microencapsulation for M pharm pharmaceutics, 4th B pharm and 3rd pharm D students

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2. MICROENCAPSULATION
SUHAIL K
Lecturer
Crescent College of Pharmaceutical Sciences
suhailk4@gmail.com
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CONTENTS
Introduction
Fundamental considerations
Methods of preparation
Evaluation
Applications

4. INTRODUCTION
The word “capsule” implies a core and shell structure , and
the term “microcapsule” state that, the membrane enclosed
particle or droplets enclosed in solid matrix.
Microencapsulation is a process by which very tiny droplets 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
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5. ADVANTAGES
 To Increase bioavailability.
 To alter the drug release & separation of reactive core from other
materials.
 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 volatile core material.
 To convert liquid to solid form & To mask the core taste.
 Protects the GIT from irritant effects of the drug.
 Prevents the oxidative degradation of drugs.
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6. DISADVANTAGE
 It’s a costly process.
 Incomplete or discontinues coating
 Required skill .
 It is difficult to get continuous & uniform film.
 Possible cross reaction between the core and coating material.
 Unstable release characteristics of coated products.
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7. FUNDAMENTAL CONSIDRATION
Basic understanding of the general properties of
microcapsules, such as the nature of the coating
materials, the stability and release characteristics of
coated materials, and the microencapsulation method
employed.
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8. Core material Coating material Vehicle
Solid Liquid
Microencapsulation
Polymers
Proteins
Resins
Waxes
polysaccharide
Aqueous Non aqueous
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9. CORE MATERIAL
 The core material is defined as the specific material to be
coated.
 It may be liquid or solid.
 solid core may be dissolved or dispersed material.
 Core material composition provides effectual design and
development of the microencapsule properties.
COMPOSITION OF CORE MATERIAL:
 Drug or active constituent
 Additive like diluents
 Stabilizers
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10. PROPERTIES OF SOME MICROENCAPSULATED CORE MATERIALS.
Core Material Characteristic
Property
Purpose of
Encapsulation
Final Product
Form
Aspirin Slightly water-
soluble solid
Taste-masking; sustained
release; reduced gastric
irritation; separation of
incompatibles
Tablet or
capsule
Vitamin A
Palmitate
Nonvolatile
liquid
Stabilization to oxidation Dry powder
Isosorbide
dinitrate
Water soluble
solid
sustained release Capsule
Acetaminophen Slightly water-
soluble solid
Taste-masking Tablet
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11. COATING MATERIAL
Inert material which coats on core with desired thickness.
IDEAL CHARACTERISTICS
capable of forming a film cohesive with core material.
Chemically compatible with the core material .
Should be stable, non reactive and cheap.
Provide desired coating properties like strength, flexibility and
impermeability.
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12. COMPOSITION OF COATING
 Water soluble resins
Eg: gum arabic, polyvinylpyrrolidone, methyl cellulose, HEC
 Water insoluble resins
Eg: ethyl cellulose, polyethylene
 Waxes and lipids
Eg: paraffin, beeswax
 Enteric resins
Eg: shellac, zein, CAP
 Protiens
 Colorants
 Plasticizers
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13. MECHANISM OF DRUG RELEASE
Include;
1. Diffusion
2. Dissolution
3. Osmosis
4. Erosion
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14. METHODS OF PREPARATION
Preparation of microspheres should satisfy certain criteria:
The ability to incorporate reasonably high concentrations of the
drug.
Stability of the preparation after 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. 14

15. MICROENCAPSULATION METHODS
 Air suspension
 Coacervation- phase separation
 Multiorifice-centrifugal process
 Spray drying and spray congealing
 Pan coating
Solvent evaporation techniques
 Polymerization
 Co extrusion 15

