Dr.

Talib Hussain
MICROENCAPSULATION PhD Pharmaceutics
Lecturer, IPS, UVAS, Lahore.
 MICROENCAPSULATION
These are small particles of liquid, solids, solutions, dispersions or mixtures
that contain an active substance as a core and a synthetic or natural polymer
as a coat of varying thickness having size range of several tenth of micron to
5000 microns or (generally speaking 03-800µm).
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 materials.
The products obtained by this process is called as micro particles,
microcapsules, microsphere, coated granules, pellets etc.
Microencapsulation is method of wrapping small entities in individual
coatings designed to protect, separate or aid in storage.
 ADVANTAGES
The purpose of microencapsulation is
❖ Environmental protection of drugs to increase stability,
❖ Gastric irritation reduction and taste order masking (to improve
patient's compliance),
❖ Liquid-solid conversion, Separation of incompatibilities,
❖ Controlling or sustaining the release of drug,
❖ And minimizing or eliminating the side effects.
 MICROSPHERES VS MICROCAPSULES
Microcapsules can be generally
termed as
1. Microparticles: Contain the shell
around the core or having many
cores enclosed with in shell.
2. Microspheres: These are matrix of
drug and polymer, drug distributed
homogeneously into the shell
material.
 CLASSIFICATION
Microcapsules can be classified into three type.
1. Mono nuclear: Contain the shell around the core.
2. Po1y nuclear: Having many cores enclosed with in shell.
3. Matrix type: Distributed homogeneously into the shell material.
 CLASSIFICATION
.
HISTORY OF MICROENCAPSULATION
❖FANGER stated

❖Creation of living cell as beginning of microencapsulation

❖One-celled animals (Unicellular organisms) are living examples of

microencapsulation

❖Chicken egg have a protective wall thick enough to protect contents and
thin enough to allow breakage at hatching
 CORE AND COAT MATERIALS
❖ Core Material:

❖ The material or drugs to be coated for microencapsulation is core material.

❖ It may be liquid or solid or gas or liquid slurries or suspensions or emulsion droplets.

❖ Composition of core material:

❖ Drug or active constituent

❖ Additive like diluents

❖ Stabilizers
 CORE AND COAT MATERIALS
❖Coat/Wall Material:
❖Coating materials can be selected from wide range of material and
synthetic polymers depending on core material to be encapsulated.
❖The amount of coating material ranges from 3% to 30% of the total
weight that corresponds to a dry film thickness of less than 1-200 µm.
MICROENCAPSULATION TECHNIQUES
1) Air suspension techniques (Wurster Air Suspension)

2) Coacervation process

3) Solvent-solvent dispersion/evaporation method

4) Interfacial Polymerization techniques

5) Spray drying & spray congealing

6) Pan coating
 AIR SUSPENSION TECHNIQUE
❖This process is also known as Wurster Air Suspension (Dale E. Wurster)
and is based on Fluidized bed coating process.

❖The Wurster process consists of the dispersing of solid, particulate core

materials in a supporting air stream and the spray-coating of the air
suspended particles.

❖Micron or submicron particles can be effectively encapsulated by air

suspension techniques.
AIR SUSPENSION TECHNIQUE
It consist of dispersing the solid particulate
core material in supporting air stream and
being coated with coating material (usually
polymeric solution)

