Microencapsulation

1. Guided by:
Dr. Mayur Patel
Department of
pharmaceutics
Institute of Pharmacy
Nirma University
Microencapsulation
Prepared By:
Dhara Patel
14mph103
M Pharm Sem I
Pharmaceutical
Technology and
Biopharmaceutics

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•Definition
•About
•Why???
•Classification
•Core material
•Coat material
• Mechanisms of drug release
•Techniques of preparation
•Evaluation parameters
•Applications
•Novel approaches
•Conclusion
•References
CONTENTS

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The process of
surrounding or enveloping
one substance (solid, liquid or gas)
within another substance (miniature capsule)
that can release their contents at
CONTROLLED RATES
under the influence of the specific conditions.
BIOENCAPSULATION:
Entrapment of a biologically active substance (from
DNA to entire cell or group of cells) is known as
bioencapsulation.
DEFINITION:

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•It is a process in which extremely tiny droplets,
or particles of liquid or solid material, are
packed within a second material or coated with
a continuous film of polymeric material for the
purpose of shielding the active ingredient from
the surrounding environment.
•Size : one micron to several hundred microns.
•Shape : Spherical or variably shaped
ABOUT

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•Microencapsulation provides the means of
converting liquids into solids, of altering colloidal &
surface properties, of providing environmental
protection, & of controlling the release
characteristics or bioavailability of
coated materials.
•Because of smallness of the particles, drug moieties
can be widely distributed throughout the
gastrointestinal tract.

improving drug sorption

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•For sustained or prolonged release.
•For taste masking and odour of many drugs to
improve patient compliances.
•Converting oils or other liquid drugs in a free
flowing powder.
•Drugs sensitive to oxygen, moisture or light, can be
stabilized.
•Incompatibility among the drugs can be prevented.
•Vaporization of many drugs (methyl salicylate,
peppermint oil) can be prevented.
Why???

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•To reduce toxicity and gastrointestinal irritation e.g.
FeSO
4 and KCL.
•Alteration in site of absorption can also be
achieved.
•Improvement in flow properties.
•Microencapsulated drugs have enhanced stability.
•Aid in dispersion of water insoluble drugs in
aqueous fluid.
•Production of sustained release, controlled release
& targeted medication.
•Reduced dose dumping compared to high dose
implants.

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Microcapsules
Monocored
Polycored
Matrix
(Microspheres)
Classification

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•Solid and liquid can be coated.
•Liquid core include dispersed or dissolved
material.
•Solid can be the mixture of API, diluents,
excepients, release rate retardants or
accelerators.
Core Material

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Core Material Characteristic
Technique
Purpose of
Microencapsulation
Final product
form
Acetaminophen Slightly soluble
solid
Taste masking Tablet
Activated
charcoal
Adsorbent Selective sorption Dry powder
Aspirin Slightly water
soluble solid
Taste masking,
sustained release,
reduced gastric
irritation, separation
of incompatibilities.
Tablet or Capsule
Isosorbide
dinitrate
Water soluble
drug
Sustained release Capsule
Methanol/
methyl salicylate
camphor
mixture
Volatile solution Reduction of
volatility, sustained
release.
Lotion
Vit A palmitate Nonvolatile
liquid
Stabilization to
oxidation
Dry powder

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•Capable of forming a film.
•Compatible with core material.
•Non reactive to core material.
•Inert toward active ingredients.
•Controlled release under specific conditions.
•Film-forming, pliable, tasteless, stable, flexible,
impermeable.
•Non-hygroscopic, less viscosity, economical.
•Soluble in an aqueous media or solvent.


