Principal K. M.

Kundnani College of Pharmacy

(GOVT. AIDED, PCI APPROVED, ACCREDITED BY NBA & AFFILIATED TO UNIVERSITY OF MUMBAI)
Plot No. 23, Jote Joy Building, Rambhau Salgaonkar Road, Cuffe Parade, Mumbai-400005.

Biphasic Liquid Dosage form

Mr. Vaijnath
Rathod
Assistant Professor
 Learning Objectives
 Learner would be able to understand :

1. What do you mean by Suspension & Emulsion ?

2. What are the method of preparation of Suspension & Emulsion ?
3. Classification of suspension & emulsion?
4. Advantages & Disadvantages of suspension & emulsion ?
5. Stability problems and method to overcome?
 Content

• Defination of Suspensions.
• Advantages & disadvantages Suspension & Emulsion
• Classification
• Methods of preparation of Suspension and Emulsion
• Stability problem and method to overcome
 Introduction
Defination :
 Liquid preparations having two phases are termed as biphasic liquids.
These preparations have dispersed phase and dispersion medium.

Emulsion: These are biphasic liquid preparations of two immiscible liquids,

with one liquid dispersed in the other liquid in the form of globules.

Suspensions: These are biphasic liquid preparations in which the finely

divided drug particles are uniformly dispersed throughout the vehicle.
 Suspensions

 Are biphasic liquid preparations containing finely divided 0.5-3

micron diameter solid drug particles dispersed or suspended
throughout a liquid or semisolid vehicle.
 Suspensions are heterogeneous system consisting of 2 phases.
 Ideal properties of suspension

 The solid drug particles should not sediment. On slightly shaking of the
suspension container, the sediment should immediately redisperse.
 The particles should not sediment to form cake.
 The suspension should be viscous enough to allow its easy pouring.
 The suspension should be chemically stable.
 The suspension should be palatable for oral administration, whereas, for
external applications they should not contain gritty particles.
Advantages of suspensions
1. It is easy to formulate drugs having large doses, in the form of
suspension, than the solid dosage forms like tablet and capsules.
2. It is easy to swallow for children and geriatric patient.
3. Bioavailability is greater.
4. Insoluble drugs can be formulated in the form of liquid dosage
forms.
 Disadvantages of suspensions

1. Accuracy of dosage is less reliable.

2. Dispersed drug particles may adsorb added flavors, colours, and
preservatives making it difficult to formulate a suspension.
3. The rate of absorption is slower than the solution dosage forms.
 Classification of suspensions:

1. Suspensions are classified according to route of administration;

A. Suspensions for oral use:
 These are administered by oral route and are convenient for Paediatric and geriatric
patients who have difficulty in swallowing solid dosage forms.
 The formulation of oral suspensions contains sweetening and flavoring agents to
enhance their palatability.
 Suspension for oral use are also called as "mixtures".
 Eg: Magnesium trisilicate mixture
B. Suspension for topical use :
 These suspensions are meant for external use and applied on skin without
rubbing.
 They are often referred as 'lotions’.
 Eg: Calamine lotion.

C. Suspension for Nasal use :

 These are termed as inhalations containing one or more volatile oils dispersed in
water.
 A distributing agent such as light magnesium carbonate is used in these
suspensions to adsorb the oil.
 Eg: Menthol and eucalyptus oil inhalation
D. Suspension for ophthalmic use :
 Drugs that are insoluble or unstable in water are formulated as
suspensions for ophthalmic use.
 These suspensions should be sterile, isotonic and suitably viscous for
retaining in the eye.
 Eg: prednisolone acetate ophthalmic suspension.

E. Suspension for parenteral use:

 Parenteral suspensions are formulated to provide prolonged release.
 The particle size of suspended drug should be such that it can easily pass
through the needle of the syringe.
 These suspensions should be sterile.
2.Suspensions are classified according to the particle size of the dispersed
phase:

