• Physical stability, sedimentation and compaction can cause problems.
• Suspension are difficult toformulate.
Desirable features of good suspension:
1. The suspended molecules should not settle rapidly
2. The particles which settle down should not deposit at the bottom as hard
cake. They must be easily re-suspended by moderate shaking.
3. It should be easy to pour
4. It should be free from grittiness.
5. The suspension should have pleasant Odour, colour and palatability.
6. It should be stable in case of physical, chemical and microbial attack.
7. It should be easily flow out from syringe needle.
8. The suspended material should be stable in the medium.

Classification of suspension
9. Based On General Classes
a. Antacid suspension, Ex. Magaldrate and simethicone oral suspension
b. Antibacterial suspension, Ex. Ciprofloxacin Oral suspension
c. Analgesic suspension, Ex. Paracetamol oral suspension
d. Anticancer suspension for IV injection, Ex. Paclitaxel
e. Antidiarrheal suspension for IM injection Ex. Ampicillin suspension
f. Topical lotion for skin condition, Ex. Hydrocortisone topical suspension
2. Based on Proportion of Solid Particles
a.Dilute suspension: A suspension considered to be dilute when the
concentration ranges from 2 to 10%w/v solid. Eg: cortisone acetate, prednisolone acetate
b. Concentrated suspension: A suspension considered to be concentrated when
the concentration ranges from 50% w/v solid. Eg: zinc oxide suspension.

3. Based on Electrokinetic Nature of Solid Particles

a. Flocculated suspension: example, Cefuroxime Axetil for oral suspension
b. Deflocculated suspension: Example, Paracetamol oral suspension

4. Based on particle size:

c. Nano suspension: (10-100nm), Ex. Celecoxib suspension
d. Colloidal suspension: (1nm-0.5 mm), Ex. Acacia Suspension
e. Coarse suspension: (>0.5 mm), Ex. Calamine Lotion

5. Based on route of administration:

f. Oral Suspension: Ex, calcium tetracycline HCL suspension
g. Topical Suspension: Ex, Calamine Lotion
h. Ophthalmic suspension: Ex, ciprofloxacin Ear Drops
 3. Based on electrokinetic:
Flocculated suspension Deflocculated suspension

In Flocculated suspension, particles In Deflocculated suspension,

form loose aggregates particles remain dispersed
Rate of sedimentation is high Rate of sedimentation is low
It does not form hard cake It form hard cake
On shaking sediment can be easily On shaking sediment is difficult to
redispersed redisperse.
Flocculated suspension is not good Deflocculated suspension
in appearance is
pleasing in appearance
Less bioavailability More bioavailability
Not pleasing in appearance Pleasing in appearance
The floccules stick to the bottle walls They don’t stick to the sides of the
bottles
Supernatant liquid is generally clear Supernatant liquid is cloudy
INGREDIENTS USED IN FORMULATION OF SUSPENSION

1. Wetting agents:
• The dispersion of insoluble powder in a vehicle is major step during the formulation
of suspension.
• Powders those are not easily wetted by water such as sulfur, charcoal and
magnesium stearate are called as hydrophobic.
• For the powders that are not easily wetted, wetting agents such as surfactants,
hydrophilic polymers and solvents are used. Surfactants are used to lowers the
solid-liquid interfacial tension. They act by displacement of air from
hydrophobic material and allow the liquid to surround the particles for
proper dispersion.
• Hydrophilic polymers such as sodium carboxymethyl cellulose, certain
water- insoluble hydrophilic material such as bentonite, aluminum-magnesium
silicates, and colloidal silica, either alone or in combination are also used.
• Solvents such as alcohol, glycerol and glycols which are water miscible are also
used to decrease the liquid/ air interfacial tension.
2. Flocculating agents:
Controlled flocculation of particles is obtained by adding flocculating agents such as
electrolytes, surfactants and polymers. The flocs are advantageous because they
do not form hard cake and easily redisperse.

