Biphasic Liquid Dosage Forms

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Ahmad Salawi, Ph.D.

Pharmaceutics Department
College of Pharmacy
Jazan University
asalawi@jazanu.edu.sa
LEARNING OBJECTIVES

 Definition, classification, advantages and disadvantages of emulsions

and suspensions
 Flocculated and deflocculated suspensions
 Suspending agents, preparation and stability of suspensions
 Emulsifying agents, preparation and stability of emulsions
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SUSPENSIONS

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• A Pharmaceutical suspension is a coarse dispersion in which the
insoluble solid is dispersed uniformly throughout the external phase.
• The average size of the suspended particles ranges from 0.5 µm
to 5 µm.
• The external phase (suspending medium) is generally aqueous.
• In some cases it may be an organic or oily liquid for non oral use;
or a gas in inhalation or aerosol.
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CLASSIFICATION OF SUSPENSIONS
1. Based on General Classification:
 Oral suspension e.g. antacid, antibiotic
 Externally applied suspension e.g. lotion
 Parenteral suspension e.g. zinc-insulin suspension
 Ophthalmic suspension e.g. chloramphenicol suspension
2. Based on Proportion of Solid Particles:
 Dilute suspension (2 to10% w/v solid)
 Concentrated suspension (50% w/v solid and above)
3. Based on Electrokinetic nature of Solid Particles:
 Flocculated suspension
 Deflocculated suspension
ADVANTAGES
 Suspensions are used for insoluble or poorly soluble drugs which
required to be given orally in liquid dosage forms. ( In case of
children, elderly, and patients have difficulty in swallowing solids
dosage forms)
 To overcome the instability of certain drug in aqueous solution:
 Reduce the contact time between solid drug particles and dispersion
media increase the stability of drug like Ampicillin by making it as
reconstituted powder.
 A drug that degraded in the presence of water, can be suspended
in non-aqueous vehicles. Example: phenoxymethyIpenicillin
ADVANTAGES

 Exhibits higher rate of bioavailability than several dosage forms.

Bioavailability is in following order:

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

 Mask the unpleasant/bitter taste of drug. E.g. Chloramphenicol as

a suspension dosage form.
 In aerosol suspension the drug is suspended in mixture of
propellants.(gas)
DISADVANTAGES

• It is bulky, sufficient care must be taken during handling and

transport.
• Uniform and accurate dose can not be achieved unless suspension
are packed in unit dosage form.
FLOCCULATED VS DEFLOCCULATED SUSPENSIONS
 Flocculated Suspensions:
• Floccules (loose aggregates) are formed.
• Flocculated suspensions sediment more rapidly
but easily redispersed by agitation.

 Deflocculated suspensions:
• Individual particles are settling.
• Rate of sedimentation is slow.
• This phenomenon called ‘caking’ or ‘claying’.
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METHOD OF PREPARATION:
• The preparation of suspension includes three methods:

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A.
B.
C.
Use of controlled flocculation
Use of structured vehicle
Combination of both.

A. Controlled flocculation:
Controlled flocculation of particles is obtained by adding flocculating
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agents, such as:

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(1)Electrolytes (2)Surfactants (3)Polymers
B. Structured vehicle:
Structured vehicles called also thickening or suspending agents.
They are aqueous solutions of natural and synthetic gums.
These are used to increase the viscosity of the suspension.
It is applicable only to deflocculated suspensions.
E.g. Methyl cellulose, sodium carboxymethyl cellulose, acacia, gelatin
and tragacanth.

C. Flocculation in structured vehicles:

Sometimes suspending agents can be added to flocculated suspension
to retard sedimentation
Examples of these agents are:
Carboxymethylcellulose (CMC), Carbopol 934, Veegum, and bentonite
THE GENERAL GUIDELINES TO SUSPENSION FORMULATION:
Particles
Be
Addition of wetting agent and dispersion medium

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Uniform dispersion of deflocculated particles
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A B C

Incorporation of Addition of Addition of

structured vehicle flocculating agent flocculating agent

Flocculated suspension
Flocculated suspension
as final product
Incorporation of
structured vehicle
Deflocculated suspension
in structured vehicle
Flocculated suspension
as final product
in structured vehicle as
final product
STABILITY OF SUSPENSION

• Suspension stability are associated with:

 Sedimentation of the suspended particles
 Changes in the particle size and shape etc.

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 Changes in the rheology

 Changes in the electrokinetic properties of the suspension
(zeta potential).
 EMULSION of
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• An emulsion is a heterogeneous system which is thermodynamically
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unstable consisting of two immiscible liquids in which one phase is

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dispersed as fine globules in to the other liquid phase by using the third
substance as an emulsifying agent.
 EMULSION

• A. Two immiscible liquids.

