Biphasic liquid dosage from

Emulsion Suspension

Emulsion :-
 Biphasic system consisting of two immiscible liquids usually water and oil.
 It consists of two phase
 Internal phase - Dispersed or Discontinues
 External phase - Dispersion or continuous
 Since they are thermodynamic unstable and having homogenous distribution, a suitable
emulsifying agent is required to stabilized the system.
 Size of globules- 0.1 -100μm (Generally).
 The internal phase in monodisperse system (all particles having the same size) should not be
more than 74% of total volume of system.

DIAGRAM

 Example of Emulsion:-
1. Oral Emulsion- Usually O/W type eg:- Caster oil, Cod liver oil
2. Cosmetics- O/W type (Vanishing Cream)
W/O type (Cold Cream)
3. Parenteral Emulsion- Fat soluble vitamins A,D,E and Sex hormones.
4. Diagnostic Emulsion- Radio-opaque emulsion for X-Ray.
 Classification:-

Emulsion

Based on nature of dispersed Based on the globule size Multiple emulsion

phase

O/W (Oil is X/O (Water Microemulsion Fine W/O/W O/W/O

internal is internal (0.01μm)*transparent* Emulsion
phase phase) (0.25-25μm)
*milky*
 Formulation of Emulsion:- Emulsion are formulated by using the following components
 1. Surfactants
2. Antioxidants
3. Preservatives
4. Flavoring agents

1. Surfactants:- (a) Surfactants are used as emulsifying agent/ emulgents.

(b) They decrease interfacial tension.

(c) They prevent coalescence of droplets and stabilize the system by acting as barrier

To droplets.

(d) Mechanism of emulsifying agent.

 Thermodynamically stabilization by decreasing interfacial free energy.

 Formation of rigid interfacial mechanical barrier on the surface of water and oil.
 Formation of electrical double layer.

Surfactants:-

1. Natural – Gum acacia, Agar, Pectin, Starch, Gelatin

2. Semi- synthetic- Methyl cellulose, Sodium Car boxy
3. Synthetic- Anionic, Cationic, Non- ionic
4. Inorganic- Milk of Magnesia, Magnesium Oxide, Bentonite, Carbowax

Types of surfactants

1. Anionic – Ex:- Sodium lauryl sulphate (SLS), Triaton-X200, Sodium acetyl sulphate
2. Cationic- EX:- Benzalkonium chloride, Cetyl trimethyl ammonium
3. Non- ionic-Tween, Span, Myrj, Brij, Diethanolamine, PEG.
4. Amphoteric- N- alkylamino acid, Lecithin.
 From o/x emulsion- Tweens,Acacia, Bentonite
 From w/o emulsion- Spans, (Trick SLB→ Lipophillic)
 Hydrophilic Lipophilic Balance (HLB) Scale
 Determined by Griffin
HLB Scale Category
1-3 Antifoaming agents
4-8 W/O Emulsifying agents
7-9 Wetting agents
9-16 O/W emulsifying agents
 13-15 Detergents
16-18 Solubilizing agent
 Bencraft rule describe the relation ship between the nature of emulsifying agent and type
of emulsion formed.
 If surfactant is more soluble in water- o/w emulsion formed
 If surfactant is more soluble in oil- w/o emulsion formed