a.Electrolytes:
They act as flocculating agents. They lessen the electric barrier
between the particles and form a bridge between adjacent particles.
Example: Dispersion of bismuth subnitrate in water. As bismuth particles
possess large positive charge. Because of the repulsive force between adjacent
particles, the system remains in deflocculated state. The addition of small amount
of monobasic potassium phosphate (KH2PO4) to the suspension causes the
adsorption of the negatively charged phosphate anion on positive charged bismuth
particles. As a result repulsive force start to decrease and attractive force start
to form. The particles then can come closer to form aggregates or flocs.
b. Surfactants: They are also used for flocculation of suspended particles. They
also act as wetting agents to achieve dispersion. Both ionic surfactants (sodium
lauryl sulfate) and non ionic surfactants (Tweens) are used.
c. Polymers: They are high molecular weight compounds. These agents also act as
flocculating agents. In polymers, part of the chain is adsorbed on the particle surface
while remaining parts extruding into the dispersion medium. This lead to formation of
flocs.
3. Thickeners:
They are added to increase the viscosity. Therefore the particles remain suspended for
long time.
a.Acacia, tragacanth, sodium alginate: They are all natural
polysaccharides.
b. Methyl cellulose, sodium carboxymethyl cellulose: They are all semisynthetic
derivatives. Methyl cellulose is used in concentration of
0.5 to 2% while sodium carboxymethyl cellulose is used in the concentration of
0.25 to 1%.
c. Others: Bentonite, Aluminium hydroxide, carbomer, colloidal
silicone dioxide.
4. Preservatives:
• They are added to prevent microbial growth.
• Example: Benzoic acid, Propylene glycol. Disodium EDTA
5. Coloring agent
• They are used to improve elegance. They are used to improve the attractiveness by
the patients.
• Plant colours are most widely used for oral suspension.
• Example: Titanium dioxide, Brilliant blue, Tartrazine.
6. Sweetening and Flavouring agent:
• They are also added in oral suspension. Sweeting agent are used to masking the
bitter drug particles.
• The following sweetening agent used in suspension preparation:
i. Bulk sweeteners- Sugar: xylose, ribose, glucose, mannose, galactose, fructose
Sugar alcohol: Sorbitol, xylitol, mannitol, glycerin
ii. Artificial sweetening agent- Sodium cyclamate, sodium saccharin, aspartame
• Sweetening agent alone not capable to complete taste masking of unpleasant drugs
therefore, a flavouring agent is incorporated to increase patient compliance.
• Ex. Cherry syrup, clove oil, cinnamon oil, lemon oil, nutmeg oil
Preparation of suspension:
⚫ Different steps follows during the preparation of suspension are-
Grinding of insoluble material with vehicle containing wetting agent to
get smooth paste

Dissolve soluble ingredients in some portion of vehicle and add into

above step to get slurry

Transfer the slurry to graduates

cylinder Rinse mortar with some part of

vehicle

Add suspending agent or Flocculating agent if any by

mixing into
vehicle
 METHOD OF PREPRATIONS

1. General Methods
a) Precipitation method
i. Organic solvent method
ii. Precipitation effected by changing the pH of the medium
iii. Double decomposition
b) Dispersion method
i. Small scale (laboratory): Using mortar & pestle
ii. Large scale (industry): Using colloid mill

2. Extemporaneous method
a. From dry powders and granules for reconstitution
b. From oral solid dosage form

3. Mechanism involved
a) Controlled flocculation
b) Structured vehicle
 Emulsion
⚫ Emulsion is a biphasic system consisting of two immiscible liquids where one
liquid (dispersed phase) contains minute droplets is uniformly
distributed into the another aqueous (continuous phase) by using emulsifying
agent. The substance that are used to stabilizes a emulsion is called an
emulsifier or emulgent The particle size of dispersed phase range from 0.1 to 100
um.
⚫ Emulsion being a heterogeneous system are thermodynamically unstable and thus a
third substance, the emulsifier is added to stabilize the system.
 Advantag
1.
es:
Medicines having an unpleasant taste and odour can be made more palatable for
oral administration in the form of an emulsion. e.g., castor oil, cod-liver oil
etc.
2. Emulsion provides protection against drugs which are prone to oxidation or
hydrolysis.
3. Various external preparations such as, creams, lotion and foam aerosols are
formulated in emulsion.
4. The sterile stable intravenous emulsions containing fats, carbo- hydrates and
vitamins can be administered to the patients who are unable to take them
orally.
5. Emulsions improves the absorption of oils when taken internally.
6. Nowadays radio opaque emulsion are used as diagnostic agent in X- ray
examination.
 DISADVANTAGES
1. Emulsion need to be shake well before use
2. Storage conditions may affect emulsion stability
3. They are bulky, difficult to transport and prone to container breakages.
4. They are prone to microbial contamination which can lead to cracking

CLASSIFICATION OF EMULSION:

There are different type of emulsions

⚫ 1. Oil-in-water emulsion (o/w):
The emulsion in which dispersed phase is oil and continuous phase is water are called
as oil-in-water emulsion. Example: Milk in which liquid fat globules are dispersed in
water. These type of emulsions are also called aqueous emulsion. They are mostly preferred
in case of oral use. The o/w type emulsion is also used to prepare creams, lotions,
liniments due to non greasy nature and easily removed from body.
⚫ Water-in-oil Emulsion (w/o):
The emulsion in which dispersed phase is water and continuous phase is oil are called
as water-in-oil emulsion: These emulsion are also known as oil emulsions. Example:
Butter and cold cream. The ability to leave the ski oily makes the w/o emulsion an ideal
base for dry/sensitive skin treatments. This emulsion is greasy in nature.
3. Multiple emulsion:
They are also known as "double emulsion" or "emulsion-within- emulsion".
Multiple emulsions may be of the 'oil-in-water-in-oil (O/W/O) type or "water-in- oil-in-
water (W/O/W) type Oil-in-water-in-oil (O/W/O) emulsions is an emulsion in
which o/w emulsion is dispersed in another oil phase while water-in- oil-in- water
(W/O/W) emulsions is an emulsion in which w/o emulsion is dispersed another
aqueous phase. They are called multiple emulsion because the droplets of one liquid
are dispersed in droplets of a second liquid, which is further dispersed in the
dispersion medium. These type of emulsion are prepared to prolong the release of drugs
Multiple emulsions have more complex structure. They are widely used to enhance
bioavailability and for controlled or targeted drug delivery.
4. Microemulsion:
• Microemulsion is defined as clear, transparent emulsion consisting of globules of less
than 0.1 um in diameter. These type of emulsion are preferred due to high capacity
of microemulsions for drugs. Due to high capacity, microemulsion are
fix choice for pharmaceuticals.
• Microemulsions are thermodynamically stable as to conventional emulsion. They
are prepared by dispersing oil in an aqueous surfactant solution and then
cosurfactant is added.
• Microemulsion act as potential drug carrier system for oral, topical and
parenteral administration.
 Identification test for emulsion:
The following tests are done to distinguish between o/w and w/o emulsions:-
1. Dilution test:
The emulsion is diluted with water. In case the emulsion remains stable after its
dilution, it is o/w emulsion. The w/o emulsion breaks on its dilution with water but
remains stable when diluted with oil.
2. Dye test:
The scarlet red dye is mixed with the emulsion. Place a drop of the emulsion on a
microscopic slide, cover it with a cover-slip, and examine it under a microscope. If the
disperse globules appear red and the 'ground' colourless, the emulsion is o/w type.
The reverse condition occurs in w/o type emulsion i.e., the disperse globules appear
colourless in the red 'ground'.
3. Conductivity test:
Water is a good conductor of electricity, whereas oil is non-conductor of electricity. The
conductivity test can be performed by dipping a pair of electrodes connected through
a low voltage bulb in the emulsion. If the bulb glows on passing the electric current, the
emulsion is o/w type, because water is in the continuous phase. In case the bulb does
not glow, the emulsion is w/o type, because oil is in the continuous phase.
 4. Fluorescence test : Certain fixed oils possess the physical property of
fluorescing in the presence of ultraviolet radiation. On microscopic observation of
emulsion under ultraviolet radiation, the whole field fluorescence indicates that oil is
present in continuous phase (w/o type emulsion) and the droplets fluorescence
indicates that oil is present in dispense phase (o/w type emulsion)

Formulation of emulsion
(A) Emulsifying Agents:
⚫ The emulsifying agents reduce the interfacial tension between two phases i.e., oily
phase and aqueous phase and thus make them miscible with each other and
form a stable emulsion. Emulsifying agents are also known as emulgents or
emulsifiers.
⚫ There are large number of emulsifying agents which are available to prepare a stable
emulsion. But it is very difficult to select a proper emulsifying agent for the
development of a stable emulsion. No single emulsifying agent possesses all the
properties required for the preparation of stable emulsion. Therefore,
sometimes it becomes necessary to use two or more than two emulsifying
agents instead of one, to prepare a stable emulsion.
⚫ Griffin devised a useful method for calculating balanced mixtures of
emulsifying agents to provide a particular type of emulsion. It is called the
Hydrophile Lipophile balance or HLB method. Every emulsifying agent is
given a number on HLB scale, which is divided into 18 units. Emulgents with
higher numbers (8-18) indicates hydrophilic properties and produces o/w type
emulsions. Emulgents with lower numbers (3-6) represents lipophilic
properties and produces w/o type emulsions. The following table indicates the
HLB values and applications of emulsifying agents:-
Sr. Name of the HLB Applications
No. Emulsifying Agent Value
1 Acacia 8 Emulsifying agent o/w