The design of the chamber and its operating

parameters effect a recirculating flow of the
particles through the coating zone portion of
the chamber, where a coating material,
usually a polymer solution, is spray applied
to the moving particles
 CONT.…
❖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
stream that is designed to induce a cyclic flow of the
particles past the spray nozzle.
❖The fine core materials are suspended in a vertical
current of air and sprayed with the coating material
❖The nozzle sprays an atomized flow of coating that
after evaporation of solvent, allows a layer of
encapsulating material is deposited on core
❖The cyclic process is repeated, perhaps several
hundred times during processing, depending on the
coating thickness desired or whether the core material
particles are thoroughly encapsulated.
❖Wruster Process can be used to encapsulate vitamins,
minerals, and functional food ingredients.
WURSTER AIR SUSPENSION INSTRUMENT
 COACERVATION
❖Coacervation was term used to describe the phenomenon of phase
separation in colloidal systems
❖Phase separation was related to precipitation or flocculation of colloidal
material from solution and coacervation (colloidal rich solution) was the
step taking place just before precipitation from solution
❖Word coacervation comes from latin, acervus meaning aggregates and
prefix co, signifying the union of colloidal particles.
❖The deposition of this coacervate around individual minute insoluble
particles dispersed in liquid form capsules that on gelling results in the
formation of microcapsules.
 COACERVATION
❖Coacervation microencapsulation is the phase separation of one or
many hydrocolloids from the initial solution and the subsequent
deposition of the newly formed coacervate phase around the active
ingredient suspended or emulsified in the same reaction media.
❖Coacervation is typically used to encapsulate flavor oil and can also be
adapted for the encapsulation of fish oils, nutrients, vitamins,
preservatives, enzymes and drugs.
❖There are two methods for coacervation, namely aqueous and organic
phase separation. Aqueous is termed as simple and complex
coacervation.
 PHASE BOUNDARY TRIANGULAR
DIAGRAMS
❖ Phase separation involves preparation of phase boundary triangular
diagrams to obtain optimum concentrations/compositions within the
coacervate region.
❖ Coacervation can be achieved by temperature change, nonsolvent addition,
salt addition, incompatible polymer addition, polymer-polymer interaction.
❖ TEMPERATURE CHANGE:
❖ Phase separation of dissolved polymer takes place in the form of
immiscible liquid droplets on changing temperatures.
❖ The droplets surround the core and form microcapsules.
❖ As the solvent of the polymer rich phase evaporates, gelation and
solidification takes place.
❖ Ethyl-cellulose and cyclohexane at high temperature is an example.
PHASE BOUNDARY TRIANGULAR DIAGRAMS
 SALT ADDITION
❖Soluble inorganic salts can be added to aqueous solutions of water-
soluble polymers to cause phase separation.
❖A gelatin-water-sodium sulphate system is an example of salt addition.
❖In this system, phase separation/coacervation is induced by adding
dropwise 20% solution of sodium sulphate.
NONSOLVENT ADDITION
❖A liquid that does not dissolve the given polymer, can be added to a
solution of the polymer to cause phase separation.
❖This immiscible liquid polymer can be utilized to encapsulate an
immiscible core.
POLYMER-POLYMER INTERACTION
❖ The addition of oppositely charged polyelectrolytes can result in the
formation of complex having educed solubility to cause phase separation.
❖ Gelatin and acacia are examples of oppositely charged polyelectrolytes as
gelatin has positive charge while acacia has negative charge.
❖ Gelatin-gelatin, gelatin-CMC, gelatin-Gantrez, Carbopol-CMC are other
examples.

