MICROENCAPSULATION

Microencapsulation is a process by which very tiny droplets or particles

of liquid or solid material are surrounded or coated with a continuous
film of polymeric material.

The uniqueness of microencapsulation is the smallness of the coated

particles and their subsequent use and adaptation to a wide variety of
dosage forms
 REASONS FOR
MICROENCAPSULATION
1. The primary reason for microencapsulation is found to be either
for sustained or prolonged drug release.
2. This technique has been widely used for masking taste and odor
of many drugs to improve patient compliance.
3. This technique can be used for converting liquid drugs in a free
flowing powder.
4. The drugs, which are sensitive to oxygen, moisture or light, can
be stabilized by microencapsulation.
5. Incompatibility among the drugs can be prevented by
microencapsulation.
 REASONS FOR
MICROENCAPSULATION
6. Vaporization of many volatile drugs e.g. methyl salicylate and
peppermint oil can be prevented by microencapsulation.
7. Many drugs have been microencapsulated to reduce toxicity and
GI irritation including ferrous sulphate and KCl.
8. Alteration in the site of absorption can also be achieved by
microencapsulation.
9. Toxic chemicals such as insecticides may be microencapsulated to
reduce the possibility of sensitization.
10. Microencapsulated vitamin A palmitate has shown enhanced
stability.
Advantages of Microencapsulation
• Reliable means to deliver the drug to the target site with specificity, if
modified, and to maintain the desired concentration at the site of interest
without untoward effects

• Solid biodegradable microspheres have the potential throughout the particle

matrix for the controlled release of drug

• Microspheres received much attention not only for prolonged release, but
also for targeting of anticancer drugs to the tumour

• The size, surface charge and surface hydrophilicity of microspheres have

been found to be important in determining the fate of particles in vivo

• Studies on the macrophage uptake of microspheres have demonstrated their

potential in targeting drugs to where pathogens reside
Disadvantages of Microencapsulation
 Core Material
 The core material is defined as the specific material to be coated,
that can be liquid or solid in nature

 The composition of the core material can be varied as the liquid

core can include dispersed and/or dissolved material

 The solid core can be mixture of active constituents, stabilizers,

diluents, excipients and release-rate retardants or accelerators

 The ability to vary the core materials composition provides

definite flexibility and utilization of this characteristic often allows
effectual design and development of the desired microcapsules
properties
 Properties of Some Microencapsulated Core
Materials
Core Material Characteristic Purpose of Encapsulation Final Product
Property Form

Acetaminophen Slightly water-soluble Taste-masking Tablet

solid

Aspirin Slightly water soluble Taste-masking; sustained Tablet or

release; reduced gastric capsule
irritation

Islet of Langerhans Viable cells Sustained normalization of Injectable

diabetic condition

Vitamin A Nonvolatile liquid Stabilization to oxidation Dry powder

palmitate

Menthol/ methyl Volatile solution Reduction of volatility; Lotion

salicylate camphor sustained release
 Coating Material
• The selection of appropriate coating material decides the physical and
chemical properties of the resultant microcapsules/microspheres

• Factors for consideration while selecting a polymer

– Stabilization
– Reduced volatility
– Release characteristics
– Environmental conditions

• The polymer should be capable of forming a film that is cohesive with

the core material

• It should be chemically compatible, non-reactive with the core material

and provide the desired coating properties such as strength, flexibility,
impermeability, optical properties and stability
 Coating Material

• Generally hydrophilic polymers, hydrophobic polymers (or) a

combination of both are used for the microencapsulation process

• Examples of coating materials include gelatin, polyvinyl alcohol, ethyl

cellulose, cellulose acetate phthalate and more

• The film thickness can be varied considerably depending on the

surface area of the material to be coated and other physical
characteristics of the system
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Coacervation and phase Spray–drying and congealing

separation Fluid bed coating
In-situ polymerization Pan coating
Sol-gel encapsulation Solvent evaporation
Matrix polymerization Wurster process/Air-suspension
Super critical CO2 assisted coating
Polycondensation microencapsulation Centrifugal extrusion
Vibrational Nozzle
 Representative Coating Materials and
Applicable (ME) Process
Coating Multiorifice- Phase Pan Spray Air Solvent
Materials Centrifugal Separation- Coating Drying and Suspension Evaporation
Coacervation Congealing