Coat material

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Water soluble
resins
Gelatin
Gum Arabic
Starch
PVP / PVA
CMC
MC/ HPC /
HPMC
Water
insoluble
resins
EC
Polyethene
Nylon
Cellulose
nitrate
Silicones
Waxes and
lipids
Paraffin
Carnauba
Spermaceti
Beeswax
Stearic acid
Glyceryl
stearate
Enteric resins
Shellac
CAP
zein
Examples of coat material

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•Major mechanisms of drug release from
microcapsules are as follows:

1.Degradation controlled monolithic system
2.Diffusion controlled monolithic system
3.Diffusion controlled reservoir system
4.Erosion


MECHANISMS OF DRUG RELEASE

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The drug is dissolved in matrix and is distributed
uniformly throughout. The drug is strongly
attached to the matrix and is released on
degradation of the matrix. The diffusion of
the drug is slow as compared with
degradation of the matrix.


1. Degradation controlled
monolithic system

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•Here, the active agent is released by diffusion
prior to, or concurrent with the degradation of
the polymer matrix. Rate of release also depend
upon where the polymer degrades by
homogeneous or heterogeneous mechanism.

2. Diffusion controlled
monolithic system

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Here, the active agent is encapsulated by a rate
controlling membrane through which the agent
diffuses and the membrane erodes only after its
delivery is completed. In this case, drug release is
unaffected by the degradation of the matrix.
3. Diffusion controlled reservoir
system

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Erosion of the coat due to pH and enzymatic
hydrolysis causes drug release with certain coat
material like glyceryl mono stearate, beeswax
and steryl alcohol, etc.


4. Erosion

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PHYSICAL METHODS

Coacervation –Phase
separation
Coacervation Process
Air-suspension
Centrifugal extrusion
Pan-coating
Spray-drying
Rapid expansion of
supercritical fluids (RESS)
Gas anti-solvent
Particles from gas-
saturated solution
CHEMICAL
METHODS

Solvent evaporation
Interfacial polymerization
In-situ polymerization
Matrix polymer
TECHNIQUES OF PREPARATION:

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Polymeric
Membrane
Droplets
Homogeneous
Polymer Solution
Coacervate
Droplets
PHASE
SEPARATION
MEMBRANE
FORMATION
•Coacervation is based
on separation of a
solution of hydrophilic
polymer(s)into two
phases, which are small
droplets of a dense
polymer-rich phase and
a dilute liquid phase.
–Simple Coacervation.
–Complex Coacervation.
Coacervation

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Simple Coacervation
•Involves only one polymer and the phase separation
can be induced by conditions that result in
desolvation (or dehydration) of the polymer phase.
•These conditions include addition of a water-miscible
non-solvent, or addition of inorganic salts.
Complex Coacervation
•It involves two hydrophilic polymers of opposite
charges.
•When one charge get neutralized by the opposite
charge the polymer gets separated and deposits on
the droplet.
•Once coacervates form, these polymer complexes are
stabilized by cross-linking using gluteraldehyde.

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•Microparticles can be produced from emulsion
of two or more immiscible liquids.
•solution of hydrophobic drug and polymer in an
organic solvent is emulsified in an aqueous
solution containing an emulsifying agent to
produce oil in-water (o/w) emulsion.
•Depending on the solubility of the drug the type
of emulsion can be modified.
Emulsion solidification

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SOLVENT
EVAPORATION
•Polymer is dissolved
in volatile organic
solvent
•Drug is solubilized or
dispersed in polymer
solution
•Emulsified in aq
solution containing
emulsifying agent.
•Stirred till all solvent
get evaporated
•Washed and freeze
dried.
•Sometimes emulsion
is heated to evaporate
organic phase.
SOLVENT EXTRACTION
•Volatile solvents used
otherwise it results in
irregular morphology,
high porosity of the
microspheres, loss of
payload, polydispersed
•Relatively non volatile
solvent can be removed by
extraction in continuous
phase
•This is done by using
solvent that has significant
solubility in continuous
phase, increasing the
concentration difference
between continuous
phase and dispersed
phase or by adding third
solvent in continuous
phase to facilitate
extraction of solvent.
CROSS LINKING
•The hydrophilic
polymers from natural
origin such as gelatin,
albumin, starch,
dextran and chitosan
can be solidified by a
chemical or thermal
cross-linking process.
A w/o emulsion is
prepared by
emulsifying the
polymer solution in an
oil phase containing
an emulsifying agent
such as Span 80.
•Heating and adding
counter polyions or
cross-linking reagents
are alternative
crosslinking methods.