INCOMPATIBLE POLYMER ADDITION

❖The incompatibility of different polymers present in same solvent can
be used for microencapsulation.
❖Methylene blue-ethylcellulose-liquid polybutadiene
 COACERVATION METHODS
AQUEOUS COACERVATION METHOD
❖Used for encapsulation of water insoluble materials (liquid or solid)
1) Hydrophilic polymeric solution is prepared in the aqueous medium
2) Hydrophobic core material is dispersed in the aqueous medium
3) Change in temperature (reduction), pH change, or addition of a
precipitating agent will cause salting out of polymeric material
4) The precipitated polymer will deposit on the dispersed core during
precipitation that will form microcapsules after gelation.
5) It is divided to Simple (one colloidal solute) and Complex (more
than one colloids) coacervation.
 SIMPLE AQUEOUS COACERVATION
❖Accomplished by addition of chemical compounds with a high affinity
for water, such as salts and alcohols.
❖All aqueous polymeric solutions can result in simple coacervation if
temperature, pH, solvent, and salt are properly chosen.
1) Hydrophilic polymeric solution is prepared in the aqueous medium
2) Hydrophobic core material is dispersed in the aqueous medium
3) Creation of insufficiency of water for the hydrophilic colloid
4) Deposition of the coacervate around the core
5) Gelation of the coacervate and hardening of microcapsules
SIMPLE AQUEOUS COACERVATION
 COMPLEX AQUEOUS COACERVATION
❖Neutralization of the charges on two colloids can result in complex
coacervation that depends on pH.
❖It can be done by mixing two colloids of opposite charges together
1) Preparation of hydrophilic colloidal solution in aqueous medium
separately for both the colloids
2) Hydrophobic core material is dispersed in one of colloidal solution
3) Addition of second hydrophilic colloid solution of opposite charge
4) Coacervation induced will be deposited around the core
5) Gelation of the coacervate and hardening of the microcapsules
 COMPLEX AQUEOUS COACERVATION
❖A combination of acacia and gelatin at neutral pH (blow isoelectric
point of gelatin).
❖Gelatin carries positive charge owing to protonation of basic groups
❖Acacia carries a negative charge because of the ionization of
glucuronic acid
❖Both hydrocolloids attract each other and separate as liquid gel phase
that fall on the dispersed core material.
❖Gelatin acacia gel can be stabilized by chemical crosslinking by
Glutaraldehyde.
COMPLEX AQUEOUS COACERVATION
ORGANIC COACERVATION METHOD
❖ Inverse of aqueous phase separation
❖ Polymeric material is hydrophobic and core is hydrophilic in nature
❖ Enclose water soluble material with a polymer in an organic solvent by
adding a nonsolvent (second organic solvent) or anther polymer to induce
coacervation.
❖ The amount and state of polymer separated depends on polymer
concentration, amount of nonsolvent added, and temperature.
❖ Examples
❖ Different viscosity grades of ethyl cellulose
❖ Polylactic acid (PLA), polyglycolic acid (PGA) and copolymer (PLGA)
 SOLVENT EVAPORATION METHOD
❖This process is carried in a manufacturing liquid vehicle that results in
microencapsulation
❖The coating material or polymers are dissolved in a volatile solvent so
that on evaporation polymer layer can be obtained
❖The core materials or drug is dissolved or dispersed in the polymeric
solution so that coating material can either cover drug particles
(reservoir) or form a mixture with drug particles (matrix)
❖The volatile solvent containing both core and coat should be dispersed
in a liquid manufacturing vehicle that is immiscible with solvent
❖The rate of agitation will demonstrate the size of microparticles formed
❖This mixture is then heated till the volatile solvent containing drug and
polymer evaporates to leave behind solid dispersion of microparticles
 SOLVENT EVAPORATION METHOD
❖In the case in which the core material is dispersed in the polymer
solution, polymer shrinks around the core (microcapsule).
❖In the case in which core material is dissolved in the coating polymer
solution, a matrix - type microcapsule is formed (microsphere).
❖The core materials may be either water soluble or water insoluble.
❖A variety of film forming polymers can be used as coatings.

❖Published Example: Microencapsulation of proteins by sucrose esters

as alternative surfactants using solvent evaporation method.
SOLVENT EVAPORATION METHOD
Core material
Dissolved or Dispersed
Coating polymer solution
With Agitation
Liquid Manufacturing Vehicle Phase
Heating (If necessary)
Evaporation of Polymer solvent