16. 1. AIR SUSPENSION:
Particulate core materials are dispersed in a supporting air stream.
 The coating material is sprayed on the air suspended particles.
 Particle size range 35 – 5000 μm.
 During each pass through the coating zone, the core material
receives an increment of coating material.
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17. The cyclic process is repeated, perhaps several hundred times
during processing, depending on:
the purpose of microencapsulation
the coating thickness desired
Commonly used – gelatin , ethyl cellulose, polyethylene , stearic acid.
The supporting air stream also serves to dry the product while it is
being encapsulated.
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18. WURSTER AIR SUSPENSION APPARATUS
Patented by Wurster in 1950.Salient features of wurster process
are:-
1.Coating chamber
2. Air distribution plate drilled with large diameter holes
in the central portion than those in the periphery.
3. Spray nozzle located at the center of the air-
distribution plate.
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20. Different types of fluid bed coaters include top spray,
bottom spray and tangential spray.
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21. 2. COACERVATION-PHASE SEPERATION
Process consist of 3 steps
1. Formation of three immiscible chemical phase
2. Deposition of the coating
3. Rigidization of coating
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23. 1. Formation of three immiscible chemical phase
a) A liquid manufacturing vehicle phase
b) A core material phase
c) A coating material phase
To form the three phases, the core material is dispersed in a
solution of the coating polymer, the solvent for the polymer being the
liquid manufacturing vehicle phase.
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24. The coating material phase, an immiscible polymer in a liquid
state, is formed by utilizing one of the following phase separation
coacervation method
Temperature change method
Nonsolvent addition
Salt addition
Incompatible polymer addition
Polymer-polymer interaction
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25. 2. Deposition of coating material
 This is accomplished by controlled, physical mixing of the
coating material and core material in the manufacturing
vehicle.
 Deposition of the liquid polymer coating around the core
material occur if the polymer is adsorbed at the interface
formed between the core material and the liquid vehicle phase.
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26. 3. Rigidization of coating
By thermal, cross linking or desolvation technique to form a self
sustaining microsphere.
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27. Temperature change method
Change in temperature cause separation of coating material from
the solvent.
At a particular temperature the polymer concentration the binary
system (polymer+ solvent) become homogeneous.
Add the core materials. The temperature decreases from that point.
Phase separation of the dissolved polymer occurs in the form of
immiscible liquid droplets.
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28. If core material is present in the system, under proper polymer
concentration, temperature, and agitation conditions, the liquid
polymer droplets coalescence around the dispersed core material
particles and forming the embryonic microcapsules.
Coacervtion induced thermally-phase diagram
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29. Disperse 2% w/w EC in cyclohexane.
Heat the mixture to boiling point to get a homogenous polymer solution.
Add core material with stirring.
Allow the mixture to cool.
Filter and dry the resultant microsphere.
Example,
Ethyl cellulose, a water insoluble polymer, is applied to a water
soluble core material, N-acetyl p-amino phenol. Polymer solvent
is cyclohexane
EC is insoluble at room temperature. Soluble in elevated
temperature.
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30. Incompatible polymer addition
It is accomplished by utilizing the incompatibility of dissimilar
polymer existing in a common solvent.
e.g. addition of polybutadiene to the solution of ethylcellulose in
toluene (methylene blue as core material).
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Addition of salt.
Addition of soluble inorganic salts to aqueous
solution of certain water soluble polymers to cause phase
separation.
e.g. addition of sodium sulphate solution to gelatine
solution in vitamin encapsulation.

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Addition of nonsolvent
A liquid that is a non solvent for a given polymer can
be added to a solution of polymer to induce phase separation
e.g. addition of isopropyl ether to methyl ethyl ketone
solution of cellulose acetate butyrate (methylscopolamine
hydrobromide is core).

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Inducing polymer – polymer interaction.
The interaction of oppositely charged
polyelectrolytes can result in the formation of a complex
having such reduced solubility that cause phase separation.
Eg. Gelatin and gum arabic for methyl salicylate core.