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•The polymer is first melted and then mixed with
solid drug particles or liquid drug.
•This mixture is suspended in an immiscible
solvent and heated to 5˚C above the melting
point of the polymer under continuous stirring.
• The emulsion is then cooled below the melting
point until the droplets solidify.

Hot-Melt Microencapsulation

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•Ionic gelation involves cross-linking of
polyelectrolyte's in the presence of multivalent
counter ions.
•Ionic gelation is often followed by polyelectrolyte
complexation with oppositely charged
polyelectrolyte's.
•This complexation forms a membrane of
polyelectrolyte complex on the surface of the gel
particles, which increases the mechanical strength
of the particles.
•Nowadays, it has widely been used for both cell and
drug encapsulation.
Ionic Gelation/Polyelectrolyte
Complexation

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Interfacial Polymerization
Polymerization can be terminated by adding excess non-aqueous phase.
Then additional non-aqueous phase containing acid chloride is added to the
emulsion to allow interfacial polymerization.
A non-aqueous phase containing surfactant and an aqueous phase containing
drugs and diamine are mixed to form a w/o emulsion.
Monomers can be polymerized at the interface of two immiscible substances to
form a membrane.

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•Spray drying is a single-step, closed-system
process applicable to a wide variety of
materials.
•The drug is dissolved or suspended in a suitable
solvent containing polymer materials.
•The solution or suspension is atomized into a
drying chamber.
•Microparticles form as the atomized droplets
are dried by heated carrier gas.
Spray Drying

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•Spray desolvation involves spraying a polymer
solution onto a desolvating liquid.
•For example, microparticles can be made by
spraying a PVA solution onto an acetone bath.
Here, the polymer solvent (water) is extracted
into acetone, and PVA precipitates to form solid
microparticles.
Spray Desolvation

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•In spray coating, the coating material is sprayed
onto solid drug core particles that are rotated in
a coating chamber.
a.Fluid bed coating (air suspension technique)
b.Pan coating
Spray Coating

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•It consists of
dispersing of solid,
particulate core
materials are
suspended in upward
moving air stream
and then spray-
coating of the air
suspended particles.
a. Fluid bed coating

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•Relatively large particles can be encapsulated by
pan coating.
• Size of solid particles should be greater than
600 mm to achieve effective coating using this
method.
b. Pan coating

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•The supercritical fluid method is a relatively new
method, which can minimize the use of organic solvent
and harsh manufacturing conditions taking advantage
of two distinctive properties of supercritical fluids.
Supercritical Fluid
•Utilizes the supercritical fluid (e.g., carbon dioxide) a
solvent for the polymer
Rapid Expansion of Supercritical
Solutions (RESS)
•Using the fluid as an antisolvent that causes polymer
precipitation.
Supercritical antisolvent crystallization
(SAS)

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•Here, supercritical fluid containing the active
ingredient and the shell material are
maintained at high pressure.
•These are then released at atmospheric
pressure through a small nozzle.
•Due to the sudden drop in pressure, desolvation
of the shell material takes place leading to its
deposition surrounding the active ingredient
(core) and forms a coating layer.