A. Colloidal suspension: have particle size between 1nm- 500nm. These are
therapeutically more effective than coarse suspensions.
B. Coarse suspensions: Particle size more than 1 micron.
3.Suspensions are classified according to the properties of dispersed solid into
four types;
A. Suspensions containing diffusible solids:
 Many insoluble powders are light and easily wettable. They readily mix with water and
on shaking diffuse evenly through the liquid for sufficiently long time, enough to ensure
uniform withdrawal of each dose. Such substances are known as diffusible or
dispersible solids.
 Eg: light kaoline, Light magnesium carbonate
B. Suspensions containing indiffusible solids:
 Indiffusible solids do not remain evenly distributed in the vehicle long enough to
ensure uniformity of dose and hence require suspending agent.
 Eg: Aspirin, chalk.
C . Poorly wettable solids:
 Some substances are insoluble in water and have poor wettability with water.
 While preparing aqueous suspensions of such substances, some particle form lumps
in the liquid which are difficult to disperse while other remain on the surface and
become attached to the upper part of the container.

D. Suspensions containing precipitate forming liquids:

 Certain liquid preparations contain resinous matter that precipitates out when added
to water. They are insoluble in water and form indiffusible precipitates in the
presence of salts.
4. Suspensions are classified according to properties of dispersed phase
into two types :
A. Flocculated suspensions:
 A loosely bound structure of particles is called a flocculate or floccule.
 The flocculated particles tend to sediment at rapid rate, because each unit is
composed of many individual particles.
 The volume of final sediment is large and easily redispersed by moderate
agitation.
 In flocculated suspensions, the supernatant becomes clear.

B. Deflocculated suspensions:
 In this system, the dispersed particle remain as discrete units and the rate of
sedimentation depends on the size of each unit.
 The rate of settling is slow.
 The supernatant of deflocculated system remains cloudy after shaking for an
appreciable time due to very slow settling rate.
Methods of preparation of suspensions:
 Suspensions are prepared by two methods;
1. Dispersion method
2. Precipitation method
1. Dispersion method:
Method of preparation on laboratory scale:
 Dispersion method is used for preparing suspension containing
diffusible, indiffusible drugs and drugs with good or poor wettability.
It involves the following steps;
a. Taring of container:
 A tared container in used because complete transfer of prepared
suspension from a measuring cylinder is difficult.
 A quantity of water equivalent to a final volume of the preparation is
measured using a measuring cylinder and transferred to a suitable
container.
 The level of water is marked on the container and this marking is used
for making up the final volume. This is known as Taring of container.
b . Size reduction:
 Particle size reduction is the first step in the preparation of any suspension.
Particle size reduction is achieved by triturating the drug using a mortar and
pestle. And subsequently sifting throw sieve no.80.
 The fine drug powder obtained is used for further processing.
C . Dispersion of drug into vehicle:
 The powdered drug particles get uniformly dispersed in the vehicle. There are
four possibilities;
i. The drug is diffusible, having good wettability.
ii. The drug is indiffusible
iii. The drug is poorly wettable .
iv. The drug is a precipitate forming liquid.
2. Precipitation methods:
 These method is less widely used to prepare suspensions.
 The drug is suspended in a vehicle by precipitating it from its solution.
 The method is useful for drugs which are required to be sterile but are unstable on
heating or irradiation.
This method is divided into three types;
 Precipitation with organic solvents
 Precipitation with pH change of media
 Precipitation with chemical reaction
 Formulation of suspensions:
1. Drug:
• The drug should be insoluble in the vehicle with good chemical stability and
wettability.
• It should have fine particle size and uniform particle size distribution.
• The drug should be present ion only one polymorphic form, because different
polymorphic form have different solubility.
2. Wetting agents:
• Poorly wettable drug particles have air adsorbed on their surface which prevents
their dispersion in the vehicle.
• To ensure adequate wetting, the adsorbed air should be displaced from the surface of
the drug. this is achieved by use of wetting agents.
The most widely used wettings agents are;
1. Surface active agents.
2. Hydrophilic colloids.
3. Solvents

4. Surface active agents:

• Surfactants with HLB value between 7 and 9 would be suitable for use
as wetting agents.
• Surfactants are capable of displacing the adsorbed air and occupying
its place, thereby reducing the surface tension and this improves the
wettability of drug particles.
• Eg: tweens and spans.
2. Hydrophilic colloids:

• These act as protective colloids by coating the poorly wettable drug

particles with a multimolecular layer.
• Eg: Acacia, bentonite.