Gelatin X X X X X X

Gum X X X X X
Arabic

Ethyl X X X X X
cellulose

Paraffin X X X X X

Shellac X X X X

CAP X X X X X
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Coacervation and phase Spray–drying and congealing

separation Fluid bed coating
In-situ polymerization
Sol-gel encapsulation Pan coating
Matrix polymerization Solvent evaporation
Super critical CO2 assisted
Wurster process/Air-suspension
Polycondensation microencapsulation coating
Centrifugal extrusion
Vibrational Nozzle
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Coacervation and phase Spray–drying and congealing

separation Fluid bed coating
In-situ polymerization Pan coating
Sol-gel encapsulation Solvent evaporation
Matrix polymerization
Super critical CO2 assisted
Wurster process/Air-
Polycondensation microencapsulation suspension coating
Centrifugal extrusion
Vibrational Nozzle
 Air Suspension /Fluidized bed
coating(Wurster process)
• The Wurster process is a coating technique that is
well suited to uniformly coat or encapsulate
individual particulate materials

• This technology is characterized by the location of a

spray nozzle at the bottom of a fluidized bed of solid
particles

• The particles are suspended in the fluidizing air (0.4-

0.6 bar) stream that is designed to induce a cyclic
flow of the particles past the spray nozzle

• The nozzle sprays an atomized flow(0.2-0.4 bar) of

coating solution, suspension, or other coating vehicle
 
• The atomized coating material collides with the
particles as they are carried away from the nozzle
 Wurster process
• The temperature of the fluidizing air (depends on the product i.e.
temperature it can withstand) is set to appropriately evaporate solution or
suspension solvent or solidify the coating material shortly after colliding
with the particles

• All coating solids are left on the particles as a part of the developing film or
coating

• This process is continued until each particle is coated uniformly to the

desired film thickness

• The cyclic process is repeated several hundred times depending upon:

– Purpose of microencapsulation
– Coating thickness required
– Effective coating ensuring encapsulation
• The Wurster process is an industry recognized coating technique for
precision application of film coat to particulate materials such as
powders, crystals, or granules

• The technology can be used to encapsulate solid materials with

diameters ranging from near 50µm to several centimeters  

• The process has a greater drying capacity than other coating systems due
to a relatively high fluidizing air velocity

• Since the particles actually separate as they are carried away from the
nozzle, it is possible to coat small particles without agglomeration

• Coating possibilities are relatively unlimited including the ability to

place a hydrophilic coat on a hydrophobic core, or a water-based
coat on a water-soluble core 

• Coating properties can be optimized with coat formulation parameters,

processing conditions, and layering
 Processing variables
• Density, surface area, melting point, solubility, friability,
volatility, crystallinity, and flowability of the core material
• Coating material concentration (or melting point if not a
solution)
• Coating material application rate
• Volume of air required to support and fluidize the core
material
• Amount of coating material required
• Inlet and outlet operating temperatures
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Coacervation and phase Spray–drying and congealing

separation Fluid bed coating
In-situ polymerization Pan coating
Sol-gel encapsulation
Solvent evaporation
Matrix polymerization
Super critical CO2 assisted Wurster process/Air-suspension
coating
Polycondensation microencapsulation
Centrifugal extrusion
Vibrational Nozzle
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Coacervation and phase

