Microencapsulation

Techniques
Definition

• 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 product obtained by this process is called as Microcapsules.

Fundamental Consideration
• Generally Micro particles consist of two components
• a) Core material.
• b) Coat or wall or shell material
• Core Material
• The material to be coated.
• It may be liquid or solid or gas.
• Liquid core may be dissolved or dispersed material.
• Composition of core material
• Drug or active constituent
• Additive like diluents
• Stabilizers
• Coating Material
• Inert substance which coats on core with desired thickness.
• Composition of coating:
• Plasticizer
• Coloring agent
• Resins,
• waxes
• and lipids
• Release rate enhancers or retardants
• Examples of Coating Materials
• 1. Water soluble resins- Gelatin, Gum Arabic, Starch, PVP, CMC, .
….MC, Polyvinyl alcohol.
• 2. Water insoluble resins- EC, Polyethylene, Polymethacrylate, … ..
Polyamide (Nylon), Cellulose nitrate, Silicones.
• 3. Waxes and lipids- Paraffin, Carnauba, Beeswax, Stearic acid, . ..
Stearyl alcohol, Glyceryl stearates.
• 4. Enteric resins- Cellulose acetate phthalate, Zein.
REASONS FOR ENCAPSULATION
• The core must be isolated from its surroundings, as
• 1. To reduce the reactivity of the core in relation to the outside
environment
• 2. To convert liquid active components into a dry solid system,
• 3. To separate incompatible components for functional reasons,
• To control the rate at which it leaves the microcapsule, as
• 1. To control release of the active components for delayed (timed)
….release or long-acting (sustained) release,
• 2. The problem may be as simple as masking the taste or odor of
….the core,
• 3. To Increase of bioavailability,
• 4. To produce a targeted drug delivery,
• 5. Protects the GIT from irritant effects of the drug,
Techniques to Manufacture Microcapsules
• The technique of microencapsulation depends on the physical and
chemical properties of the material to be encapsulated.
• The stability and the biological activity of the drug should not be
affected,
• Yield and drug encapsulation efficiency should be high,
• Microsphere quality and drug release profile should be reproducible
within specified limits,
• Microsphere should not exhibit aggregation or adherence,
• Process should be usable at an industrial scale,
Physical Methods
• :Air suspension techniques (Wurster)
• Coacervation Process
• Spray Drying & Congealing
• Pan Coating
• Solvent Evaporation
• Polymerization
• Extrusion
• Single & Double Emulsion Techniques
• Supercritical fluid Anti Solvent method (SAS)
• Nozzle Vibration Technology
• Chemical Methods:
• Interfacial polymerization
• In-situ polymerization
• Matrix polymerization
Air Suspension technique

• In this process, the drug particles are coated and dried while
suspended in an upwardly moving current of air. Solutions
and suspensions of coating materials in both water and
volatile organic solvents are employed. The drying of the
coated particles is accomplished at either room or elevated
temperatures, depending on the solvent used.
Coacervation/Phase separation technique
• Three steps process.
• Step 1: Formation of three immiscible chemical phases
• (i)a liquid manufacturing vehicle phase,
• (ii) a core material phase and
• (iii) a coating material phase.
• 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
phase separation coacervation, that is,
• By changing the temperature of the polymer solution
• By adding a salt
• By adding a non-solvent
• By adding incompatible polymer to the polymer solution
• Step 2: Depositing the liquid polymer coating upon the
core material
• This is accomplished by controlled, physical mixing of the
coating material (while liquid) and the core 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.
• Step 3: Rigidizing the coating
• This is usually done by thermal, cross linking or desolvation
techniques.
Solvent Evaporation
• In the case in which the core material is dispersed in the polymer
solution, polymer shrinks around the core.
• In the case in which core material is dissolved in the coating polymer
solution, a matrix - type microcapsule is formed.
• The core materials may be either, water - soluble or water -
insoluble materials.
• A variety of film - forming polymers can be used as coatings
• Eg. Evaluation of Sucrose Esters as Alternative Surfactants in
Microencapsulation of Proteins by the Solvent Evaporation Method.
 Core Material