2. Antioxidants- Propyl gallate, Ascorbic acid, Tocopherol etc are used to prevent from oxidation.

3. Preservatives- Prevent the growth of microorganism.

4. Flavoring agent

 Preparation method
 Dry gum method
 Wet gum method
 Industrial method( Large scale preparation)
 Mechanical stirrer
 Turbine type mixture
 Paddle blade, Counter rotating blade, Planetary action blde.
 Homogenizer
 Achieved by forcing the mixture through a small orifice at high pressure.
 Pressure 500-25000 psi.
 Ultra- sonifiers
 Use ultrasonic energy
 Piezoelectric device, Pressure 150-300 psi
 Based on principle Pohlman liquid whistle
 Colloidal Mills
 Operates on the principle of high shear
 Preparation of relatively viscous emulsion
 Identification test
1. Dye solubility test- Based on the principle that emulsion is always miscible with external
phase
 Water soluble dye- Amaranth, Methylene blue
 Oil soluble dye- Sudan III, Scarlet red
2. Dilution test- Based on the principle that emulsion is always miscible with external phase
3. Conductivity test- Current pass it is o/w and if it does not pass it w/o.
  Direction of creaming test- If creaming is at the upper side, it is o/w and if it is downward, it is
w/o type of emulsion.
 Fluorescent test
 CoCl2/ filler paper test
 Instability of Emulsion
1. Coalescene
 Coalescence is the growth process in which small particles merge with each other to
from larger particle.
 Coalescence is followed by creaming stage.
 Mainly occurs due to insufficient emulsifying agent.
2. Flocculation
 In these globules comes closer to each other and from flocs in the external phase
 Leads to instability
 Extent of flocculation of globules depends on
a) Globule size distribution – Uniform- Prevent flocculation
b) Changes on globular surface- achieved by ionic emulsifying- changes exert
Repulsive force
c) Viscosity of the external medium- Globule be immobile and prevent
Flocculation.

Coalescence Flocculation

Good Emulsion

Creaming iv. Breaking

3. Creaming
 It is the concentration of globules at the top or bottom of emulsion.
 Two type Upward (O/W)
Downward(W/O)
 Prevented by
a. Reducing particle size by homogenization
b. Increasing viscosity by adding thickening agent
c. Reducing the difference in densities
4. Breaking or Cracking
 Complete separation of oil and aqueous phase, irreversible
 Occurs due to addition of incompatible emulsifying agent e.g-
 Monovalent +Divalent soap
 5. Phase inversion
 In phase inversion, o/w type emulsion changes into w/o type and vice versa
 Brought about by changing the phase volume ratio, temperature change or by
addition electrolyte.
 Factors which improves physical stability
1. Particle size
 When size of dispersed globule is less- decrease creaming
 According to stokes’ law – when diameter of globule is reduced to half, creaming
rate reduced to four fold.
2. Particle size distribution
3. Viscosity
4. Phase volume ratio- Upper limit is 74% (Internal phase)
5. Temperature changes- Low temperature break emulsion

Phase volume ration Type of flow

5% Newtonian
50% Pseudoplastic
74% Plastic flow
 Points to remember
 Micelles are the result of self structuring of surface active material in order to reach a state of
minimum energy.
 Concentration at which micelle formation start is known as CMC(Critical micelle concentration)
 Internal and external phase of emulsion have recently been identified by freeze fracture
Micrography.
 Antifoaming agent- Ethyl alcohol, Silicon derivative oil.
SUSPENSION
 Two phase system consisting of a finely divided solid dispersed in a liquid vehicle.
 Thermodynamic stable, heterogeneous system.
 Size of the particle- 0.5-5 μm
 Suspension consists of two phase Internal (Dispersed phase) eg:- Liquid
External (Continuous phase) eg:- Particulate matter

 Formulation main concerned is to decrease the rate of settling and permit easy resuspendibility.
Advantages
1. Stability
 Some drugs are unstable in solution form.
  E.g. Penicillin G-Soluble but unstable so procaine penicillin G is take as
suspension.
2. Mask the taste
 Chloramphenicaol- Bitter taste- Cholramphenicon almitate is used as suspension
 Quinnine- Bitter taste- Quinine tannate is used as suspension.
3. Prolonged action
 Protamine Zinc-Insulin suspension
 Procaine penicillin G suspension
4. Bioavailability
 Solution > Suspension> solid dosage form
 Due to large surface area and high dissolution rate
 Dilute Suspension- May have 2-10w/v solid.
 Concentrated Suspension-May have 50% w/v solid.
 Types of Suspension:-
Flocculated Suspension Deflocculated suspension
Particles from loose aggregate and from Particle exists as separate entities
network like structure
Rate of sedimentation is high Rate of sedimentation is low
Sediment is easy to redisperse Sediment is difficult to redisperse
Sediment is loosely packed and does not from a Sediment is very closely packed and for a hard
hard cake so preferred than deflocculated cake