2 Glyceryl monostearate 3.8 Emulsifying agent w/o

3 Sorbitol monostearate 4.7 Emulsifying agent w/o

4 Polysorbate 20 16.7 Solubilizing agent

5 Polysorbate 60 14.9 detergent

6 Polysorbate 80 15 Solubilizing agent

An ideal emulsifying agent should possess the following
properties:

⚫ An ideal emulsifying agent should possess the following properties:

1. It should be capable of reducing the interfacial tension
between the two immiscible liquids.
2. It should be compatible with other ingredients of the
preparation.
3. It should be non-toxic.
4. It should be capable to produce and maintain the required
con-sistency of
the emulsion.
5. It should be chemically stable.
6. It should be capable of keeping the globules of dispersion
liquid distributed indefinitely throughout the dispersion
medium.
Classification of Emulsifying Agents
⚫ Emulsifying agents may be classified as follows:-
1. Natural emulsifying agents from vegetable sources:
⚫ These are carbohydrates which includes gums and mucilaginous substances. They
are anionic in nature and produce o/w type emulsions. The emulsions
prepared from these emulsifying agents need suitable preservative to preserve them
because the carbohydrates act as a medium for bacterial growth. The
following are some of the emulsifying agents belonging to this class:-
(a) Acacia :
⚫ Acacia is considered to be the best emulsifying agent for the preparation of
emulsion for internal use.
⚫ Emulsions prepared with gum & acacia are attractive in appearance, quite
palatable and relatively stable over a wide range of Ph (2 to 10 ) The emulsion
prepared with gum acacia usually have low viscosity therefore creaming takes place
rapidly
(b) Tragacanth :
Tragacanth alone is rarely used as an emulsifying agent because it produces very
coarse and thick emulsion. The appearance and stability of the emulsion can be
improved by passing the emulsion through a homogenizer. A stable emulsion can
also be produced if tragacanth is used along with gum acacia as emulsifying agent.
(c) Agar :
It is not a good emulsifying agent, as it forms a very coarse and viscous
emulsion. It is used as emulsifying agent by preparing 2% mucilage, by
dissolving in boiling water and cooled to 45°C.
(d) Pectin :
It is used as emulsifying agent by preparing 1% mucilage in water. It is
incompatible with alkalis, strong alcohol, tannic acid and salicylic acid.
(e) Starch :
Starch mucilage is rarely used because it forms very coarse emulsions. It is
generally used to prepare enemas.
2. Natural emulsifying agents from animal sources:
(a) Wool fat :
It is generally used in emulsion which are meant for external use. It produces o/w
type emulsions and can absorb about 50% of water.
(b) Egg yolk :
It is mainly used in extemporaneous preparations meant for internal use because it get
spoiled during transportation. The emulsion prepared with egg yolk require proper
preservation and storage in a refrigerator. It is used as emulsifying agent in the
concentration of 12-15%
(c) Gelatin:
It is used in the concentration of 1% as emulsifying agent. It is mainly used for the
emulsification of liquid paraffin. The emulsion prepared with gelatin is quite white and
have an agreeable taste. But it needs. But it needs proper preservation because emulsion
are prone to bacterial growth.
(3) Semi- synthetic polysaccharides:

(a) Methyl cellulose:

It is a synthetic derivative of cellulose. It is widely used as suspending, thickening and
emulsifying agent in the concentration of 2%. It is commonly used for
emulsification of mineral and vegetable oils, but get precipitated in the presence of large
amount of electrolytes.
(b) Sodium carboxymethyl cellulose:
It is used as an emulsion stabilizer in the concentration of 0.5 to 1.0%. It is soluble
in both cold and hot water
(4) Synthetic emulsifying agents :
The anionic, cationic and non- ionic surface active agents are used as
emulsifying agents.
(a) Anionic:
Various alkali soaps, metallic soaps, sulphated alcohols and sulphonates are used as
anionic emulsifying agents. Soap emulsions are used for external application.
Sodium lauryl sulphate is commonly used as emulsifying agent among the sulphated
alcohols. It produces o/w emulsions.
(b) Cationic:
The quaternary ammonium compounds, such as benzalkonium chloride,
benzethonium chloride, cetrimide are used as cationic emulsifying agents.
Cationic surface active agents bear positive charge on them. They are mainly used in
the preparations meant for external use, such as, skin lotions and creams.
(c) Non-ionic:
The glyceryl esters, such as glyceryl monostearate, sorbitan fatty acid esters such as
sorbitan monopalmitate are commonly used non-ionic surface active agents. They
are widely used in the preparation of pharmaceutical emulsions, because emulsions
prepared with non-ionic surfactants remain stable over a wide range of pH changes.
(5) Alcohols:

(a) Carbowaxes :
⚫ These are mainly used in the preparation of ointments and creams.
Carbowaxes having molecular weight between 200-700 are viscous, light
coloured, hygroscopic liquids. Whereas carbowaxes with molecular weight 1000
and above are wax like solids. A product of desired consistency can be
prepared by using right type of carbowaxes or a mixture of carbowaxes.
(b) Cholesterol :
⚫ In this category, cetyl alcohol, stearyl alcohol, cholesterol and glyceryl
monostearate are used to stabilize the emulsion. They are used only with some other
emulsifying agent.
(c) Lecithin's:
⚫ Lecithin's which forms w/o emulsion, is rarely used as an emulsifying agent
because it darkens in colour when exposed to light and gets easily oxidised.
2. Preservatives:
The bacteria, fungi and moulds may cause unpleasant taste, odour and
discoloration of emulsion. Preservatives are added to inhibit their growth.
Example: benzoic acid (0.1-0.2%), methyl paraben and propyl paraben (0.1-0.2%),
chloroform (0.25%), Chlorocresol (0.1%), cetrimide (0.002-0.01%) and phenyl
mercuric nitrate (0.004- 0.01%).
3. Antioxidants:
Sometime oxidation occurs either by oxidation or by enzymes produced
by microorganism. This can be avoided by adding antioxidants such as tocopherol,
gallic acid, ascorbic acid and propyl gallate.
The following are some of the qualities of an ideal anti-oxidant:-
(1) It should be readily soluble or dispersible in the medium.
(2) It should be effective in low concentration.
(3) It should be non toxic.
(4) It should be non irritant.
(5) It should be compatible with other ingredients of emulsion.
(6) It should be colorless, odourless and tasteless.
4. Colouring agent, Sweetening agents and Flavouring agent:
They are also incorporated in the formulation of emulsion. A combination of
flavouring and sweetening agent provides greater palatability to emulsion.
Stability of emulsion:
Emulsion is said to be stable if it remains as such after its preparation, i.e., the
dispersed globules are uniformly distributed through- out the dispersion medium during its
storage. The emulsion should be chemically stable and there should not be any bacterial
growth during its shelf life.
The following three changes usually occurs during the storage of emulsion:-
1. Cracking
2. Creaming
3. Phase inversion
4.Cracking : Cracking means the separation of two layers of disperse and continuous
phase, due to the coalescence of disperse phase globules which are difficult to redisperse by
shaking. Cracking may occurs due to the following reasons:-
(i) By addition of emulsifying agent of opposite type :
Soaps of monovalent metals produce o/w type emulsions whereas soaps of diva lent metals
produce w/o type emulsions. But the addition of monovalent soap to a divalent soap emulsion
or a divalent soap to a monovalent soap emulsion leads to cracking of emulsion.
(ii)By decomposition or precipitation of emulsifying agents: When an acid is added to
an alkali soap emulsion (turpentine liniment), it causes the decomposition of an emulsifying
agent and thus leads to cracking of an emulsion.
Similarly, when sodium chloride is added to sodium or potassium soap emulsion, it leads to the
precipitation of emulsifying agents and thus cracking of emulsion take place.
(iii) By addition of a common solvent :
⚫ When a solvent is added to an emulsion which is either miscible with or
dissolve the dispersed phase. the emulsifying agent and continuous phase, there
is formation of one phase or a clear solution. This leads to cracking of an
emulsion. For example, addition of alcohol to turpentine liniment leads to the
formation of clear solution because turpentine oil, soft soap and water are
soluble in alcohol.
(iv) By microorganisms:
⚫ If emulsions are not stored properly, they may develop bacterial and mould
growth. This may lead to destruction of emulsifying agent and cause cracking of
emulsion. Therefore, it is desirable that all emulsions which are required to be
stored for long time should be suitably preserved.
(v) Changes in temperature:
When emulsions are stored for a long time, an increase in temperature may reduce the
viscosity of the emulsion and encourage creaming. When emulsions are stored at a very
low temperature, freezing of its water content into ice and subsequent melting of the ice
and shaking may reform the emulsion.
(vi) By creaming:
A creamy emulsion is more liable to crack than a homogenous emulsion. it is
therefore, necessary to take steps to retard creaming as far as possible
2) Creaming:
⚫ Creaming may be defined as the upward movement of dispersed globules to form a
thick layer at the surface of the emulsion. Creaming is a temporary phase because it
can be re-distributed by mild shaking or stirring to get again a homogenous
emulsion.
⚫ As far as possible creaming of an emulsion should be avoided because it may lead
to cracking with complete separation of two phases.
⚫ According to Stoke's law, the rate of creaming depends on the number of factors
which can be explained by the following equation:-