Dissolved or dispersed

Coating polymer solution

With Agitation

Liquid manufacturing liquid phase

Heating if necessary

Evaporation of polymer solvent

Microencapsulation
Polymerization
• The method involve the reaction of monomeric unit located at the
interface existing between a core material substance and continuous
phase in which the core material is disperse.
• The core material supporting phase is usually a liquid or gas, and
therefore polymerization reaction occur at liquid-liquid, liquid-gas,
solid-liquid, or solid-gas interface.
• E.g., In the formation of polyamide (Nylon) polymeric reaction
occurring at liquid- liquid interface existing between aliphatic
diamine & dicarboxylic acid halide
Types of Polymerization Technique
• Interfacial polymer:
• In Interfacial polymerization, the two reactants in a
polycondensation meet at an interface and react rapidly.
• In-situ polymerization: In a few microencapsulation processes, the
direct polymerization of a single monomer is carried out on the
particle surface. e.g., Cellulose fibers are encapsulated in
polyethylene while immersed in dry toluene. Usual deposition rates
are about 0.5μm/min.
Developmental aspects of Reservoir and
Matrix system
• Two methods
• Diffusion controlled
• Dissolution controlled
• DIFFUSION CONTROLLED
• In these type of system, the rate controlling step is not dissolution
rate but the diffusion of dissolved drug through a polymeric barrier.
• Since the diffusional path length increases with time as the
insoluble matrix is gradually depleted by the drug and the release of
drug is never zero order.
• DIFFUSION CONTROLLED
• There are following type of diffusion-controlled system
• 1. Reservoir devices
• 2. Matrix devices
• 1. Reservoir devices:- Drug will partition into the membrane and
exchange with fluid surrounding the particle or tablet.
• The water-soluble polymer material encases a core of drug.
Additional drug will enter the membrane, diffuse to the periphery
and exchange with the surrounding media.
• RESERVOIR DIFFUSION CONTROLLED SYSTEM These systems are
hollow in which core of drug is surrounded in water insoluble
polymer membrane.
• Coating or microencapsulation technique are used to apply
polymer.
• The permeability of membrane depend on thickness of the
coat/concentration of coating solution & on the nature of polymer,
ethyl cellulose and polyvinyl acetate are the commonly used
polymer in such devices.
• The mechanism of drug release across the membrane involves
partitioning into the membrane with subsequent release into the
surrounding fluid by diffusion.
• The rate of drug release from the reservoir system can be explained
by Fick ’s Law of diffusion as per the following equation.