Microencapsulation
SINGLE EMULSION SOLVENT EVAPORATION
Step 1:
Formation of a solution/dispersion of
the drug into an organic polymer
phase.
Step 2:
Emulsification of the polymer phase
into an aqueous phase containing a
suitable stabilizer, thus, forming a
o/w emulsion.
Step 3:
Removal of the organic solvent from
the dispersed phase by extraction or
evaporation leading to polymer
precipitation and formation of the
microspheres.
DOUBLE EMULSION SOLVENT EVAPORATION
DOUBLE EMULSION SOLVENT EVAPORATION
 INTERFACIAL POLYMERIZATION
❖This microencapsulation method utilizes polymerization techniques to
from protective microcapsule coatings in situ.
❖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
❖Interfacial Polymerization: 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. Coating thickness
ranges 0.2-75μm.
❖Matrix polymerization: In a number of processes, a core
material is imbedded in a polymeric matrix during formation of
the particles. Prepares microcapsules containing protein
solutions by incorporating the protein in the aqueous diamine
phase.
MATRIX VS INTERFACIAL POLYMERIZATION
 IN SITU POLYMERIZATION
The microcapsule by in situ polymerization (coming only from the
aqueous phase) constitute following steps.
1. Dispersion of the liquid to be encapsulated in water
❖ In a stirred tank, the liquid to be encapsulated is dispersed in water.
The size of the droplets obtained is regulated by the speed of the
stirrer.
2. Introduction of the monomers A and B into the solution
❖ Monomers which are small molecules are then introduced into the
stirred tank, they will form a polymer by so-called polymerization
chemical reactions.
3. Initiation of the polymerization process
❖ The polymerization reaction is initiated by PH changes (acids or
bases are introduced) or / and temperature can be accelerated by the
use of catalysts. The polymer formed is deposited around the drops
which leads to encapsulation
 IN SITU POLYMERIZATION
4. Stabilization of the polymer structure
❖The polymer is then consolidated by changes in pH or
temperature or the addition of additives (crosslinking). This
leads to better isolation of the encapsulated. The finishing
operations are then carried out, they consist in adjusting the
acidity of the medium, as well as the viscosity.
❖Hard microcapsules, very tight and chemically resistant, with a
diameter of 1 to 100 μ, release drug by mechanical breakage of
the envelope, dispensed in the form of slurry or powder
 INTERFACIAL POLYMERIZATION
The microcapsule by in situ polymerization (coming only from
the aqueous phase) constitute following steps.
1. Dissolution of a monomer A in the product to be
encapsulated
❖In a stirring tank, this monomer mixture A is dispersed and the
active ingredient is encapsulated in water. The size of the
droplets obtained is regulated by the speed of the stirrer.
2. Introduction into the stirred tank of a monomer B
❖Monomer B is then introduced into the stirred tank. The
monomers, which are small molecules, will form a polymer
by chemical polymerization reactions.
 INTERFACIAL POLYMERIZATION
3. The polymerization reaction
❖The polymerization reaction takes place by a chemical reaction
which occurs between the monomers A and B. It is initiated by
changes in PH (acids or bases are introduced) or/and temperature. It
can be accelerated by the use of catalysts. The polymer formed is
deposited around the drops which leads to encapsulation.
4. Stabilization of the polymer structure
❖The polymer is then consolidated by changes in pH or temperature
or the addition of additives (crosslinking). This leads to better
isolation of the encapsulated asset. The finishing operations are then
carried out, they consist in adjusting the acidity of the medium, as
well as the viscosity.
 Interfacial Polymerization In- Situ Polymerization

❖ The multifunctional monomer dissolved ❖ In this process no reactive agents are

in liquid core material which will be added to the core material.
then dispersed in aqueous phase ❖ Polymerization occurs exclusively in
containing dispersing agent. the continuous phase and on the
❖ A co reactant multifunctional amine will continuous phase side of the interface
be added to the mixture. formed by the dispersed core material
❖ This results in rapid polymerization at and continuous phase.
interface and generation of capsule shell ❖ Initially a low molecular weight
takes place. prepolymer will be formed, as time
❖ A polyurea shell will be formed when goes on the prepolymer grows in size.
isocyanate reacts with amine, polynylon ❖ It deposits on the surface of the
or polyamide shell will be formed when dispersed core material thereby
acid chloride reacts with amine. generating solid capsule shell.
 SPRAY DRYING AND SPRAY
CONGEALING MICROENCAPSULATION
❖Spray drying and spray congealing- dispersing the core material in a
liquefied coating substance and spraying. In modern spray dryers the
viscosity of the solutions to be sprayed can be as high as 300mPa.s.
❖Spray drying is effected by rapid evaporation of a solvent in which the
coating material is dissolved.
Spray Drying:
❖The coating solidification effected by rapid evaporating of solvent in
which coating material is dissolved.
Spray Congealing:
❖The coating solidification is effected by thermally congealing a molten
coating material. The removal of solvent is done by sorption, extraction
or evaporation technique.
❖ Spray drying is one of the most widely used microencapsulation techniques,
since it provides rapid evaporation of water and maintains the low temperature
in the particles.
❖ Prior to spray drying, the wall material is mixed with the suspension
containing encapsulated components through intensive homogenization
❖ Spray congealing can be accomplished with spray drying equipment when the
protective coating is applied as a melt.
❖ Core material is dispersed in a coating material melt rather than a coating
solution.
❖ Coating solidification (and microencapsulation) is accomplished by spraying
the hot mixture into a cool air stream.
❖ Spray drying/spray congealing technique has been used for drying heat-
sensitive foods, pharmaceuticals, and other substances, because of the solvent
rapid evaporation from the droplets.
❖ Compared to the other conventional microencapsulation techniques, it offers
the attractive advantage of producing microcapsules in a relatively simple
continuous processing operation.
 SPRAY DRYING MICROENCAPSULATION