separation
Spray–drying and
In-situ polymerization
congealing
Sol-gel encapsulation Fluid bed coating
Matrix polymerization Pan coating
Super critical CO2 assisted Solvent evaporation
Polycondensation microencapsulation Wurster process/Air-suspension
coating
Centrifugal extrusion
Vibrational Nozzle
 Spray drying
• Spray Drying is a unique method to convert a solution, suspension or
emulsion into a solid powder in one single process step.
• The feed is atomized into a spray and the contact between the spray
and drying medium takes place resulting in moisture evaporation.
This is continued till dry product is obtained
• Construction and working
Spray drying is a sequence of four processes:
1. Atomization of feed into a spray
2. Contact of spray and air
3. Evaporation from droplet (removal of moisture)
4. Separation of dried product from air
 Spray Drying
• Microparticles are created by spraying complex liquid mixtures
containing an active principle that is dissolved/ dispersed in an
organic or aqueous polymer solution

• The production of microspheres /micro capsule by this method

depends on whether the initial formulation was in the form of a
solution, suspension, or emulsion

• Commercially used biodegradable polymers are PLA, PLGA, PCL,

Eudragit®,gelatin, polysaccharides or related biopolymers

• First commercialized injectable microspheres of bromocryptine

(Parlodel®; Sandoz, Switzerland)
 Spray Drying
• Parameters affecting the process, flow rate, nozzle
geometry and solution viscosity

Advantages:
One-step quick process and is continuous
Easy to scale-up
Inexpensive
 Spray Drying
Disadvantages:
• Significant loss of the product due to adhesion of the
microparticles to the inner wall of the spray-drier
apparatus, or to agglomeration of the microparticles

• Formation of fibers instead of microspheres could occur

when the sprayed solution is not sufficiently broken up
 Spray Congealing
• The action in spray drying is primarily that of evaporation,
whereas in spray congealing it is that of a phase change from a
liquid to a solid.
• The two processes are similar, except for energy flow.
• In the case of spray drying, energy is applied to the droplet,
forcing evaporation of the medium resulting in both energy and
mass transfer through the droplet.
• In spray congealing, energy only is removed from the droplet,
forcing the melt to solidify.
• Spray congealing can be done by spray drying equipment where
protective coating will be applied as a melt.
 Spray Congealing
• Core material is dispersed in a coating material melt rather than a coating
solution.
• Coating solidification is accomplished by spraying the hot mixture into cool air
stream.
• Waxes, fatty acids, and alcohols, polymers which are solids at room temperature
but meltable at reasonable temperature are applicable to spray congealing.
• Albertini B et al., prepared mucoadhesive micro particles and designed an
innovative vaginal delivery systems for econazole nitrate (ECN) to enhance the
drug antifungal activity.
• Seven different formulations were prepared by spray-congealing, a lipid-
hydrophilic matrix (Gelucire((R)) 53/10) was used as carrier and several
mucoadhesive polymers such as chitosan, sodium carboxymethylcellulose and
poloxamers (Lutrol((R)) F68 and F127) were added
 Techniques for manufacturing
microcapsules
Chemical process Physico-Chemical process Physico-Mechanical process

Interfacial polymerization Spray–drying and congealing

Coacervation and
Fluid bed coating
In-situ polymerization
phase separation Pan coating
Solvent evaporation
Matrix polymerization Sol-gel encapsulation Wurster process/Air-suspension
coating
Polycondensation Super critical CO2 assisted Centrifugal extrusion
microencapsulation Vibrational Nozzle
 Coacervation Phase Separation
Coacervation Phase Separation
• The process consists of three steps:
 Coacervation Phase Separation
• Step I Formation of three immiscible chemical phases –

 A liquid manufacturing vehicle phase- the solvent for the polymer,

 a core material phase
 a coating material phase
• To form the three phases, the core material is dispersed in a solution of the
coating polymer, the solvent for the polymer being the liquid manufacturing
vehicle phase
• The coating material phase, an immiscible polymer in a liquid state, is formed by
utilizing one of the methods of the phase separation-coacervation, i.e.,by
• changing the temperature of the polymer solution;
• by adding a salt, nonsolvent, or incompatible polymer to the polymer solution;
• by inducing a polymer - polymer interaction
 Coacervation Phase Separation
Step II – Deposition of liquid polymer coating
– This process consists of depositing the liquid polymer coating upon the core
material

