MICROCAPSULES
SUBMITTED TO-Dr SWATI GUPTA
SUBMITTED BY-ANJ ALI
ENROLLMENT NO.-A10647019004
M.PHARM(PHARMACEUTICS)2nd SEM
MICROCAPSULES
A minute capsule used to contain drugs, dyes, or other
substances and render them temporarily inactive.
.
Generally Micro particles consist of two components
a) Core material
b) Coat or wall or shell material.
Microcapsules: micrometric
reservoir systems
.
Difference Microcapsule and Capsule
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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.(Reduction of volatility)
To convert liquid to solid form & To mask the core taste.
FUNDAMENTAL CONSIDERATION:
Microencapsulation
Core material Coating material Vehicle
Solid Liquid
Polymers Aqueous Non aqueous
Waxes
Resins
Proteins
Polysaccharides
COACERVATION / PHASE SEPARATION
1-FORMATION OF THREE IMMISCIBLE
PHASES
2-DEPOSITION OF COATING
3-RIGIDIZATION OF COATING
Phase Separation Coacervation Technique
Aq/ organic solution polymer
Drug
Drug dispersed or dissolved in the polymer solution
Phase separation induced by different
means Polymer rich globules
Hardening
Microspheres in aq/ organic phase
Separation,
Drying MICROSPHERES
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Step: 1) Three immiscible phases are as:
a) LMVP
b) Core material phase
c) Coating material phase.
Coating material phase formed by utilizing following methods:
A) Temperature change.
B) By addition of incompatible polymer
C) By non-solvent addition
D) By salt addition
E) Polymer-polymer interaction.
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A) Temperature change:-
Core material: N-acetyl p-aminophenol
Polymer:- ethyl cellulose
Solvent: cyclohexane.
EC + Cyclohexane Polymer solution + N-
acetyl p-aminophenol (1:2)
Gelation & solidification of
coating occur
Collected by filteration, decantation &
centrifugal technique.
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B) Addition of incompatiblepolymer:-
Core material: Crystalline methylene blue HCl
Coating material: Ethyl cellulose
Solvent: Toluene
Incompatible polymer: Polybutadiene.
EC + Toluene mixture + methylene blue HCl (1:4)
550C
EC solidify by adding non-solvent hexane,
Collected by titration & drying technique.
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C)By Non-solvent addition:-
Core material: Methyl scopolamine HBr
Coating polymer: Cellulose acetate butyrate
Solvent: Methyl ethyl ketone
Non-solvent: Isopropyl ether.
CA butyrate + Methyl ethyl ketone mixture + methyl
scopolamine
550C
mixture + isopropyl ether
(slowly cool at room temp.,
collected by centrifugation & drying)
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D) By salt addition:-
Core material: oil soluble vitamin
Oil: corn oil
Aq. phase: water
Polymer: gelatin
Salt: sodium sulphate
Salt : emulsion ratio is 4:10.
Oil soluble vitamin + corn oil mixture + water +
sodium sulphate
(oil droplet coated uniformly with gelation)
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E) By polymer-polymer interaction:-
Core material: Methyl salicylate
+ve charge polymer: Gelatin
-ve charge polymer: Gum arabic
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Aq. Gum arabic + Aq. Gelatin mixture + water
4.5 pH, 40-50 0C
polymer interact to causes phase separation
warm
mixture + methyl salicylate
slowly cooled the mixture at 25 0C over 1 hr
rigidization of coating is done by cooling
microencapsule at 10 0C
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Polymerization Techniques
1. Normal polymerization
Monomer
Bioactive
material
Initiator
Polymerization
Polymer block
Mould/
mechanical
fragmentation
Microspheres
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2. Interfacial Polymerization1,4
Monomer/ Aq. Solution of NaOH with
Bioactive Initiator, Surfactant above
material CMC Stabilizer
Dispersion with
vigorous stirring
Micellar solution of polymer in aq. medium
Polymerizat
ion Microspheres
formation
Separation, Washing, Drying
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SPRAY DRYING & CONGEALING ( COOLING):
Spray drying : spray = aqueous solution / Hot air
Spray congealing : spray = hot melt/cold air
FLUIDIZED BED TECHNOLOGY:
SOLVENT EVAPORATIONS:
Active Polymer
Ingredient + Volatile organic solvent Step 1:
Formation of a solution/dispersion of
the drug into an organic polymer
Organic Polymeric Phase
phase.
Addition into an aqueous
phase (+o/w stabilizer)
Step 2:
Formation of Oil-in-Water
Emulsification of the polymer phase
Emulsion into an aqueous phase containing a
suitable stabilizer, thus, forming a o/w
Temperature increase
emulsion.