3. Solvents:
• The solvent penetrates the loose agglomerates of powder and
displaces the air from the pores. This enables wetting of the drug
particles.
• Eg: Alcohol, glycerol.
 3.Suspending agent/thickening agents or viscosity
modifiers:

 A suspending agent is required to enhance viscosity of suspension and delay its

sedimentation.
 A ideal suspension should be viscous during storage, so that suspended particles settle
very slowly.
 At the same time, on moderate shaking, the viscosity should decrease sufficiently so that
the product shall be poured easily form the container.

The suspending agents can be classified into following types as shown below;
 Natural polysaccharides

1. Acacia:
 This is dried exudates from bark of Acacia Senegal and other species of acacia.
 It forms a protective coat around the dispersed particles and acts as protective
colloid.
 It is sticky and not very effective, if used alone. Therefore it is combined with
tragacanth, starch and sucrose in compound tragacanth powder.
 Acacia often has high microbial count. Therefore, preservative id necessary for
suspensions containing acacia.
2. Tragacanth:.
 Is a dried extract from Astragalus gummifer and other species of Astragalus.
 It forms a viscous solution or gel with water.
 It is used both for internal and external products as they are less sticky than acacia.
 It is susceptible to microbial growth and hence preservative is required.

3. Starch:
 Is used in the form of 2.5% mucilage in water with other suspending agents because
of high viscosity of mucilage.
4. Compound tragacanth powder:
 It is a mixture of Powdered acacia, tragacanth, starch and sucrose.
 Used in quantities of 2g per 100 ml of mixture.
5. Sodium alginate:
 It is sodium salt of alginic acid obtained from a seaweed
laminaria.
 It forms a viscous colloidal solution with water, which must not
be heated above 600C as this results in loss in viscosity.
 During preparation of the mucilage, sodium alginate should be
wetted with alcohol to avoid lump formation and mixed with
water using high speed mixer.
 Semisynthetic polysaccharides:

1. Methylcellulose:
 Methylcellulose is soluble in cold water, but insoluble in hot water.
 It is available in different viscosity grades based on its molecular weight. High viscosity
grades such as MC 2500 and 4500 are used as suspending and thickening agents.
 It is susceptible to bacterial growth.
 It is used in both internal and external preparations.
2. Sodium carboxymethyl cellulose:
 It is soluble in both cold and hot water.
 It is available in various viscosity grades, depending upon the degree of
polymerization.* It is susceptible to microbial growth. Therefore, preservatives should
be added.
 3. Microcrystalline cellulose (MCC):
 MCC is prepared form wood cellulose by addition of acid and mechanical action.
 At low concentration it disperses in water forming a colloidal dispersion, while in high
concentration it produces a thixotropic gel.

Inorganic agents:
Clays: These are naturally occurring materials which hydrate readily, absorbing many
times their own volume of water.

a. Bentonite:
• It is very fine cream coloured natural colloidal hydrated aluminium silicate. It hydrates
readily and absorbs large amount of water and swells upto about 12 times its original
volume.
• * Its 2% dispersion is generally used as suspending agent.
b. hectorite:
 It is white powder and it absorbs about 14 times its own volume of water.
 In industry it is used as suspending agent for external use suspension.

c. Veegum:
 It is a creamy white odorless and tasteless powder used as thickening agent in
both internal and external use preparation alone or in combination with other
suspending agents.
 Chemically it is colloidal aluminium magnesium silicate.
d. Aluminum hydroxide :
 It is used as wetting agent for substances not readily miscible with

water.
 It is used as suspending agent for barium sulphate, calamine.
 Synthetic suspending agents:

1. Carbopols (carbomers):
 Is a synthetic copolymer of acrylic acid and allyl sucrose available in several
viscosity grades.
 It is widely used in industry for internal and external preparations.
 It gels in water at concentration of less than 1%.
 It forms acidic, low viscosity solutions in water.
 Carbopol gels are prepared by adding it to water in small amounts with
continuous stirring using a high speed stirrer. The pH is adjusted above 6 using
triethanolamine and stirred slowly taking care not to incorporate air bubbles.
 It is resistant to microbial growth.
2. Colloidal silicone dioxide (Aerosil):

 It is white, non gritty light powder.