– This is accomplished by controlled, physical mixing of the material in the

manufacturing vehicle

– Deposition of the liquid polymer coating around the core material occurs if
the polymer is adsorbed at the interface formed between the core material
and the liquid vehicle phase, and this adsorption phenomenon is a
prerequisite to effective coating

– The continued deposition of the coating material is promoted by a reduction

in the total free interfacial energy of the system
Coacervation Phase Separation
Step III Rigidization of the coating

– It involves rigidizing the coating, usually by thermal, cross-

linking, or desolvation techniques, to form a self-sustaining
microcapsules

– Equipment required for microencapsulation by this method

is relatively simple; it consists mainly of jacketed tanks with
variable speed agitators
 Coacervation Phase Separation

Schematic representation of the coacervation process. (a) Core material dispersion in

solution of shell polymer; (b) separation of coacervate from solution; (c) coating of
core material by microdroplets of coacervate; (d) coalescence of coacervate to form
continuous shell around core particles.
 Temperature Change- CPS
• A general temperature-composition
A
phase diagram for a binary system
comprised of a polymer and a solvent E
• A system having an over all composition,

Temperature
represents as point X on the abcissa
exists as a single-phase, homogenous
solution at all points above the phase-
boundary or binodal curve, FEG C D
• As the temperature is decreased from B
point A along the arrowed line AEB, the F G
phase boundary is crossed at point E, 0 X 100
and the two-phase region is entered

• Phase separation of the dissolved polymer occurs in the form of immiscible

liquid droplets, and if a core material is present in the system, under proper
polymer concentration, temperature, and agitation conditions the liquid
polymer coalesce around the dispersed core material particles, thus forming the
embryonic microcapsules
 Temperature Change- CPS
• The phase boundary curve indicates that A
with decreasing temperature, one phase E
becomes polymer-poor(vehicle phase) and

Temperature
the second phase(coating material phase)
becomes polymer rich
• At point B, for instance the segmented tie
line suggests that vehicle phase is pure D
C
solvent at point C B
• Whereas the coexisting phase, point D is a F G
concentrated polymer solvent mixture 0 X 100
• In practice, the loss of solvent by polymer
rich phase can constitute gelation of polymer
and hence rigidization of the microcapsule
polymer coating.
 EXAMPLE
• Ethyl cellulose, a water insoluble polymer, is applied to a water soluble
core material, N-acetyl p-aminophenol, by utilizing the temperature-
solubility of the polymer in solvent cyclohexane.
• Ethyl cellulose is insoluble in cyclohexane at room temperature, but is
soluble at elevated temperatures
• Therefore a 2 % ethyl cellulose dispersion is first prepared in cyclohexane.
This is then heated to form one phase system
• A finely divided core material is dispersed in the above solution with
stirring
• Allowing the mixture to cool with continuous stirring effects phase
separation coacervation of ethyl cellulose and microencapsulation of core
material
• Allowing the mixture to cool further to room temperature accomplishes
gelation and solidification of coating
• the microcapsules can be collected by filtration, decantation or
centrifugation techniques
 Incompatible Polymer Addition
• Liquid phase separation of a polymeric coating
material and subsequent microencapsulation is
achieved by utilizing the incompatibility of Solvent 100%
dissimilar polymers existing in a common solvent
A
• A ternary system consisting of a solvent and two
polymers X and Y E
• If an immiscible core material is dispersed in a D
solution of polymer Y (point A) C B
• And polymer X is added to the system denoted by
the arrowed line, the phase boundary will be
crossed at point E
• As the two-phase region is penetrated with the
further addition of polymer X, liquid polymer 100%
100%
immiscible droplets form and coalesce to form Polymer X
Polymer Y
embryonic microcapsules
 Incompatible Polymer Addition
• The polymer that is strongly adsorbed at
the core material-solvent interface, Solvent 100%
polymer Y, becomes the coating material
E A
• In practice, solidification of the coating
material is accomplished by further
penetration onto the two-phase region, C D
B
chemical-cross linking or washing the
embryonic microcapsules with a liquid that
is a nonsolvent for coating , polymer Y
and is a solvent for polymer X.
100%
100%
Polymer X
Polymer Y
 Incompatible Polymer Addition
• Eg. Microencapsulation of Methylene Blue with
Ethyl Cellulose.
• EC is dissolved in toluene to yield polymer conc. Solvent 100%
of 2% by weight.
E A
• MB , insoluble in toluene is dispersed with stirring
in the polymer solution in ratio of 4:1.
• PSC is achieved by slowly adding liquid D
C B
polybutadiene in sufficient quantity to yield a
ration of 25:1.
• The PB being quiet soluble in toluene and
incompatible with EC, effects the demixing of EC
from PB-toluene solution and subsequent
microencapsulation of the dispersed MB results. 100%
100%
•
Polymer X
The EC coating is solidified by adding a Polymer Y
nonsolvent for EC such as hexane.
• Also PB being soluble in hexane is washed from
the mixture by decantation.
• The product is collected by std filtration and drying
techniques.
 Non Solvent Addition
• A liquid that is non solvent for a given
polymer is added to the solution of polymer
Solvent 100%
to induce phase separation
A
• The resulting immiscible liquid polymer can E