37. 2. MULTIORIFICE-CENTRIFUGAL PROCESS
It is a mechanical process for producing microcapsules.
Main coating materials- gelatin , polyvinylpyrrolidone , polyvinyl
alcohol , ethyl cellulose , paraffin …
centrifugal forces are used to hurl a core material particle through
an enveloping microencapsulation membrane.
The multiorifice-centrifugal process is capable for micro
encapsulating liquids and solids of varied size ranges, with
diverse coating materials.
The encapsulated product can be supplied as
- slurry in the hardening media
- dry powder.
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38. Apparatus and working
Equipment used consist of
 A rotting cylinder (1)
 3 grooves within the above cylinder (2,3,4).
grooves 2+4 carry the coating material in moltan or solution
form via tubes(5).
 A counter rotating disc(7) is mounted within the cylinder,
disperse the core material fed through the centrally located
inlet(8).
 The coating material(6) under centrifugal force imparted by the
cylinder rotation, flows outward along the sides of the
immediate groove into the counter sink portion and forms a film
across the orifice.
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39.  A counter rotating disc(7), mounted within the cylinder,
atomizes or disperse the core material.
 The rotating disc flings the particulate core material towards
the orifice.
Core material in the orifice, encounters the coating material
membrane.
 By the impact of centrifugal force, hurls the core material
through the enveloping coating membrane.
 Upon leaving the orifice the microcapsules are hardened,
congealed by different mean.
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40. Processing variables include ;
i. Rotating speed of the cylinder
ii. Flow rate of core, coating material
iii. Concentration and viscosity of coating material
iv. Viscosity and surface tension of core material
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42. 3. PAN COATING
Solid particles greater than 600micron in size
Medicaments are coated on to various spherical substrates such
as nonpareil sugar seeds and then coated with protective layer of
various polymer.
Coating is applied as a solution or atomized spray to the solid
core material in the coating pan.
Coating solvent is removed by passing warm air over the coated
material.
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43. In some cases, final solvent removal is accomplished by drying
in an oven.
Example ; preparation of sustained released pellets of
dextroamphitamine sulphate, which is first coated onto nonpareil
seed and then coated with release rate retarding wax-fat coating.
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ELECTROSTATIC DEPOSITION
The method is suitable for both solids and liquid droplets
 core and coating material are imparted electric charges
by means of high voltage.
Core is charged and placed in coating chamber.
 coating material is charged in solution when it leave the
atomizer devices prior to spray mist.
Both are oppositely charged and coating material gets
deposited on core material.

45. 4. SPRAY DRYING AND SPRAY CONGEALING
These two process are similar, both involves dispersing the core
material in a liquefied or solution of coating substance and spraying or
introducing the core-coating mixture into same environmental
condition where by relatively rapid solidification of coating is effected.
Spray drying :
Core particles are dispersed in a polymer solution and sprayed
into hot air.
The shell material solidifies onto the core material as the solvent
evaporates.
The microcapsules obtained are of polynuclear. 45

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47. Spray congealing:
 The core material is dispersed in a coating material melt.
 Coating solidification and microencapsulation is
accomplished by spraying the hot mixture into a cool air
stream.
Eg : microencapsulation of vitamins with digestible waxes for
taste masking.
By this two we get microsphere in the size range of 5-
600micron, low bulk density.
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48. 5. SOLVENT EVAPORATION.
Coating material is dissolved in a volatile solvent, which is
immiscible with the liquid manufacturing vehicle phase.
Core material to be encapsulated is dissolved or dispersed in the
coating polymer solution.
With agitation, the core coating material mixture is dispersed in the
liquid manufacturing vehicle phase to obtain microcapsule.
The mixture is then heated to evaporate the solvent from the
polymer.
Used to produce microcapsule of liquid and solid core.
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6. RAPID EXPANSION OF SUPERCRITICAL FLUIDS
 Supercritical fluids are highly compressed gasses.
A small change in temperature or pressure cause a large change
in the density of supercritical fluids near the critical point.
Widely used are supercritical carbon dioxide, alkanes and
nitrous oxide.

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Supercritical fluid containing the active ingredients and the
shell material are maintained at high pressure and then released at
atmospheric pressure causes dessolvation of the shell material,
which is then deposited around the active ingredient and forms a
coating layer.
DISADVANTAGES
Ingredients must be soluble in supercritical fluids.