 When suspended in a liquid, the particles associate due to hydrogen bonding,
producing a network that obstructs sedimentation.
 A concentration of 1.5-4% in water is enough to stabilize suspensions.
 4. Flocculating agent:

 A controlled flocculation is required to produce suspensions having adequate

redispersibility and high viscosity to minimize sedimentation rate. To achieve this,
flocculating agents are added.
A. Electrolytes
B. Surfactants
C. Hydrophilic polymers
A.Electrolytes:
 These are widely used flocculating agents.
 Formation of flocculated suspensions requires addition of appropriate
concentration of electrolyte.
 Eg: Sodium acetate, sodium citrate.

B. Surfactants:
 Nonionic surfactants form a loose flocculated structure.
C. Hydrophilic polymers:
 Starch, glycerin, cellulose derivatives, tragacanth and carbomer can be used to
control flocculation.
 * Their linear branched chain molecules form a gel like network and get adsorbed
onto the surface of dispersed particles.
 5.Vehicle:

 Suspension is formulated because a drug is insoluble in water.

 Aqueous suspensions utilize water as a vehicle of choice.
 Syrup, or viscosity building agent, or glycerin may be added to enhance the viscosity
of the aqueous phase.
 6. Preservative:

 A suitable preservative should be included in a suspension, to prevent the

growth of microorganism.
 The preservative used should be nontoxic and effective at a low concentration
against a broad spectrum of organisms.
 It should be chemically stable over a wide range of pH and temperature.
 It should be soluble in required concentration.
 It should be odorless, colorless and tasteless.
 It should not get adsorbed/absorbed on the surface of dispersed particles or
should not react with containers and closures.
 Eg: Benzoic acid, cholrbutanol, sodium benzoate.
 7. Coloring and flavoring agents:

 Natural or synthetic coloring agents are added to impart colour to the

preparation, or to improve patient acceptance.
 Flavoring agents are added to improve the patient acceptance.
 Children tend to prefer sweet, fruity flavors.
 8.Sweetening agent:

 Sweetening agent are added to improve palatability of preparation.

 Sucrose, sorbitol and mannitol are often used as sweeteners.
 Saccharine and aspartame are official sweeteners.
 It should be colorless, odorless and tasteless.
 It should be chemically stable at room temperature.
 Synthetic sweeteners such as sodium saccharine can affect the degree of
flocculation.
Stability Problems and Methods to Overcome in Suspensions

Stability is a critical aspect of suspensions, as instability can lead to

problems such as sedimentation, caking, or changes in the effectiveness of
the product. Here’s a detailed look at common stability problems in
suspensions and methods to overcome them:
 1. Sedimentation

Settling in Suspension :
• Settling is a basic phenomenon in suspensions.
• All pharmaceutical suspensions has label on the container as"Shake Well before
Use".
• Based the on type of suspensions, Settling/Sedimentation may differ
• Sedimentation occurs when the solid particles in the suspension settle at the bottom
of the container due to gravity. This can lead to a non-uniform distribution of the
active ingredient.
Characteristics of an Ideal Suspensions related to setteling

1. The solid particles should be of such a size that they do not settle

rapidly.

2. Even if a sediment is formed, it should not form a hard cake at the

bottom of the container.

3. Even if sedimentation occurs, it should be possible to easily redisperse

it on moderate shaking.
Methods to Overcome:
1. Increase Viscosity: Use thickening agents or suspending agents (e.g.,
methylcellulose, xanthan gum) to increase the viscosity of the suspension, which
helps keep particles suspended.
2. Flocculation Control: Use flocculating agents to form loose aggregates that
settle more slowly, reducing sedimentation rate while still allowing for easy re-
dispersion.
3. Particle Size Reduction: Reduce the particle size of the dispersed phase to
decrease the rate of sedimentation. Finer particles settle more slowly than larger
ones.
4. Adjust Formulation: Optimize the concentration of stabilizers and surfactants to
achieve the desired balance between stability and ease of redispersion.
2.Caking

Problem: Caking occurs when particles settle and form a hard, compact layer

at the bottom of the container, making it difficult to re-disperse the suspension.

Methods to Overcome:

i. Flocculation Adjustment: Properly control flocculation to avoid excessive

aggregation that leads to caking. Use flocculating agents to create soft, loose

floccules rather than hard aggregates.

ii. Increase Viscosity: Higher viscosity can help prevent the particles from

settling too quickly and forming a hard cake.

iii. Regular Shaking or Stirring: Design the packaging to allow for easy

shaking or stirring to re-disperse the suspension and prevent caking.