be utilized to effect microencapsulation of an

immiscible core material D

• A 5%,w/v methyl ethyl ketone solution of B

cellulose acetate butyrate (CAB) is C

prepared, and in it , micronized
methylscopolamine hydrobromide is
dispersed with stirring 100% 100% POLYMER
• A core to coat material ratio of 2:1 is used NONSOLVENT

The resulting mixture is heated to 55°C and isopropyl ether, a non solvent for
the polymer is added slowly to effect phase separation and microencapsulation of
suspended core material. The system is cooled to room temperature and
microcapsules separated by centrifugation
 Salt Addition
• Soluble inorganic salts can be added to
aqueous solutions of certain water-soluble WATER100%
polymers to cause phase separation. A
• Eg. An oil soluble vitamin E

microencapsulation can be induced by

adding sodium sulfate to a gelatin solution D
B
• An oil soluble vitamin is dissolved in corn
oil and is emulsified to the desired drop size C

in 10% solution of high quality pigskin

gelatin.
100% SALT
• 20 parts of oil to 100 parts of water by 100% POLYMER

weight, are used for the preparation of O/W

emulsion.
• The emulsification process is conducted at
50oC, well above the gelation temperature of
gelatin.
 Salt Addition
• With the temp. of emulsion maintained at
50oC, phase separation/coacervation is WATER100%
induced by slowly adding a 20% solution of A
sodium sulfate. E

• The salt solution is added in the ratio of 10

parts emulsion to 4 parts salt solution D
B
• The addition of salt solution to the
continuously stirred emulsion effects the C

microencapsulation of oil droplets with a

uniform coating of gelatin.
100% SALT
• The resultant gelatin coating is rigidized by 100% POLYMER

transferring the mixture into a sodium sulfate

solution that is 7% by wt and is maintained at
19oC with continuous agitation.
 Salt Addition
• The microencapsulated product is collected
by filtration, washed with water, chilled WATER100%
below the gelation temp. of the gelatin (to A
remove salt) and voided by water with E

standard drying techniques.

D
B

100% SALT 100% POLYMER

 Polymer-Polymer Interaction
• The interaction of oppositely charged
polyelectrolytes can result in the formation WATER100%
A
of a complex having such reduced solubility
that phase separation occurs.
C
• The phase diagram for a ternary system B
comprises of two dissimilarly charged D

polyelectrolytes and the solvent, water.

