MICROENCAPSULATION

PRAWAN DAHAL
 Introduction
• Microencapsulation is a process by which solids, liquids or
even gases may be enclosed in microscopic particles
formation of thin coatings of wall material around the
substances.
• 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.
• Microencapsulation includes Bio encapsulation which is more
restricted to the entrapment of a biologically active substance
(from DNA to entire cell or group of cells for example)
generally to improve its performance &/or enhance its shelf
life.
 Introduction
• Microencapsulation provides the means of
converting liquids to solids, of altering
colloidal and surface properties, of providing
environmental protection and of controlling
the release characteristics or availability of
coated materials.
Microencapsulation process
 Advantages
• Can be used for converting liquid drugs in a free flowing powder.
• The drugs, which are sensitive to oxygen, moisture or light, can
be stabilized by microencapsulation.
• Incompatibility among the drugs can be prevented.
• Vaporization of many volatile drugs e.g. methyl salicylate and
peppermint oil can be prevented.
• Many drugs have been microencapsulated to reduce toxicity and
GI irritation including ferrous sulphate and KCl.
• Alteration in site of absorption can also be achieved.
• Toxic chemicals such as insecticides may be microencapsulated
to reduce the possibility of sensitization of factorial person.
• Microencapsulation can be used to enhance stability eg:
vitamin A palmitate
 Reasons for microencapsulation
• The reasons for microencapsulation are countless. In
some cases,
– the core must be isolated from its surroundings, as in isolating
vitamins from the deteriorating effects of oxygen,
– retarding evaporation of a volatile core,
– improving the handling properties of a sticky material,
– isolating a reactive core from chemical attack.
– to control the rate at which it leaves the microcapsule, as in the
controlled release of drugs or pesticides.
– To mask the taste or odor of the core,
– Increasing the selectivity of an adsorption or extraction process.
 Core materials
• The core material, defined as the specific material to be
coated, 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
materials.
• The solid core be active constituents, stabilizers, diluents,
excipients, and release-rate retardants or accelerators.
• The ability to vary the core material composition provides
definite flexibility and utilization of these characteristics
often allows effectual design and development of the
desired microcapsule properties.
 Coating materials
• The selection of appropriate coating material decides the
physical and chemical properties of the resultant
microcapsules/microspheres.
• While selecting a polymer the product requirements ie.
Stabilization, reduced volatility, release characteristics,
environmental conditions, etc. should be taken into
consideration.
• Generally hydrophilic polymers, hydrophobic polymers (or)
a combination of both are used for the
microencapsulation process.
• Examples include gelatin, polyvinyl alcohol, ethyl cellulose,
cellulose acetate phthalate and styrene maleic anhydride.
• 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.
• The microcapsules may consist of a single particle or clusters of
particles.
• After isolation from the liquid manufacturing vehicle and drying, the
material appears as a free flowing powder.
• The powder is suitable for formulation as compressed tablets, hard
gelatin capsules, suspensions, and other dosage forms.
• The coating material should be capable of forming a film that is
cohesive with the core material; be chemically compatible and
nonreactive with the core material; and provide the desired coating
properties, such as strength, flexibility, impermeability, optical
properties, and stability.
• The coating materials used in microencapsulation methods are
amenable, to some extent, to in situ modification
 Coating material properties
• Stabilization of core material.
• Inert toward active ingredients.
• Controlled release under specific conditions.
• Film-forming, pliable, tasteless, stable.
• Non-hygroscopic, no high viscosity, economical.
• Soluble in an aqueous media or solvent, or
melting.
• The coating can be flexible, brittle, hard, thin etc.
 Examples of coating materials:
• Water soluble resins –
– Gelatin, Gum Arabic, Starch, Polyvinylpyrrolidone,
Carboxymethylcellulose, Hydroxyethylcellulose, Methylcellulose,
Arabinogalactan, Polyvinyl alcohol, Polyacrylic acid.
• Water insoluble resins
– Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide (Nylon),
Poly (Ethylene Vinyl acetate), cellulose nitrate, Silicones, Poly
lactideco glycolide.
• Waxes and lipids
– Paraffin, Carnauba, Spermaceti, Beeswax, Stearic acid, Stearyl alcohol,
Glyceryl stearates.
• Enteric resins
– Shellac, Cellulose acetate phthalate, Zein
Techniques to manufacture microcapsules
• Preparation of microspheres should satisfy certain
criteria:
– The ability to incorporate reasonably high concentrations
of the drug.
– Stability of the preparation after synthesis with a clinically
acceptable shelf life.
– Controlled particle size and dispersability in aqueous
vehicles for injection.
– Release of active reagent with a good control over a wide
time scale.
– Biocompatibility with a controllable biodegradability and
Susceptibility to chemical modification
 Coacervation and microencapsulation
• Coacervation is a colloid phenomenon. If one starts with a solution of
a colloid in an appropriate solvent, then according to the nature of the
colloid, various changes can bring about a reduction of the solubility
of the colloid.
• As a result of this reduction a large part of the colloid can be
separated out into a new phase. The original one phase system
becomes two phases. One is rich and the other is poor in colloid
concentration.
• The colloid-rich phase in a dispersed state appears as amorphous
liquid droplets called coacervate droplets. Upon standing these
coalesce into one clear homogenous colloid-rich liquid layer, known as
the coacervate layer which can be deposited so as to produce the wall
material of the resultant capsules.
• Coacervation may be initiated in a number of different
ways. Examples are changing the temperature, changing
the pH or adding a second substance such as a
concentrated aqueous ionic salt solution or a non-solvent.
• As the coacervate forms, it must wet the suspended core
particles or core droplets and coalesce into a continuous
coating for the process of microencapsulation to occur.
• The final step for microencapsulation is the hardening of
the coacervate wall and the isolation of the microcapsules,
usually the most difficult step in the total process.
• This process consists of three Steps-
– Formation of three immiscible phases; a liquid manufacturing
phase, a core material phase and a coating material phase
– Deposition of the liquid polymer coating on the core material
– Rigidizing of the coating material
• Step-1: The first step of coacervation phase
separation involves the formation of three immiscible
chemical phases: a liquid vehicle phase, a coating
material phase and a core material phase.
• The three phases are formed by dispersing the core
material in a solution of coating polymer, the vehicle
phase is used as a solvent for polymer.
• The coating material phase consists of a polymer in a
liquid phase, is formed by using one of the of phase
separation-
– coacervation method, i.e. .by changing the temperature of
the polymer solution,
– by adding a solution, or
– by inducing a polymer- polymer interaction.
• Step-2: It involves the deposition of the liquid
polymer coating upon the core material. This is
done by controlled mixing of liquid coating
material and the core material in the
manufacturing vehicle.
• The liquid coating polymer deposited on the core
material if the polymer is adsorbed at the
interface formed between the core material and
liquid phase. The reduction in the total free
interfacial energy of the system help to promote
the deposition of the coating material, brought by
the decrease of the coating material surface area
during coalescence of the liquid polymer droplets.
• Step-3: In the last step rigidizing of the coating material done by
the thermal, cross linking desolvation techniques, to forms a self
supporting microcapsule.