RAPID EXPANSION OF SUPERCRTICAL
SOLUTION (RESS)

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•This process is also called supercritical fluid antisolvent
(SAS).
•Here SCF is added to a solution of shell material + active
ingredients maintained at high pressure.
•This leads to volume expansion of the solution causing super
saturation causing precipitation of the solute occurs.
•The liquid solvent must be miscible in with SCF.
•And solute should be soluble in liquid solvent, but not
dissolve in solvent + SCF.
•This process is not suitable for encapsulation of water
soluble substances due to its low solubility in SCF.
Supercritical antisolvent
crystallization (SAS)

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EVALUATION PARAMETERS

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EVALUATION
PARAMETERS
Production
Yield
Drug Content
and Loading
Efficiency
Particle Size
Measurement
Surface
Characteriza
tion of the
Microcapsul
es
Determination
of Bulk
Density
Angle of
Repose
Zeta Potential
Study
Swelling
Property
Infrared
Absorption
Study
X-ray
Diffraction
Thermal
Analysis
In vitro Drug
Release

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Production Yield:
•%production yield= (W1 / W2)
* 100
•W1 = weight of dried
microcapsules
•W2 = sum of initial dry weight
of starting
materials.
Drug Content and
Loading Efficiency
•Drug Content can be measured
through dissolution and assay.
•Loading Efficiency = ( actual
amount of drug loaded/
theoretical amount ) * 100
Particle Size
Measurement:
•Microcapsules are suspended in
suitable solvents and measured
by laser particle size
distribution analyzer or
microscopic method.

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Surface Characterization of the Microcapsules:
•scanning electron microscope (SEM)
•electron microscopy
•scanning tunneling microscopy (STM)
Determination of Bulk Density :
•Average weight of microcapsules taken in 100 ml graduated
cylinder
•apparent volume (v) = 50 – 100 ml
•Bulk density = mass / volume
•Unit = gm/ ml
Angle of repose:
•tan Ө = h/r
Zeta Potential Study:-
•determined by Zeta Meter.

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In Vitro Drug
Release Study:
• Franz diffusion cell
• USP dissolution
apparatus (Basket)
Thermal
Analysis:
•Differential Scanning
Calorimetry (DSC)
•Thermo Gravimetric
Analysis(TGA)
•Differential
Thermometric
Analysis (DTA)

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Prolonged release dosage form.
Enteric coated dosage form.
Masking of taste.
Encapsulating volatile substances.
Oily medicines can be tableted.
Protect drugs from environmental conditions.
Reduction in hygroscopic nature.
Reduce gastric irritation of many drugs.
Prepare intrauterine contraceptive device.
For preparing multilayer tablet.
applications

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Self emulsifying oral lipid based formulation to improve oral bioavailability
of poorly water soluble drugs. E.g. Cyclosporine A
Advances in Heparin delivery.
Vesicles as tool for dermal and transdermal delivery to enhance the
penetration rate and acts as depot for sustained release of dermal active
compounds.
Lipid and polymeric colloidal carriers for ocular drug delivery.
Novel approaches

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Applications
in various
fields
Cosmetics
Adhesives
Carbonless
copy papers
Pesticides,
herbicides,
disinfectants
Powder
perfume
Scratch-n-
snuff
Textiles
Themochro
mic dyes
Phyto
sanitary
Detergence

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•Microencapsulation technology can protect active materials
against environment, stabilize them, prevent or suppress
volatilization.
•Microencapsulation technology can provide new forms and
features, thus, it can create whole new fields of
applications.
• Drug delivery has become increasingly important mainly
due to the awareness of the difficulties associated with a
variety of old and new drugs Of the many polymeric drug
delivery systems, biodegradable polymers have been used
widely as drug delivery systems because of their
biocompatibility and biodegradability.
conclusion

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1.“Encyclopedia of Pharmaceutical Technology”
by James Swarbrick; 3
rd
edition; Vol-4; Pg –
2315
2.The theory and practice of industrial
pharmacy; by Leon Lachman, Herbert A.
Liberman; 2009; Pg – 412.
3.“ Microencapsulation – Methods and
Industrial Applications” Drugs and The
Pharmaceutical Sciences; by Simon Benita
Vol– 158; 2
nd
edition.
References

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