• B. An emulsion of Phase II dispersed in Phase I. ɧ%
• C. The unstable emulsion progressively separates.9¥
• D. The surfactant (purple outline around globules)
• positions itself on the interfaces between Phase II and Phase I,
stabilizing the emulsion

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PHARMACEUTICAL EMULSIONS

As
1. Lotions and Liniments
2. Emulsions for ophthalmic use
3. Parenteral emulsion: (IV) administration
4. Ointments and creams
5. Vitamin drops
TYPES OF EMULSIONS
• Based on dispersed phase:
 Oil in Water (O/W): Oil droplets dispersed in water
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 Water in Oil (W/O): Water droplets dispersed in oil

 HAKEEM → 20-200

TYPES OF EMULSIONS nm

micro → as a 01 →
Erin

Mulero → Im
to 50
• Based on size of liquid droplets:
 Macroemulsion
 Microemulsion
 Nanoemulsion
 Macroemulsions 0.2 – 50 mm (Kinetically stable)
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 Microemulsions are thermodynamically stable optically

transparent isotropic mixtures of a biphasic o/w systems stabilized
with surfactants. The diameter of the droplet may be 0.01 – 0.2 mm
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 Nano-emulsion droplet size around 20 – 200 nm

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EMULSION IDENTIFICATION TESTS
• Tests for Emulsion Type (W/O or O/W emulsions):
1. Dilution Test:
 o/w emulsion can be diluted with water.
 w/o emulsion can be diluted with oil.
2. Conductivity Test:
 If electric current conducted, then it is o/w
 If non conducted, then ☐w/o.
.
EMULSION IDENTIFICATION TESTS
3. Dye-Solubility Test:
 water soluble dye will dissolve in the aqueous phase and when it
is added, it gives continuous color in o/w emulsion.
 oil soluble dye will dissolve in the oil phase, if oil soluble dye
added in0 o/w emulsion, a discontinuous color observed.
If
4. Fluorescence Test:
 Many oils exhibit fluorescence when exposed to UV light. When a
w/o emulsion is exposed to fluorescent light under a microscope,
the entire field fluoresces. If fluorescence is spotty, the emulsion is
.

o/w type.
- KETT
METHODS OF PREPARATION
1. Dry Gum Method

¥:2. Wet Gum Method

3. Bottle Method: for volatile oils & not suitable for viscous oils

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Primary emulsion & secondary emulsion
Formula of primary emulsion:
 "4:2:1" Method
 4 parts (volumes) of fixed oil
 2 parts of water
 1 part of gum
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CONTINENTAL OR DRY GUM METHOD j >

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ENGLISH OR WET GUM METHOD
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 INSTABILITY OF EMULSION
There are three types of instability :
flocculation, coalescence and creaming.
Flocculation describes the process by which the

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Coalescence is another form of instability, which
describes when small droplets combine to form
progressively larger ones.
Creaming is the migration of one of the substances to
the top (or the bottom, depending on the relative
densities of the two phases) of the emulsion.
density
 EMULSION BREAKING
• Separation of the internal phase from the
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§ ; g. ! emulsion. This is irreversible.
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• Factors that influence the rate of creaming and

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Breakin sedimentation:
- Globule size
- Viscosity density
viscosity
- Density
Globule
- Temperature.
 STRATEGIES TO REDUCE
CREAMING

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S.No Principle Method
←
1 Reduce droplet size Homogenizer

2 Reduce density Add oils that have density

difference Greater than the density of water
3 Increase viscosity of Add thickening agents or gelling
continuous phase agents Methylcellulose
 CLINICAL USES OF EMULSIONS
Parenteral Emulsions
Total Parenteral Nutrition(TPN) - IV Lipid Emulsions.
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Emulsification of highly lipophillic drug (Taxol) anticancer agent

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formulated as an emulsion.
Oral Emulsions
Liquid oral preparation containing distasteful oils, eg. Vitamins A, D,
and E when formulated as an emulsion have better patient
acceptance.
Topical Emulsion
O/W emulsions: Oil soluble drugs are dispersed in oil and
emulsified with aqueous phase.
Micro emulsions are used for ophthalmic (eye)as well as for trans
,
dermal drug delivery
 (TOTAL PARENTERAL NUTRITION)
(INTRAVENOUS LIPID EMULSIONS)
Definition:
“Sterile, isotonic emulsion preparations intended for
intravenous administration containing all nutritional
requirements”
Intravenous lipid emulsion contains:
1.Macronutrients
 CHO, Proteins, Lipids
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2.Micronutrients
 Electrolytes, Trace element, Vitamins
3.Water
(TOTAL PARENTERAL NUTRITION) TPN

Composition of (Intravenous fat emulsions):

Soya oil
Amino acids
Glucose
Electrolytes
Vitamins (ADEK , B.complex and C )
Lecithin
Water