Fig. (a) Core material

dispersion in solution
of shell polymer;
(b) Separation of
coacervate from
solution;
(c) Coating of core
material by micro
droplets of
coacervate;
(d) Coalescence of
coacervate to form
continuous shell
around core
particles.
COACERVATION - PHASE SEPARATION
 COACERVATION - PHASE SEPARATION

1. TEMPERATURE CHANGE METHOD

• Change in temperature causes separation of
coating material from the solvent
• Useful when the solubility of the material
depend on temperature
E.g. Coatng mat.: Ethyl cellulose in cyclohexane
( EC is insoluble in Cyclohexane at room temp.)
Core Material: N-Acetyl P-Amino Phenol
Temperature Change Method
 [Link] POLYMER ADDITION
• The polymer which is chemically not compatible will
be added to the coating solution .
• The polymer which is to be added should have
 More affinity towards solvents
 No interaction with the core material
 Incompatible with the coating material

E.g: Addition of liq. Polybutadiene (Incompatible

polymer) to the EC solution in toluene (Coating sol.).
Core material: Methylene blue HCl.
[Link] POLYMER ADDITION
 3. SALT ADDITION
• Soluble inorganic salts can be added to aqueous
solutions of certain polymers
• The salt added should
 Be soluble in water
 Should precipitate the polymer from the solution
 Not have any interactions with a core material
Eg: Addition of 20% Sod. Sulfate to the gelatin
solution.
Core Mat.: Oil soluble vitamin in corn oil.
3. SALT ADDITION
 4. NON-SOLVENT ADDITION
• Phase separation can be induced by addition of non-solvent
for given polymer
• The non-solvent used should
 Have more affinity towards solvent which is used
 Precipitate the coating polymer
 Not have any affinity towards core materia
• Eg: Addition of Isopropyl ether to Cellulose acetate butyrate
(CAB) dissolved in Methyl ethyl ketone.
• Core Mat: Methyl Scopolamine HBr.
4. NON-SOLVENT ADDITION
 5. POLYMER- POLYMER INTERACTION
(COMPLEX COACERVATION):
• Based on the ability of cationic and anionic water
soluble polymers to interact in water to form a liq,
polymer rich phase complex coaservate
Eg: gelatin below its isoelectric pH possess + ve charge,
gum Arabic is – ve ly charged.
Core mat: Methyl Salicylate.
• Microcapsules of 20-800µm size will be obtained
• The microcapsule shells are moisture sensitive
5. POLYMER- POLYMER INTERACTION
(COMPLEX COACERVATION):
COMPLEX COACERVATION
WURSTER PROCESS:
 PROCESSING VARIABLES IN
WURSTER PROCESS
 Core material: Density, S.A, M.P, Solubility,
Friability, Volatility, Crystallinity & Flowability.
 Concentration of coating material.
 Amount of coating material required.
 Coating material application rate.
 Inlet and outlet operating temperatures.
 Volume of air required to support and fluidize
the core material.
MULTIORIFICE CENTRIFUGATION

