Transcript Microencapsulation

DISOVER THE SCIENCE OF :
~MICRO ENCAPSULATION~
GROUP- 9 ( BITO )
Introduction to
Microencapsulation
Midhat Mustafa
Definition
The technique of microencapsulation depends on the physical and chemical
properties of the material to be encapsulated.
Barrett K. Green
Barrett K. Green (September
11,1906 - August 29,1997) was an
American scientist, innovator
Industry pioneer who is best
known as the inventor of
microencapsulation. Gave birth to
a whole new industry.
Green was a long-time national
cash register company (NCR)
employee (1933-1973)
Held 197 patents, and was highly
respected and honored scientist.
History
• Developed microcapsules by coacervation
• Developed a solid gelatin sphere with an il-phase as core with colourless
dye base dissolved.
Carbonless paper: The product had
three layers:
1.
2.
3.
The paper
A film of acid-sensitive dye packaged
in microcapsules and
A layer of acidic clay to develop the
dye from transparent to dark blue or
black.
Pressure from a writing implement (pen or pencil) broke the microcapsules of dye
on the underside of each sheet (except the last one); when the dye was released, it
reacted with acidic layer on the surface of the next sheet and became visible.
Components of a Microparticle
Classification on basis of Morphology:
Spherical
• with a continuous core region surrounded by
a continuous shell.
Geometrically irregular
• with a number of small droplets or particles of core
material surrounded by a matrix of the coating agent
• the core material is distributed homogeneously
into the shell material
Matrix
Shell Material
Core
Material
Core
Material
Shell
Material
Core
Material
Continuous Core/ mononuclear
microcapsule
polynuclear
Microcapsule
Matrix
microcapsule
Classification on basis of Size
• Particles having diameter between 3-8
micrometer are called microparticles or
microspheres or microcapsules.
• Particles larger than 1000 micrometer are
called macroparticles.
Reasons for Microencapsulation
1.
• To protect reactive substances from the environment
2.
• To convert liquid active components into a dry solid
system
3.
• To separate incompatible components for functional
reasons
4.
• To control release of the active components for delayed
(timed) release or long-acting (sustained) release
~PHYSICAL METHODS OF MICROENCAPSULATION~
By Sumayyah Khan
Pan Coating
• The pan coating process is amongst the oldest
industrial mechanisms used particularly in the
pharmaceutical industry for forming small, coated
particles or tablets.
• The particles are tumbled in a pan or other device
while the coating material is applied slowly.
• The pipe of the blower stretches into the pot for an
even heating distribution while the coating pan is
rotating.
Fluid Bed Coating
(Wurster Coating)
• Particles of the active ingredient, spheres
or granules, are suspended in an upwardmoving stream of air and then covered
with a spray of liquid coating material.
• The capsules are then shifted to an area
where their shells are solidified by cooling
or solvent vaporization.
• The whole cycle of suspending, spraying
and cooling is repeated until the capsule’s
walls are of the desired thickness.
• The size of the core particle for this
technique is usually large (~100 microns).
• This technique gives improved flexibility
and control as compared to pan coating.
Uses and Benefits:
Pharmaceutical Industry
Food Industry
Vitamins & Minerals
Mask unpleasant flavors
Improve stability & shelf
life
Spray Drying
• The flavor or ingredient to be encapsulated is
added to the carrier and homogenized to
create small droplets in a typical carrier: flavor
ratio of 4:1.
• The resultant emulsion is fed into the spray
dryer where it is atomized through a nozzle or
spinning wheel.
• Hot air contacts the atomized droplets,
causing the solvent to evaporate, leaving
dried particles.
• Collected through a cyclonic air stream or a
bag filter.
• It is immensely suitable for the continuous
manufacture of dry solids as either powder,
granulates or agglomerates from liquid feeds.
Advantages:
Versatile
Good control
Fluidity
Particle size
Redissolution rate
Bulk density
Mechanical
strength
Centrifugal Extrusion
• Liquid co-extrusion process utilizing nozzles consisting of concentric
orifices located on the outer circumference of a rotating cylinder.
• Liquid core material  inner orifice
• Liquid wall material  outer orifice
• Unbroken rope of core material surrounded by wall material
• As the device rotates, the rope naturally splits into round droplets
directly after clearing the nozzle.
• Walls of the droplets are solidified by cooling or gelling bath  capsules
• Capsule size (~500 microns)  rotational speed
• Typical wall materials include starch, maltodextrins, gelatin, polyethylene
glycol
• Mostly used to encapsulate flavor oils
Vibrational Nozzle
(Annular Jet)
• Core-shell encapsulation
can be done using a
laminar flow through a
nozzle and an additional
vibration of the nozzle or
liquid.
• Two concentric jets
• Rayleigh instability
• Very uniform droplets
• Lower microcapsule sizes
CHEMICAL METHODS OF
Microencapsulation
INTERFACIAL POLYMERZATION
1. Characterized by wall formation via the rapid polymerization
of monomers at the surface of the droplets or particles of
dispersed core material.
