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Microencapsulation
1. INTRODUCTION
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 micro particles,
microcapsules.
Particles having diameter between 3 - 800μm are known as micro particles or
microcapsules or microspheres.
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Particles larger than 1000μm are known as Macro particles .
2. CLASSIFICATION OF MICROPARTICLE
Generally Micro particles consist of two components
a) Core material
b) Coat or wall or shell material.
1.Microcapsules: The active agent forms a core surrounded by an inert diffusion barrier.
2.Microspheres: The active agent is dispersed or dissolved in an inert polymer.
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4. ADVANTAGES:
To Increase of bioavailability
To alter the drug release
To improve the patient’s compliance
To produce a targeted drug delivery
To reduce the reactivity of the core in relation to the outside environment
To decrease evaporation rate of the core material.
To convert liquid to solid form & To mask the core taste.
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5. FUNDAMENTAL CONSIDERATION:
Core material Coating material Vehicle
Solid Liquid
Microencapsulation
Polymers
Waxes
Aqueous Nonaqueous
Resins
Proteins
Polysaccharides
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9. RELEASE MECHANISMS
1. Degradation controlled monolithic system
2. Diffusion controlled monolithic system
3. Diffusion controlled reservoir system
4. Erosion
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10. MICROENCAPSULATION TECHNIQUES:
1. Air suspension techniques( Wurster)
2. Coacervation process
3. Spray drying & congealing
4. Pan coating
5. Solvent evaporation
6. Polymerization
7. Extrusion
8. Single & double emulsion techniques
9. Supercritical fluid anti solvent method (SAS)
10. Nozzle vibration technology
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11. Air Suspension Techniques( Wurster)
Microencapsulation by air suspension technique consist
of the dispersing of solid, particulate core materials in a
supporting air stream and the spray coating on the air
suspended particles. Within the coating chamber,
particles are suspended on an upward moving air stream.
The design of the chamber and its operating parameters
effect a recalculating 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.
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12. During each pass through the coating zone, the core
material receives an increment of coating material.
The cyclic process is repeated, perhaps several
hundred times during processing, depending on the
purpose of microencapsulation the coating
thickness desired or whether the core material
particles are thoroughly encapsulated. The
supporting air stream also serves to dry the product
while it is being encapsulated. Drying rates are
directly related to the volume temperature of the
supporting air stream.
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14. Coacervation process
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 the coating usually by thermal, cross linking or
desolvation techniques to form a microcapsule.
In step 2, the deposition of the liquid polymer around the interface
formed between the core material and the liquid vehicle phase. In
many cases physical or chemical changes in the coating polymer
solution can be induced so that phase separation of the polymer
will occur.
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15. Droplets of concentrated polymer solution will form and coalesce to
yield a two phase liquid-liquid system. In cases in which the coating
material is an immiscible polymer of insoluble liquid polymer it may
be added directly. Also monomers can be dissolved in the liquid
vehicle phase and subsequently polymerized at interface.
Equipment required for microencapsulation this method is relatively
simple; it consists mainly of jacketed tank with variable speed
agitator.
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16. COACERVATION / PHASE SEPARATION
Homogeneous Droplets
Polymer Solution
PHASE
SEPARATION
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Polymeric
Membrane
Coacervate
Droplets
MEMBRANE
FORMATION
1.Formation of three immiscible phase
2.Deposition of coating
3.Rigidization of coating.
18. Spray-Drying & spray-congealing
Spray-Drying & spray-congealing :
- Microencapsulation by spray-drying is a low-cost commercial
process which is mostly used for the encapsulation of fragrances,
oils 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.
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19. Spray-congealing
Spray-congealing:
-This technique can be accomplished with spray drying
equipment when the protective coating is applied as a melt.
1- the core material is dispersed in a coating material melt.
2- Coating solidification (and microencapsulation) is
accomplished by spraying the hot mixture into a cool air
stream.
- e.g. microencapsulation of vitamins with digestible
waxes for taste masking.
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21. SPRAY DRYING & CONGEALING ( COOLING)
Spray drying : spray = aqueous solution / Hot air
Spray congealing : spray = hot melt/cold air
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22. PAN COATING
1- Solid particles are mixed with a dry coating
material.
2- The temperature is raised so that the coating
material melts and encloses the core particles, and
then is solidified by cooling.
Or, the coating material can be gradually applied to
core particles tumbling in a vessel rather than being
wholly mixed with the core particles from the start of
encapsulation.