⚫ where
⚫ V = rate of creaming
⚫ r = radius of globules
⚫ d1 = density of dispersed phase
⚫ d2= density of continuous phase
⚫ g = gravitational constant
⚫ eta = Viscosity of the dispersion medium
(1) Radius of globules:
The rate of creaming is directly proportional to the radius of the globules. Larger the size of
the globules, the more will be creaming and smaller the size of the globules, lesser will be
creaming. The small globules will rise less quickly than large globules. Hence,
creaming can be reduced by reducing the size of globules by passing the emulsion through a
homogeniser.
(2) Difference in density of disperse phase and continuous phase :
The rate of creaming depends upon the difference between the densities of the disperse
phase and continuous phase. Greater the difference, more will be the creaming. This
difference can be reduced but it is not desirable because it is not required therapeutically.
(3) Viscosity of the dispersion medium :
The rate of creaming is inversely proportional to the viscosity of the dispersion medium. The
viscosity can be increased by adding tragacanth and methyl cellulose. But too much viscosity
is undesirable because it may become difficult to re-disperse the material which have settled
at the bottom. Moreover, is difficult to pour the emulsion from the container.
(iv) Storage condition:
The emulsion should be stored in a cool place because the rise in temperature reduces the
viscosity which may Read to creaming. The freezing should be avoided because it may lead
to cracking.
3. Phase inversion :
Phase inversion means the change of one type of emulsion into the other type i.e., oil
in water emulsion changes into water in oil type and vice versa. It may be due to
following reasons:-
(i) By the addition of an electrolyte
(ii) By changing the phase-volume ratio
(iii) By temperature change
(iv) By changing the emulsifying agent.
The phase inversion can be minimised by keeping the concentration of disperse phase
between 30 to 60%, storing the emulsion in a cool place and by using a proper
emulsifying agent in adequate concentration.
Preparation of emulsion:
The formulation of emulsion are related to the selection of the aqueous phase, oil phases
and type of emulgents and their relative proportions. The ingredients used in the preparation
of an emulsion should be chemically compatible. The ingredients should pass the
toxicological tests
a. Selection of lipid phase
The ingredients used for oil phase emulsion are: Mineral oils, Petrolatum,
Polyethylene waxes, Vegetable oils, Animal fats, Lanolin, Substituted silicones, Plant waxes
(Candellia) and Animal waxes (Beeswax).
The lipids are prone to oxidation due to chemical changes. The Emulsions prepared for
topical purpose should possess a good "feel" but the emulsions containing oil leave oily residue
on the skin. Therefore, the optimum volume of oil should be selected.
b. Selection of aqueous phase:
Mostly water is used as aqueous phase. The optimum ratio of aqueous phase should be
selected.
 C. Selection of emulsifying agents / Emulsifiers/Emulgents:
⚫ The selection of emulsifying agents are based on the site of application i.e. either
for internal or external use. The examples of emulsifying agents are
Synthetic emulsifying agent / Surface active agents (SAA) / Surfactants,
hydrophilic colloid and finely divided solids. Non ionic and water soluble
emulsifying agents are selected for internal use while ionic and non ionic
emulsifying agents are selected for external use. The natural gums growth. Finely
divided solids are used frequently for external purposes such as lotion or
cream.
⚫ Exhibit some type of incompatibility or instability and also cause microbial

After selection of all components, on small scale, the basic method used in
preparation of emulsion are
1. dry gum method
2. wet gum method
3. bottle method
1. Dry gum method:
The continental method is used to prepare primary emulsion from oil, water, and a
gun type emulsifier (usually acacia). It is also called 4:2:1 method because 4 parts
oil, 2 part water, and 1 part emulsifier is used. Mortar and pestle is used to prepare
emulsion.