• In dilute solution region, interaction of the
oppositely charged polyelectrolytes occurs,
inducing phase separation within the phase
boundary curve ABA. 100%Pe+ 100% Pe-

• The segmented tie line indicates a system

having an overall composition within the
two-phase region (pt C for eg.), consists of
two phases; one being polymer poor, point A
and one containing the hydrated liquid
complex, Pe- and Pe+, point B.
 Polymer-Polymer Interaction
• Gelatin and gum arabic are typical polyelectrolytes WATER100%
that can be caused to interact. A

• Gelatin, at pH conditions below its isoelectric point, C

possesses a net positive charge, whereas the acidic B
gum arabic is negatively charged. D

• Under proper pH, temp. and concentrations the

two polymers can interact through their opposite
electrical charges, forming a complex that exhibits
phase separation/coecervation.
• The water immiscible liquid, methy salicylate is an
100%Pe+ 100% Pe-

example of the drug to be encapsulated.

• Aqueous solutions of gum arabic and pigskin gelatin
(isoelectric point 8.9) are prepared each 2% by wt in
conc.
• The homogenous solutions are mixed together in
equal amounts and diluted to twice their vol. with
water and pH adjusted to 4.5and warmed to 40 -45oC
 Polymer-Polymer Interaction
WATER100%
• The oppositely charged macromolecules A

interact at these conditions and undergo PSC.

C
• While maintaining the warm temp. conditions,
B
the liquid core material Methyl Salicylate, is D

added. The core material is emulsified by

stirring to yield the desired drop size.
• The mixture is then slowly cooled to 25oC
with continued stirring for one hour.
• During the cooling cycle, PSC is further 100%Pe+
100% Pe-

enhanced resulting in microencapsulation of

drug with gelatin- gum arabic complex. The
coating is ridigized for drying by cooling the
mixture to about 10oC.
• Drying can be carried out by spray, freeze,
fluid bed and tray drying techniques.
 Multiorifice Centrifugal Process
• Mechanical process for producing microcapsules
that utilizes centrifugal forces to hurl, a core
material particle through an enveloping
microencapsulation membrane, thereby effecting
mechanical microencapsulation
 Multiorifice
Multiorifice Centrifugal Process
Centrifugal Process
• A rotating cylinder1 , is a major and
essential portion of the device
• Located within the cylinder are three
circumferential grooves 2,3,4
• In the intermediate groove,3, are a
number of orifices spaces closely and
circumferentially around the cylinder
• The upper and lower grooves are
located circumferentially around the
cylinder which carry the coating
material in molten or solution form
via tubes, 5, to the respective grooves
 Multiorifice Centrifugal Process
• The ridges of the coating material grooves , 2
and 4, serve as a weir over which the coating
material overflows when the volume of the
upper and lower grooves is exceeded by the
volume of material pumped into the system

• The coating material,6, under centrifugal

force imparted by the cylinder rotation, flows
outward along the side of the immediate
groove into the countersunk portion and
forms a film across the orifice

• A counter rotating disc 7, mounted within the

cylinder, atomizes or disperses the core
material fed through the centrally located
inlet 8
 Multiorifice Centrifugal Process
• The rotating disc flings the particulate
core material (liquid) droplets or (solid
particles) towards the orifices which
encounters the coating material
membrane

• The impact and centrifugal force,

generated by the rotating cylinder, hurls
the core material through the enveloping
coating membrane,9, which is
immediately regenerated by the
continually overflowing coating material

• The embryonic microcapsules, upon

leaving the orifices, are hardened,
congealed, or voided of coating solution
by a variety of means
 Multiorifice Centrifugal Process
• They can be flung into a
heated, countercurrent air
stream to harden or congealed

• The microcapsules can be

forced into a rotating
hardening or congealing bath

• The coating material, if a

melt, can be hurled into a cool
liquid (non solvent for coating
material) decreasing the
temperature below the
melting point of the coating