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24. MULTIORIFIC-CENTRIFUGAL PROCESS
The Southwest Research Institute (SWRI)
has developed a mechanical process for
producing microcapsules that utilizes
centrifugal forces to hurl a core material
particle trough an enveloping
microencapsulation membrane thereby
effecting mechanical microencapsulation.
Processing variables include the rotational
speed of the cylinder, the flow rate of the
core and coating materials, the
concentration and viscosity and surface
tension of the core material. The
multiorifice-centrifugal process is capable
for microencapsulating liquids and solids
of varied size ranges, with diverse coating
materials. The encapsulated product can be
supplied as slurry in the hardening media
or s a dry powder. Production rates of 50
to 75 pounds per our have been achieved
with the process.
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25. POLYMERIZATION
A relatively new microencapsulation
method utilizes polymerization techniques
to from protective microcapsule coatings
in situ. The methods involve the reaction
of monomeric units located at the interface
existing between a core material substance
and a continuous phase in which the core
material is dispersed. The continuous or
core material supporting phase is usually a
liquid or gas, and therefore the
polymerization reaction occurs at a liquidliquid,
liquid-gas, solid-liquid, or solid-gas
interface.
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26. Drug
Monomer(s) (e.g. acrylamide, methacrylic acid)
+ Cross-linker (e.g. methylenebisacrylamide)
Alcohol
Preparation of the
Polymerization Mixture
Addition of the alcoholic solution
of the initiator (e.g., AIBN)
Initiation of
Polymerization
8 hrs Reaction time
Monodisoerse Latex
Formation by Polymer
Precipitation
T (reaction) = 60 °C
Nitrogen Atmosphere
RECOVERY OF POLYMERIC
MICROPARTICLES
Monodisperse microgels in the micron or
submicron size range.
Precipitation polymerization starts from
a homogeneous monomer solution in
which the synthesized polymer is
insoluble.
The particle size of the resulting
microspheres depends on the
polymerization conditions, including the
monomer/co monomer composition, the
amount of initiator and the total
monomer concentration.
POLYMERIZATION:
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27. EVALUATION OF MICROCAPSULES
Percentage Yield
The total amount of microcapsules obtained was weighed and
the percentage yield calculated taking into consideration the
weight of the drug and polymer [7].
Percentage yield = Amount of microcapsule obtained /
Theoretical Amount×100
Scanning electron microscopy
Scanning electron photomicrographs of drug loaded ethyl
cellulose microcapsules were taken. A small amount of
microcapsules was spread on gold stub and was placed in the
scanning electron microscopy (SEM) chamber.
The SEM photomicrographs was taken at the
acceleration voltage of 20 KV.
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28. Particle size analysis
For size distribution analysis, different sizes in a
batch were separated by sieving by using a set of
standard sieves. The amounts retained on
different sieves were weighed [5].
Encapsulation efficiency [8]
Encapsulation efficiency was calculated using
the formula:
Encapsulation efficiency = Actual Drug Content /
Theoretical Drug Content ×100
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29. Estimation of Drug Content
Cefotaxime sodium drug content in the microcapsules was
calculated by UV spectrophotometric (Elico SL159 Mumbai
India) method.
The method was validated for linearity, accuracy and
precision. A sample of microcapsules equivalent to 100 mg
was dissolved in 25 ml ethanol and the volume was
adjusted upto 100 ml using phosphate buffer of pH 7.4. The
solution was filtered through Whatman filter paper. Then the
filtrate was assayed for drug content by measuring the
absorbance at 254 nm after suitable dilution [9].
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30. Invitro Drug release Studies
Drug release was studied by using USP type II dissolution test
apparatus (Electrolab TDT 08L) in Phosphate buffer of pH 7.4 (900
ml). The paddle speed at 100 rpm and bath temperature at 37 ± 0.5°c
were maintained through out the experiment.
A sample of microcapsules equivalent to 100 mg of cefotaxime
sodium was
used in each test. Aliquot equal to 5ml of dissolution medium was
withdrawn at specific time interval and replaced with fresh medium to
maintain sink condition. Sample was filtered through Whatman No. 1
filter paper and after suitable dilution with medium; the absorbance
was determined by UV spectrophotometer (Elico SL159) at 254 nm.
All studies were conducted in triplicate (n=3). The release of drug
from marketed sustained release tablet was also studied to compare
with release from microcapsules.
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31. THANKYOU
AS
EKNATH BABU
STUDENT AT ARULMIGU
KALASALINGAM COLLEGE OF
PHARMACY
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