2. A multifunctional monomer is dissolved in the core material,
and this solution is dispersed in an aqueous phase.
3. A reactant to the monomer is added to the aqueous phase,
and polymerization quickly ensues at the surfaces of the core
droplets, forming the capsule walls.
Dynamics
•
Interfacial polymerization can be used to prepare bigger microcapsules, but
most commercial processes produce smaller capsules in the 20-30 micron
diameter range.
• The permeability and size of these microcapsules and the properties of the
polymer matrix can be tuned by varying the identity of the
monomers/oligomers, the presence of additives and the specific reacting
conditions used in the encapsulation such as temperature, concentration or
pH.
• Advantages: Rapid, uniform in size products.
• Setbacks: Fragility of capsule, lack of biodegradability, excessive drug
degradation.
SOLVENT EVAPORATION
STEP 1
The polymer is dissolved in a water immiscible
volatile organic solvent like dichloromethane or
chloroform, into which the core material is also
dissolved.
STEP 2
The resulting solution is added dropwise to a
stirring aqueous solution having a suitable
stabilizer like poly (vinyl alcohol) to form small
polymer droplets containing encapsulated
material.
STEP 3
Droplets hardened to produce the corresponding
polymer microcapsules. This hardening process
is accomplished by the removal of the solvent
from the polymer droplets either by solvent
evaporation (by heat or reduced pressure),or by
solvent extraction.
Active
Ingredient
Polymer
+ Volatile organic solvent
Organic Polymeric Phase
Addition into an aqueous
phase (+o/w stabilizer)
Formation of Oil-in-Water
Emulsion
Temperature increase
Solvent
Evaporation
Particle Formation by Polymer
Precipitation
RECOVERY OF POLYMERIC
MICROPARTICLES
IN SITU POLYMERIZATION
• Normal polymerization,can produce
microcapsules in the nanometer range.Has the
following types
•
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Bulk polymerization
Suspension polymerization
Emulsion polymerization
Micelle polymerization
Emulsion polymerization
• In an emulsion polymerization,surfactant, is dissolved in water until the critical
micelle concentration (CMC) is reached. The interior of the micelle provides the site
necessary for polymerization. A monomer (like styrene or methyl methacrylate) and
a water soluble free radical initiator are added and the whole batch is shaken or
stirred.
• This forms a latex
• The polymerisation begins and initially produced polymer molecules precipitate in
the aqueous medium to form primary nuclei. As the polymerization proceeds, these
nuclei grow gradually and simultaneously entrap the core material to form the final
microcapsules
LIPOSOMES
• A liposome is a tiny vesicle
generally made from
phospholipids
• They are spontaneously formed
when phospholipids are disrupted
in water
• Their diameter ranges from 25nm
to 10microns.
• Both hydrophobic and
hydrophilic active ingredients can
be entrapped.
COACERVATION
Coacervare :A coacervate is a tiny spherical droplet of assorted organic molecules
(specifically, lipid molecules) which is held together by hydrophobic forces from a surround in
Complex coacervation refers to
the phase separation of a liquid precipitate, or phase, when solutions of
two hydrophilic colloids are mixed under suitable conditions
liquid.Coacervates measure 1 to 100 micrometers across.
PHASE
SEPARATION
Homogeneous
Polymer Solution
Droplets
Coacervate
Droplets
MEMBRANE
FORMATION
Polymeric
Membrane
The general outline of the processes consists of three steps carried
under continuous agitation
Ingredient Stabilization of
processed Food.
Reduced Amount of effort for
same effect.
New Product Development
Drive For Brand Differentiation
Celeriac Growth in Functional
Food Market
MOLD CONTROL
RAW
PRESERVATIVES &
ACIDULANTS
ENCAPSULATE
IN MICROFILM
OF VEGE OIL
YEAST DESTRUCTION
COSTLY
CONTROLLRED
RELEASE
AFTER YEAST
ACTIVITY AT
60 C
Raw
Preservatives
Encapsulated
Preservatives
Sodium Bicarbonate + Acid(s)
CO2 + Salt + Water
 Inhibition of premature
interactions between
ingredients.
 Manipulated product
attributes.
Un-Cap
 Provides Freeze thaw
stability.
Warm industry milieu causes the sugary solution for
confectionery to become sticky. Sugar complexes are
encapsulated with a thin film that resist extreme moisture
uptake

Capsule Core : FeNH4(SO4)24H2O +
ascorbic acid
Capsule Coat : Polygylcerol
monostearate
Conditioned Release at 37 C
Encapsulated Acid
Raw Acid
Metal salts like Calcium Lactate are widely used for storing
meat products and rendering inhibition to animalcule.
Encapsulated Calcium Lactate provides control of calcium-protein
aggregates that form when calcium interacts with proteins present
in meat.
Heat + Time
APPLICATIONS OF MICROENCAPSULATION IN :
~THERAPEUTIC MEDICINE~
AZKA KHAN.