Solvent Evaporation
Step 3:
Removal of the organic solvent from
Particle Formation by
the dispersed phase by extraction or
Polymer Precipitation
evaporation leading to polymer
precipitation and formation of the
microspheres.
RECOVERY OF POLYMERIC
MICROPARTICLES
Rotational Suspension Separation:
In this process, core material
dispersed in a liquid shell
formation is fed onto a rotating
disk.
A flat disk is shown, but conical
or bowl shaped disks can be used.
Individual core particles coated with a film of shell formation are flung off the
edge of the rotating disk along with droplets of pure coating material.
When the shell formation is solidified,(e.g.. by cooling) microcapsules are
produce.
EXTRUSION:
This method was first patented in 1957.
The process involves forcing a core material dispersed in a molten
carbohydrate mass through a series of dies, into a bath of dehydrating
liquid.
When contact with the liquid is made, the carbohydrate case hardens to
entrap the core material.
The extruded filaments are separated from the liquid bath, dried using an
anti-caking agent such as calcium tripolyphosphate .
This process is particularly useful for heat labile substances such as flavors,
vitamin C and colors.
Multi-orifice Centrifugal Process
SWRI develop a mechanical
process that utilizes centrifugal
forces to hurl, a core material
particle through an enveloping
membrane.
Production rate of 50 to 75
pound/hr have been achieved
with this process.
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Centrifugal extrusion:
NOZZLE VIBRATION TECHNOLOGY :
EVALUATION OF
MICROCAPASULES
1)Morphology
2)Drug content
3)Bulk density
4)Angle of repose
5)Particle size determination
6)Determination of % drug entrapment
7)In vitro dissolution
8)Stability studies.
Partical Size and Shape:
Conventional light microscopy-
Used to determine the shape and outer structure of the
microparticles.
Scanning electron microscopy-
It can be used for the investigation of double walled
systems.
Conflocal fluorescence microscopy-
used for the structure characterization of
multiple walled microspheres.
It allows visualization and characterization of structures
not only on
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the surface, but also inside the particals.
Electron spectroscopy for chemical
analysis:
Used to determine surface chemistry of the microspheres.
ESCA provides a means for the determination of the
atomic
composition of the surface.
The spectra obtained using ECSA can be used to
determine the surface degradation of the biodegradable
microspheres.
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Attenuated total reflectance Fourier Transform- Infrared
Spectroscopy
FT-IR is used to determine the degradation of the polymeric
matrix of the carrier system.
The IR beam passing through the ATR cell reflected many
times through the sample to provide IR spectra mainly of
surface material.
The ATR-FTIR provides information about the surface
composition of the microspheres.
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Density determination :
The density of the microspheres can be
measured by using a multi volume
pychnometer.
The chamber containing the sample is first
pressurized with a gas, preferably helium.
Subsequent expansion of this gas into a
precisely measured volume results in a
pressure drop.
The sample volume and density are then
easily calculated from the two pressure
readings as displayed on the digital indicator
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Isoelectric
point:
The micro electrophoresis is an apparatus used to
measure the electrophoretic mobility of microspheres
from which the isoelectric point can be determined.
By using this data the electrical mobility of the
particle can be determined.
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Angle of
contact
The angle of contact is measured to determine the
wetting property of a micro particulate carrier.
It determines the nature of microspheres in terms of
hydrophilicity or
hydrophobicity.
The angle of contact is measured at the solid/air/water
interface.
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Release Studies
The drugs could be released through the
microspheres by any of the three methods.
Osmotically driven burst mechanism
Pore diffusion mechanism
Erosion or degradation of the polymer
Release studies for microspheres in phosphate saline
buffer of Ph 7.4,are carried out using-
1. Rotating paddle apparatus
2. Dialysis method
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APPLICATIONS :
Application:-
Taste masking e.g. acetaminophen.
Sustain release e.g. aspirin, isosorbide dinitrate.
Conversion of liquid to solid e.g. clofibrate
Odor masking e.g. castor oil, cysteine.
Reducing gastric irritation e.g. phenylbutazone.
Stabilization to oxidation e.g. vitamin
CONCLUSION:
The microencapsulation technique offers a
variety of opportunities such as protection and
masking, reduced dissolution rate, facilitation
of handling, and spatial targeting of the active
ingredient.
This approach facilitates accurate delivery of
small quantities of potent drugs, reduced drug
concentrations at sites other than the target
organ or tissue and protection of labile
compounds before and after administration and
prior to appearance at the site of action.