• By using centrifugal forces for encapsulating

liquids & solids
• Rotating cylinder
• 3 Circumferential Grooves
• Intermediate groove with orifice
• Tubes to carry coating material to upper &
lower groove.
• Counter rotating disc- Atomizes/Disperses
cores.
 PROCESSING VARIABLES

• Rotational speed of Cylinder

• Flow rate of Core & coating material
• Concentration & viscosity of coating material
• Viscosity & Surface tension of core material
 PAN COATING

• Used for large size particles i.e 600-5000 μm

size
• Coating solution is applied as a solution or
atomized spray on sugar pellets (Non-pareil
sugar seeds)
• Warm air is passed to remove the coating
solvent
• Coating pan is used for this operation
SOLVENT EVAPORATIONS

Active
Ingredient
Polymer
+ Volatile organic solvent
Step 1:
Formation of a solution/dispersion of
the drug into an organic polymer
Organic Polymeric Phase phase.
Addition into an aqueous
phase (+o/w stabilizer)
Step 2:
Formation of Oil-in-Water
Emulsification of the
Emulsion polymer phase into an aqueous phase
containing a suitable stabilizer, thus,
Temperature increase
forming a o/w emulsion.
Solvent Evaporation
Step 3:
Removal of the organic
Particle Formation by Polymer solvent from the dispersed phase by
Precipitation
extraction or evaporation leading to
polymer precipitation and formation
RECOVERY OF POLYMERIC of the microspheres.
MICROPARTICLES
SPRAY DRYING & CONGEALING (COOLING)

Spray drying : spray = aqueous solution / Hot air

Spray congealing : spray = hot melt/cold air: Thermal

congealing/Solidification of coating by introducing coating-core
mixture in to non-solvent.
POLYMERIZATION:

Drug
Monomer(s) (e.g. acrylamide, methacrylic acid) Monodisperse microgels in the micron or
+ Cross-linker (e.g. methylenebisacrylamide)
submicron size range.

Preparation of the
Polymerization Mixture Alcohol
Precipitation polymerization starts from
Addition of the alcoholic solution
a homogeneous monomer solution in
of the initiator (e.g., AIBN) which the synthesized polymer is
insoluble.
Initiation of Polymerization

The particle size of the resulting

8 hrs Reaction time
microspheres depends on the
polymerization conditions, including the
Monodisperse Latex
Formation by Polymer monomer/co monomer composition, the
Precipitation
amount of initiator and the total monomer
T (reaction) = 60 °C
concentration.
Nitrogen Atmosphere

RECOVERY OF POLYMERIC
MICROPARTICLES
INTERFACIAL POLYMERIZATION
EXTRUSION:
• This method was first patented in 1957.

• The advantage of extrusion is that it completely surrounds the core

material with wall material.

• The process involves forcing a core material dispersed in a molten

carbohydrate mass through a series of dies, into a bath of dehydrating
liquid.

• When contact with the liquid is made, the carbohydrate case hardens to
entrap the core material.

• The extruded filaments are separated from the liquid bath, dried using an
anti-caking agent such as calcium tripolyphosphate and sized .

• This process is particularly useful for heat labile substances such as

flavours, vitamin C and colours.
SINGLE EMULSION TECHNIQUE :
DOUBLE EMULSION TECHNIQUES:
NOZZLE VIBRATION TECHNOLOGY :
SAS METHOD :
 EVALUATION OF MICROCAPSULES
 Stability testing
 Size of microcapsules- Sieving Method
 Amount of drug present In microcapsules
 Dissolution test- Invitro drug release
APPLICATION OF MICROENCAPSULATION TECHNIQUES:
CONCLUSION:

• The microencapsulation technique offers a variety of opportunities such as

protection and masking, reduced dissolution rate, facilitation of handling,
and spatial targeting of the active ingredient.

This approach facilitates accurate delivery of small quantities of potent

drugs, reduced drug concentrations at sites other than the target organ or
tissue and protection of labile compounds before and after administration
and prior to appearance at the site of action.

• In future by combining various other approaches,microencapsulation

technique will find the vital place in novel drug delivery system.
 ASSIGNMENT
• Write the purpose of micro encapsulation with
examples. (with features on vitamin A
palmitate and other examples)

• Refer: Lachman for examples

THANK YOU