• dm/dt = DSK(ΔC)/l 6
• Where, S = is the active diffusion area.
• D = is the diffusion coefficient of the drug across the coating
membrane
• l = is the diffusional path length (thickness of polymer coat)
• ΔC = is the concentration difference across l.
• K = is the partition coefficient of the drug between polymer and the
external medium.
• There are 2 processes used to apply insoluble polymeric materials to
enclose drug containing core in tablets.
• Press coating & Air suspension techniques
• Microencapsulation process is commonly used.
• In most cases drug is incorporated in coating film as well as in the
microcapsule.
• Care should be taken during placement into tablet or capsule
dosage forms to minimize fragmentation or fusion of the particle
both effects will alter release characteristics.
Matrix diffusion Controlled system
• In these system the drug is dispersed in insoluble matrix of rigid non
swellable hydrophobic materials or swellable hydrophilic
substances.
• Insoluble plastics such as PVC and fatty materials like stearic acid,
beeswax etc are the material used for rigid matrix.
• The drug is generally kneaded within the solution of plastic material
such as PVC in an organic solvent and granulated. The wax drug
matrix is prepared by dispersing the drug in molten fat followed by
congealing.
• The release of highly water-soluble drug can be sustained by using
swellable matrix systems.
• Hydrophilic gums may be of natural origin (Guar gum, tragacanth),
semi synthetic (HPMC, CMC, Xanthan gum) or synthetic (poly acryl
amides) are the material generally used for such matrices.
• In the solvent such as alcohol the gum and drug are granulated
together and compressed into tablet.
• The mechanism of drug release from this system involves initial
dehydration of hydrogel followed by absorption of water and
desorption of drug via swelling controlled diffusion mechanism.
• As the gum swells and the drug diffuses out of it, the swollen mass
devoid of drug appear transparent or glass like and so the system is
sometimes called as glassy hydrogel.
DISSOLUTION CONTROLLED RELEASE
• These system are easiest to design.
• The drug with slow dissolution rate is inherently sustained. E.g.,
Griseofulvin, Digoxin and Saliyclamide & they act as natural
prolonged release products.
• Aluminum aspirin and ferrous sulfate produce slow dissolving form
when it comes in contact with GI fluids.
• Drugs having high aqueous solubility & dissolution rate E.g.,
Pentoxifylline steroid undergo transformation into less soluble
polymorphs during dissolution in absorption pool.
• Dissolution controlled release products are divided in two classes:
• 1) Encapsulation dissolution control.
• 2) Matrix dissolution control.
• 1. Encapsulation/Coating dissolution-controlled system (Reservoir
Devices)
• Encapsulation involves coating of individual particles, or granules of
drug with the slowly dissolving material.
• The particles obtained after coating can be compressed directly into
tablets as in spacetabs or placed in capsules as in the spansule
products.
• Encapsulation/Coating dissolution-controlled system (Reservoir
Devices)
• As the time required for dissolution of coat is a function of its
thickness and the aqueous solubility of the polymer one can obtain
the coated particles of varying thickness in the range of 1- 200
micron.
• By using one of several microencapsulation techniques the drug
particles are coated or encapsulated with slowly dissolving
materials like cellulose, PEGs, olymethacrylates, waxes etc.
• Two methods of preparation are employed
• 1. Granule coating
• 2. Microencapsulation
• Granule Coated Products :
• Procedure:
• Non pareil seeds are coated with drug
• This followed with by a coat of slowly dissolving material such as
carbohydrate sugars & cellulose , PEG , polymeric material & wax.
• Coated granules can be placed in a capsule for administration. E.g.
amobarbital & dextroamphetamine sulfate
• Microencapsulation :
• This method can be used to encase liquids , solids , or gases. E.g.
aspirin & potassium chloride
• Advantage of this method is that sustained drug release can be
achieved with taste abatement & better GI tolerability.
• Encapsulation/Coating dissolution controlled system
• MICROENCAPSULATION PROCESSES that are used for the
preparation are
• COASERVATION/ PHASE SEPARATION
• INTERFACIAL
• PRECIPITATION
• SALTING OUT
• SOLVENT EVAPORATION
Matrix (or Monolith)/ Embedded
dissolution-controlled system.
• Since the drug is homogeneously dispersed throughout a rate
controlling medium matrix system are also called monoliths.
• The waxes used for such system are beeswax, carnauba wax,
hydrogenated castor oil etc.
• These waxes control the drug dissolution by controlling the rate of
dissolution fluid penetration into the matrix by altering the porosity
of tablet, or by itself dissolved at a slower rate.
Matrix (or Monolith)/ Embedded
dissolution-controlled system
• The dispersion of drug wax is prepared by dispersing the drug in the
molten wax followed by congealing and granulating the same.
• The process, compression parameters and size of particles formed
determine the release rate from this system. The drug release is
often first order from such matrices.
EROSION CONTROLLED DRUG DELIVERY
SYSTEM
• Erosion is defined as the disintegration of the polymer/ wax matrix,
as a result of degradation and is characterized by material loss from
the polymer generally in the physical state.
• Polymer or wax degradation or hydrolysis is brought by enzyme, pH
change or due to osmotic pressure or hydrodynamic pressure that
causes fragmentation.
• Erosion is affected by external stimuli; such systems can be
classified under stimuli activated drug delivery system.
• It is classified on the type of stimuli:
• 1. Physical e.g. (osmotic pressure)
• 2. Chemical e.g.(pH)
• 3. Biological e.g. (enzyme)
• Examples of erodible matrices include hydrophobic materials ethyl
cellulose and waxes.
• Depending on the erosion mechanism, polymer or waxes undergo
either surface erosion or bulk erosion
• SURFACE EROSION:
• It occurs from the surface layers of the device only.
• It results in gradual decrease in the size of the device while the bulk
phase remain un-degraded.
• There is a difference in erosion rate between the surface and centre
of matrix, the process is also called as heterogeneous erosion.
• Surface erosion occurs when water penetration is restricted to
device surface.
• BULK EROSION:
• It occurs throughout the polymer bulk and the process is thus
called as homogenous erosion.
• Bulk erosion occurs when the water is readily able to penetrate the
matrix of the device.