 Formulation of suspension
1. Flocculating agents
 They leads to decrease in repulsion potential and make particle come together to from
loosely arranged floccules.
 Act by reducing the surface tension. E.g. SLS, Tweens, Span, Carbowax.
2. Suspending agent, Thickning agent- Added to the dispersion medium to lend its structure
to assist in the suspension of the dispersed phase.
a. Polysaccharide=> Natural- Acacia, Starch, Talc
Synthetic- MC, HPMC
b. Inorganic agents=> Clay, AI(OH)3
c. Synthetic => Carbomer, Collodial SiO2
3. Protective Colloids – They are absorbed on insoluble particle and increase the strength of the
hydration layer formed around suspended particles through hydrogen bonding and molecular
interaction. E.g- Gelatin, natural gum and cellulosic derivatives.
4. Wetting agent
  Decrease interfacial tension between solid particle and liquid medium.
 E.g. Alcohol in tragacanth mucilage, Glycerin in sodium alginate.
5. Preservative
 Benzoic acid, Methyl paraben, Benzoic acid, Sodium benzoate.
6. Organoleptic additive

 Coloring agent, sweetening agent, Flavoring agents.

 Stability of suspension
 Can be easily redisperse homogeniously with moderate shaking.
 Easily poured throughout the life.
 Stable pharmaceutical suspension- Flocculated
a) Wetting
 Form a film over solid when high affinity between liquid and solid.
 Wetting angle
0 = 00 → Completely wet
0 = 900 → Partially wet
0 = 1800 → Not wet
 Various test for wetting ability- Through, Gauge, Drave test, Emperic test.
b) Particle – Particle interaction
 Flocculated system- Separated by about 1000 to 2000 A0 hence particle are loosely
structured.
 Deflocculated system- When energy barrier is crossed particle comes closer, this forms
cake.
c) Electro kinetic method
 Determination of surface electric charge or Zeta potential of suspension is helpful to find
out the stability of suspension.
 Certain zeta potential- produce more stable suspension.
d) Sedimentation method
 Most important parameter in evaluation stability of suspension.
 Determined by sedimentation volume= Ultimate volume of sediment
Initial volume of sediment
 Sedimentation volume= 1- No sedimentation
 Sedimentation volume= 0- Complete sedimentation takes place.
 Rate of sedimentation expressed by Stoke’ s law
𝒅𝒄
 =D2 (d1-d2) g
𝒅𝒕
 18n
dc/dt= Rate of sedimentation
n= Viscosity of the suspension
d1d2 = Density difference between 2 phases
D= Diameter of particle
 Condition of Stoke’ s law
 Particle should be spherical- In suspension irregular
 Particle should settle freely & independently
Dilute 0.5 to 2% solid Stokes law apply
Concentration 5 to 10% solid Hindrance occurs
 Stokes law applicable to deflocculated system. Where particle settle independently.
 Points for remember
 Swamping
a) Increase in concentration of ions in the solution decrease the thickness of
double layer and therefore aggregation occur.
 Subsidence
a) Describe the settling of an aggregated system.
 Ostwald ripening
a) Cyclization change in temperature in suspension
b) Ostwald ripening
 Freeze thaw cycling
a) Technique is particularly applicable to stressing suspension for stability
testing purpose.
 Micro electrophoresis apparatus
a) Instrument permitted to measurement of migration velocity of the
particle.
 Consistency of suspension evaluated by
a) Cup & Bob viscometer
b) Cone & plate viscometer
 Settling behavior of suspension
a) Evaluated by Brookfield viscometer with T- spindle
 Levigation- Particle size reduction by grinding
 Pulverisation- Process of powdering.