To obtain maximum therapeutic efficacy, drug is to be delivered:
• to the target tissue
• in the optimal amount
• in the right period of time
• there by causing little toxicity and minimal side effects
One such approach is using microspheres as carriers for drugs.
Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers
Solid biodegradable microspheres
Particle size less than 200 μm.
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.
Microspheres received much attention not only for prolonged release, but also for targeting of anticancer drugs
to the tumour.
REASONS FOR MICROENCAPSULATION
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Retarding evaporation of a volatile active ingredient.
Improving the handling properties of a sticky material
Isolating a reactive core from chemical attack
For controlled release of drugs
Masking the taste or odor of the AI
For safe handling of the toxic materials
To get targeted release of the drug
Converting liquid into solid form
Isolation of AI from its surroundings, as in isolating vitamins from the deteriorating effects of
oxygen
Preparation of microspheres should satisfy certain criteria:
• The ability to incorporate reasonably high concentrations of the drug.
• Stability of preparation af`ter 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
• Susceptibility to chemical modification
Fundamental Considerations
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•
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nature of the core and coating materials.
the microencapsulation methods
the stability and release characteristics of the coated materials.
Composition of Core Material
The core material is defined as the specific material to be coated (a biologically active substance)
The core material can be in liquid or solid in nature.
The composition of the core material can be varied as
Liquid core can include dispersed and/or dissolved material.
Solid core can be single solid substance or mixture of active constituents, stabilizers, diluents,
excipients and release-rate retardants or accelerators.
Coating Material
The selection of coating material decides the physical and chemical properties of microcapsules/microspheres.
While selecting a polymer the product requirements should be taken into consideration are:
•
stabilization
•
reduced volatility
•
control release characteristics under specific conditions.
•
environmental conditions, etc
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.
It should provide the desired coating properties such as:
•
strength and stability
•
flexibility,
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Impermeability
•
Non-hygroscopic, no high viscosity, economical
Generally hydrophilic / hydrophobic polymers /a combination of both are used for microencapsulation process.
Gelatin polyvinyl alcohol ethyl cellulose cellulose acetate phthalate etc are used.
The film thickness can be varied considerably depending on:
the surface area of the material to be coated
Other physical characteristics of the system
Morphology of Microcapsules
The morphology of microcapsules depends mainly on the
•
Core
•
Coating Material
Mononuclear (core-shell) microcapsules contain the shell around the core.
Polynuclear capsules have many cores enclosed within the shell.
Matrix encapsulation in which the core material is distributed homogeneously into the shell material.
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.
Release Mechanisms
Mechanisms of drug release from microspheres are
• Degradation controlled monolithic system
• Diffusion controlled monolithic system
• Diffusion controlled reservoir system
• Erosion
Microencapsulation of Aspirin
Materials:Aspirin, Acetone, Cyclohexane, Ethanol, Heavy liquid paraffin, ethyl cellulose, and water.
Method
Microcapsules of ethyl cellulose containing aspirin, prepared by an emulsion solvent evaporation method.
Aspirin microcapsules, prepared by dissolving polymers in an organic solvent to form a homogeneous polymer solution.
Addition of core material, aspirin in a thin stream of heavy liquid paraffin.
Agitation using a propeller mixer with the rotation speed 600 rpm.
The dispersed phase consisting of drug and polymer EC immediately transforms into fine droplets, which subsequently
solidified into rigid microcapsules due to solvent evaporation.
The liquid paraffin is decant, and the microcapsules are collected, washed twice in cyclohexane to remove any adhering
oily phase (liquid paraffin), and are air dried for at least 12h to obtain discrete microcapsules.
Formulation
Aspirin :EC
Drug: Polymer
4:1
Liquid paraffin
(ml)
60
Ethanol
(ml)
10
Ethyl cellulose
(gm)
1
• prolongs the drug release from dosage forms
• reduces adverse effects.
•Sustained release formulation of Aspirin reduced the undesired side effects, frequency of administration and
improves patient compliance.
Applications of microencapsulation
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To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc.
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 by microencapsulation.
Sustained release Aspirin preparations have been reported to cause significantly less G.I. bleeding than
conventional preparations.
A liquid can be converted to a pseudo-solid for easy handling and storage. eg. Eprazinone.
Hygroscopic properties of core materials may be reduced by microencapsulation eg. Sodium chloride.
Carbon tetra chlorides and a number of other substances e.g. . methyl salicylate and peppermint oil have been
microencapsulated to reduce their odor and volatility.
Microencapsulation has been employed to provide protection to the core materials against atmospheric effects and
has enhanced its stability. e.g. vitamin A palmitate.
Separation of incompatible substance has been achieved by encapsulation.
Drug delivery: Controlled release delivery systems
The drugs, which are sensitive to oxygen, moisture or light, can be stabilized by microencapsulation.
“Let Your Medicine Be Your Food,
And Your Food Be Your Medicine”
~HIPPOCRATES~