Steps involved in preparation of emulsion are:

 1 part gum is levigated or triturated with the 4 parts oil in a dry mortar

Now add 2 parts water all at once

Triturate is continuously until "cracking" sound is

produced Clicking

At this time the primary emulsion will be creamy white

Then add more quantity of water to the primary

emulsion

Solid substances, if any, are added as a solution to the

primary emulsions

Oil soluble substance, in small amounts, may be incorporated directly into the primary
emulsions

Any substance such as alcohol should be added near to the end of the process to avoid
breaking the emulsion
2. Wet gum method:
⚫ It is also called as english method
⚫ The proportions of oil, water, and emulsifier in wet gum method are the
same as m dry gum method i.e (4:2:1), but the steps and techniques of
mixing are not same In this method, 4 part oil. 2 part water and 1 part
gum is used. English method is more difficult but it produce more
stable emulsion
Steps involved in preparation of emulsion are
I part gum is levigated or triturated with the 2 parts water to form a mucilage

Add 4 parts oil slowly during trituration

Continuously triturate to form the primary emulsion

Add other ingredients, if any, as in the continental

method

Transfer the primary emulsion to graduated cylinder

Make the final volume with water.

Bottle Method:
It is also known as Forbes Method
This method is used to prepare emulsions of volatile oils, or substances
having very low viscosities. It is not suitable for very viscous oils.

1 part gum or powdered acacia is placed in a dry bottle G

2 parts of oil are added

Shake the mixture thoroughly after capping

A volume of water (approximately equal to that of the oil) is added in

portions Again shake the mixture thoroughly until the primary emulsion is

formed Dilute it with proper volume of water

Others methods:

⚫ Various blenders and homogenisers are used for preparing emulsions. Hand
homogeniser, Silverson mixer homogeniser and colloidal mill are some of
the homogenisers which are used for the preparation of
emulsions. These homogenisers are based on the principle that the
large globules in coarse emulsion are broken into smaller
globules by passing them under pressure through a narrow orifice.
⚫ A coarse emulsion is prepared in a mortar which is then transferred into hand
homogeniser. The emulsion is passed through a homogeniser many a times
till an emulsion of desired satisfaction is produced. The colloidal mills
are used to produce a very fine emulsion having globule size less than
one micron on a large scale manufacture.
Hand homogeniser :
The homogeniser is hand operated and the coarse emulsion is passed though a fine
orifice. The emulsion is placed in the hopper of the homogeniser. The up and down
movement of the handle causes coarse emulsion to draw in through inlet value and
pass through homogenising value. In this way the emulsion is forced to pass
through the fine orifice. The oil globules are broken into fine globules of uniform
size.
Silverson mixer homogeniser :
⚫ It consists of an emulsifier head which is covered with fine meshed
stainless steel sieve. The emulsifier head consist of a number of
blades which rotate at a very high speed in order to produce a powerful
shearing action. The blades are rotated by using an electric motor
fitted at the top.
⚫ The emulsifier head is placed in a vessel containing immiscible liquids, in
such a way that it should get dipped into it. When the motor is started,
the liquids are sucked through the fine holes and the oil is reduced
into fine globules due to the rotation of the blades.
⚫ So a fine emulsion is produced which is then expelled out. expulsion of
the mixture set up a pattern of circulation.
STORAGE OF EMULSIONS:

Containers : The emulsion should be packed in containers having an adequate air space
above the emulsion, so as to permit adequate shaking before its use. The emulsions
which are meant for internal use, should be packed in comparatively wide mouth bottle
so that it is easy to remove it without any difficulty. Metallic closures should be
avoided. Wide mouthed amber glass bottles are most appropriate for the storage of
emulsion.

Labelling : A secondary label " Shake well before use" is required to be fixed on
the bottle.

Storage: An emulsion should be stored in air tight container, protected from light, high
temperature or freezing. The emulsions are required to be stored in a cool place.
EVALUATION OF LIQUID ORALS OFFICIAL IN PHARMACOPOEIA
1. Light transmission test:
⚫ In this method, a light transmittance meter is used in which light is passed
through a syrup sample to be tested for colour. The percent of light transmission
is compared to light transmission rates set for different grades.
2. Visual inspection:
The final products are carefully evaluated for purity and appearance. It should be clear
and free from any precipitate. Discoloration or cloudiness of solutions may indicate
chemical degradation or microbial contamination.
3. Taste and Odour: They are evaluated by panel of taste sensitive individuals

4. pH measurement:
The measurement of pH is also very important step in the Quality control testing. In this
method, pH meter is used. A piece of pH paper is dipped into the sample. The paper is
impregnated with chemicals that change colour which is compared to a chart given with
the paper to examine the pH of the sample. The pH value of a solution is also determined
potentiometrically by means of a glass electrode and reference electrode
5. Sucrose concentration (in case of syrup):
This is evaluated by using HPLC and UV- spectroscopy methods.