52. 7. POLYMERIZATION
 A relatively new microencapsulation method; utilizes
polymerization techniques to form protective microcapsule.
The method involves 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.
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Interfcial polymerization (IFP)
 The capsule shell will be formed at the surface of the droplets or
particles by polymerization of the reactive monomers by adding co
reactant.
 Generally used monomer include multifunctional isocyanates and
multifunctional acid chlorides.
 Monomers dissolved in liquid core material.
 A co reactant multifunctional amine will be added the mixture.
This results in rapid polymerization at interface.
 A poly urea shell will be formed when isocyanate react with amine.

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Insitu polymerization
Like IFP the shell formation occur because of polymerization of
monomers.
 In this process, no reactive agents are added to the core material.
 Polymerization occurs exclusively in the continuous phase.
 Initially a low mol. wt prepolymer will be formed and then to
polymer shell.

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8. CO EXTRUSION
 A dual fluid stream of liquid shell material and core is pumped
through concentric tube and forms droplets under the influence of
vibration.
 shell is then hardened by cooling or solvent evaporation.
Different types of extrusion nozzles have been developed inorder
to optimize the process.

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9.SPINNING DISC
 suspension of core particles in liquid shell material are
poured into a rotating disc.
Due to the spinning action of the disc the core particles
become coated with shell material.
 the coated particles are then cast from the edge of the disc
by centrifugal force.
After that the shell material is solidified by external means.
Method is rapid, easy, cost effective and effectiveness.

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Microencapsula
tion process
Applicable core
material
Approximate
particle size
(µm)
Air suspension solids 35-5000
Coacervation-
phase
separation
Solids and
liquids
2-5000
Multiorifice
centrifugal
solids 1-5000
Pan coating solids 600-5000
Solvent
evaporation
Solids and
liquids
5-5000
Spray drying and
congealing
Solids and
liquids
600-5000
Microencapsulation process and their applicabilities.

60. 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 .
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 SIEVE ANALYSIS
Separation of the microsphere into various size fraction
can be determined by using a mechanical sieve shaker
 MORPHOLOGY OF MICROSPHERE
The surface morphologies of microspheres are examined
by SEM and ESCA.
 PARTICLE SIZE
Conventional light microscopy and SEM
 BULK DENSITY

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 SOLUBILITY OF POLYMER
Solution turbidity is a strong indication of the solvent power.
Cloud point can be used for the determination of the solubility
of powder.
 INVITRO METHODS
DISSOLUTION STUDY
Standard USP dissolution apparatus have been used for the
study.
Medium used for the study varied from 100-500ml and speed of
rotation from 50-100rpm

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 CAPTURE/ENTRAPMENT EFFICIENCY
It can be determined by allowing washed microsphere to
lyses.
The lysate is then subjected to the determination of active
constituents as per monograph.

64. APPLICATIONS OF MICROENCAPSULATION IN DRUG
THERAPY.
The technology has been used widely in the design of controlled
release and sustained release dosage forms.
To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin
etc.
To reduce gastric and other G.I. tract irritations.
Liquid can be converted to pseudo-solid for easy storage and
handling. Eg; eprazinone.
Protection of core material against external effect.
Targeted drug delivery system.
 prolong the action 64

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REFERENCE
1. Lachman L, Lieberman HA, Kaning JL. The theory and practice of
industrial pharmacy. 3rd ed. Varghese publishers; p. 412-28.
2. Vyas SP, Khar RK. Targeted and controlled drug delivery novel
carrier system. New delhi. p.410-35.
3. Bansode SS, Banarjee SK, Gaikwad DD, Jadhav SL, Thorat RM.
Microencapsulation: a review, vishal institute of pharmaceutical
education and research ale, Pune,1(2)
4. Gupta AK, Dey CK. Microencapsulation for controlled drug
Delivery: a comprehensive review. Sunsari Technical College Journal,
1(1), October 2012.

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