 3. Particle Aggregation

a. Problem: Aggregation occurs when particles clump together, which can lead to
inconsistent dosing and reduced effectiveness.
b. Methods to Overcome:
i. Use of Stabilizers: Employ stabilizers like surfactants or polymers that prevent
particles from coming together and forming aggregates.
ii. Electrostatic Stabilization: Use electrolytes or surfactants to maintain electrostatic
repulsion between particles, keeping them dispersed.
iii. Steric Stabilization: Use polymers or other steric stabilizers that create a physical
barrier around each particle to prevent aggregation.
4. Microbial Contamination

a. Problem: Suspensions can be prone to microbial growth if not properly

preserved, leading to contamination and spoilage.
b. Methods to Overcome:
i. Add Preservatives: Include antimicrobial preservatives (e.g.,
benzalkonium chloride, parabens) to prevent microbial growth.
ii. Use Sterile Techniques: Ensure that the suspension is prepared using
aseptic techniques, especially for injectable formulations, to minimize
contamination risks.
5. pH Changes

a. Problem: Changes in pH can affect the stability of the suspension, potentially

causing particle aggregation or solubility changes.
b. Methods to Overcome:
i. pH Adjustment: Adjust and maintain the pH within an optimal range for the
stability of the suspension using buffer solutions.
ii. Regular Monitoring: Monitor the pH regularly during storage and use,
especially for long-term stability
6. Chemical Degradation
a. Problem: Active ingredients or excipients may degrade over time due to
chemical reactions, affecting the efficacy and safety of the suspension.

b. Methods to Overcome:
i. Use Stabilizers: Incorporate stabilizers and antioxidants that can help
protect the active ingredient from degradation.
ii. Proper Storage: Store the suspension under recommended conditions (e.g.,
temperature, light) to minimize degradation.
7.Temperature Sensitivity

a. Problem: Some suspensions may be sensitive to temperature changes, leading

to changes in viscosity or stability.
b. Methods to Overcome:
i. Temperature Control: Store and transport the suspension within the
recommended temperature range to prevent temperature-induced changes.
ii. Temperature-Stable Formulations: Formulate the suspension with
temperature-stable excipients to maintain stability under varying conditions.
 Stability of suspensions

 A physically stable suspension Should settle slowly and should be

readily redispersed on moderate shaking of the container.
 The particle size of the dispersed substance should remain fairly
constant throughout the shelf life of suspension.
 Should be poured readily and evenly from its container.
The physical stability of suspension depends on the
 Nature of the dispersed phase.
 The dispersion medium or vehicle.
 The additives included in suspension.
 The rate of settling of particles as described by Stoke's law
 Stoke's law and its equation was derived for an ideal situation in which uniform
perfectly spherical particles settle without turbulence.
 Therefore, the stokes equation does not apply precisely to the usual
pharmaceutical suspensions in which the dispersed solid is irregularly shaped.
 Stokes law is given by the equation;
V or dx/dt = d (ps-pp)g/18η
 Where,V or dx/dt = velocity or rate of settling.
 d = diameter of the particles, ps = density of the particle ,
 pp = density of the medium.
 g- acceleration due to gravity
 From the equation it is clear that, The rate of settling is directly
proportional to the diameter of the particle.
 The rate of settling will increase if density of the particles is increased.

Factors affecting stability of suspension:

Based on stokes law there are 3 main factors affecting stability of suspension;
1. Diameter of dispersed particles.
2. Difference between density of dispersed particle and dispersion medium
3. Viscosity of dispersion medium
 1. Diameter of dispersed particles:

 The rate of settling is directly proportional to diameter of dispersed particle.

 Larger the particle, faster would be the rate of settling.
2. Difference between density of dispersed particles and dispersion medium:
 The rate of settling is directly proportional to difference.
 Hence reduction in difference between the density of particle and density of
dispersion medium reduces the rate of settling.

3. Viscosity of dispersion medium:

 The rate of settling is inversely proportional to viscosity of dispersion medium. If
viscosity of the medium is increased, the rate of settling of particles is slower and
a good dispersion is achieved.
Thank
you