❖ Microencapsulation by spray-
drying is a low-cost commercial
process, used for the
encapsulation of fragrances,
drugs and flavors.
❖ Steps:
1. Core particles are dispersed in
a polymer solution and sprayed
into a hot chamber.
2. The shell material solidifies
onto the core particles as the
solvent evaporates. ❖ The microcapsules obtained are of polynuclear or matrix type
 SPRAY DRYING AND SPRAY
CONGEALING
❖The process involves three basic steps:
1. Preparation of a dispersion or emulsion to be processed
2. Homogenization of the dispersion and
3. Atomization of the mass into the drying chamber.
❖Spray dried ingredients typically have a very small particle size
(generally less than 100µm) which makes them highly soluble.
❖Typical shell materials include gum acacia, maltodextrins,
hydrophobically modified starch and mixtures. Other polysaccharides
like alginate, carboxymethylcellulose and guar gum.
❖Proteins like whey proteins, soy proteins, sodium caseinate can be used
as the wall material in spray drying.
SPRAY DRYING AND SPRAY CONGEALING
 EVALUATION OF
MICROENCAPSULATION
Percentage Yield
❖ The total amount of microcapsules obtained will be weighed and the
percentage yield would be calculated with regards to the weight of the drug
and polymer.
❖ %𝑎𝑔𝑒 𝑦𝑖𝑒𝑙𝑑 =
𝐴𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑚𝑖𝑐𝑟𝑜𝑐𝑎𝑝𝑠𝑢𝑙𝑒 𝑜𝑏𝑡𝑎𝑖𝑛𝑒𝑑Τ𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝐴𝑚𝑜𝑢𝑛𝑡 × 100
❖ Capture Efficiency or Percentage Entrapment
❖ It is calculations for active constituents as per monograph requirement.
❖ %𝑎𝑔𝑒 𝐸𝑛𝑡𝑟𝑎𝑝𝑚𝑒𝑛𝑡: 𝐴𝑐𝑡𝑢𝑎𝑙 𝑐𝑜𝑛𝑡𝑒𝑛𝑡Τ𝑇ℎ𝑒𝑜𝑟𝑒𝑡𝑖𝑐𝑎𝑙 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 𝑥 100
❖ In-vitro drug release
❖ USP type II dissolution test apparatus can be used with microparticles
packed in tea bags and placed in phosphate buffer, sampled and analyzed.
 ESTIMATION OF DRUG CONTENTS
❖Diclofenac sodium drug content in the microcapsules can be
determined by UV spectrophotometric method.
❖A sample of microcapsules equivalent to 100 mg drug will be
dissolved in 25 ml suitable solvent (ethanol) and the volume
adjusted up to 100 ml using phosphate buffer of pH 7.4.
❖The solution will be filtered through Whatman filter paper.
❖The filtrate will assayed for drug content by measuring absorbance
at 236 nm after suitable dilution using phosphate buffer pH 7.4.
❖The drug contents can be estimated from absorbance by comparing
with calibration curve obtained by taking absorbances of known
standard dilution solution at 236 nm using UV spectrophotometer.
 PARTICLE SIZE ANALYSIS
❖For size distribution analysis, sieving method can be used by
using a set of standard sieves. The amounts retained on
different sieves weighed and calculated by using average of
sieve passed and sieve retained pore sizes.
❖Scanning Electron Microscopy (SEM)
❖Scanning electron photomicrographs of drug loaded
microcapsules could be taken by mounting/spreading a small
amount of microcapsules on gold stub and placed in the
scanning electron microscopy (SEM) chamber.
❖The SEM photomicrographs are taken at the acceleration
voltage of 20 KV