6. Assay:
The assay of oral liquids has to be done to detect API by using suitable analytical method
to produce good finished pharmaceutical. This test is one of the most important tests that
determine the strength or content of the API.

7. Determination of alcohol content (in case of elixirs):

Distillation method is used determine alcohol content. The determination of alcohol unless
otherwise specified in the individual monograph. It is suitable for examining most fluid
extracts and tinctures and elixirs provided the capacity of the distilling flask is sufficient
(commonly two to four times the volume of the liquid to be heated) and the rate of
distillation is such that clear distillates are produced. Cloudy distillates may be clarified by
agitation with talc or with calcium carbonate. And filtration is done. After which the
temperature of the filtrate is adjusted and the alcohol content determined from the specific
gravity. During all manipulations, take precautions to minimize the loss of alcohol by
evaporation.
8. Viscosity measurement:
Different types of viscometers such as U tube viscometer, Capillary viscometer
method, Rotating viscometer, Cone-plate viscometers and Spindle viscometers are
used to determine viscosity.

9. Stability studies:
Stability studies at various different temperature and pH are evaluated

10. Uniformity of Mass:

According to British Pharmacopoeia (BP), this test is applicable for single- dose
preparations that are solutions or emulsions; single-dose powders and granules for
syrups, oral solutions, oral suspensions; and single-dose powders for oral drops.
For this test weigh individually the contents of 20 dosage units taken at random,
emptied as completely as possible, and determine the average mass.
As stated by BP, for single-dose preparations that are solutions or emulsions not more than
2 of the individual masses deviate by more than 10 percent from the average mass and none
deviate by more than 20 percent.
For single-dose powders and granules for syrups, oral solutions, oral suspensions and
single-dose powders for oral drops according to BP not more than 2 of the individual
masses deviate from the average mass by more than the percentage deviation and none
deviate by more than twice that percentage.
 Average mass (mg) Percentage deviation
Less than 300 10
300 or more 7.5

11. Uniformity of Volume:

• According to Indian Pharmacopoeia (IP), this test is suitable for oral liquids and oral
Suspensions of viscous preparations.
• For this test sample of 10 filled containers is randomly selected and determine the
weight of the contents of each container. The net volume is calculated by pouring, the free-
flowing liquids into calibrated volume measures of the appropriate size The average net
volume of the contents of the 10 containers should not less than
the labelled amount, and the net volume of the contents of any single containers
should not less than the percentage deviation. If this requirement is not met,
determine the volume of the contents of 10 additional containers.

Net volume (ml) Percentage deviation (%)

50 or less 9

More than 50 but not more than 200 4.5

More than 200 but not more than 300 3

⚫ 12. Phase Separation: This test is applicable for pharmaceutical emulsion.
The rate and degree of phase separation in an emulsion can be easily
determined by keeping a certain amount in a graduated cylinder and measuring
the volume of separated phase after definite time intervals.
⚫ 13. Sedimentation volume: This test is applicable to pharmaceutical
suspension. It is the ratio of the ultimate volume of sediment (V_{u}) to the
actual volume of sediment (V_{0}) before settling.
⚫ F = V_{u} / V_{O}
⚫ The value of F gives a knowledge about the physical stability of
the suspension.
⚫ (1) F = 1 indicates - no sedimentation and no clear supernatant
⚫ 2) F = 0.5 indicates -50% of the total volume is occupied by sediment
⚫ 3) F > 1 indicates- Sediment volume is greater than the actual volume due to
formation of network of flocs or floccules in suspension which are fluffy and
loose
⚫ Degree of flocculation (B):
⚫ This test is applicable to pharmaceutical suspension. It is the ratio of the
sedimentation volume in case of flocculated suspension (F) to the
sedimentation volume in case of deflocculated suspension, ( F∞ )
beta = F / F ∞

⚫ β is a quantitative & more fundamental parameter. The minimum value of β is

1.when sedimentation volume of flocculated suspension is equal to the
sedimentation volume of deflocculated suspension.
15. Zeta Potential:
This test is applicable for pharmaceutical emulsion and suspension. It can be
determined by electrophoretic mobility measurements i.e. by observing the
movement of droplets under the influence of an electric current.

16. Microbiological Test:

The tests allow quantitative estimation of mesophilic bacteria and fungi that may
grow under aerobic conditions. Membrane filtration and plate count methods are
used for determination of total viable aerobic count. Growth of colonies indicates
the presence of microorganism. This test is done to evaluate the preservatives
efficiency