microencapsulation

1. MICROENCAPSULATION

2. CONTENTS
 Introduction
 Reasons for Microencapsulation
 Release Mechanisms
 Fundamental Consideration
 Morphology of Microcapsules
 Techniques to Manufacture
 Application
 Advantages/Disadvantages
 References

3. MICROENCAPSULATION
 Microencapsulation is defined as the
application of a thin coating to individual
core materials that have an arbitrary
particle-size range from 5 to 5000 µm
(Nokhodchi and Farid 2002)
 For solids, liquid and gases

4. MICROCAPSULES VS.
MICROSPHERES

5. REASONS FOR
MICROENCAPSULATION
 To make the formulation sustained or
controlled release.
 To mask the taste & odour of bitter drugs
 A mean of separating incompatible
materials
 To protect the drug from environmental
conditions (light, moisture & oxidation)
 For converting liquid into free flowing
powders
 To prevent the gastric irritation of certain
drugs
 Water solubility or dispersability

6. FUNDAMENTAL CONSIDERATIONS
 Nature of the core and coating materials.
 The stability and release characteristics of the coated
materials.
 The microencapsulation method.

8. CORE MATERIAL
 The core material can be in liquid or solid in
nature. The composition of the core material can
be varied as the liquid core can include dispersed
and/or dissolved material.
 The solid core can be single solid substance or
mixture of active constituents, stabilizers,
diluents, excipients and release- rate retardants
or accelerators.

9. COATING MATERIAL
The selection of coating material decides the
physical and chemical properties of the resultant
microcapsules/microspheres. While selecting a
polymer the product requirements should be
taken into consideration are:
- -stabilization
- - reduced volatility
- - release characteristics
- - environmental conditions, etc.

10. CLASSIFICATION OF POLYMERS

11. MORPHOLOGY OF MICROCAPSULES

12. RELEASE MECHANISMS
1)Degradation controlled monolithic system:
Drug releases on degradation of matrix.
2)Diffusion controlled monolithic system:
Drug released by diffusion then degradation of matrix
occurs.
3)Diffusion controlled reservoir system:
Drug from capsule diffuses then rate controlling
membrane erodes.
4)Erosion:
Due to pH and enzymatic hydrolysis.

13. GENERAL METHODS OF
PREPARATION
Determined by some formulation
and technology related factors.
 The particle size requirement.
 The drug or the protein should
not be, adversely affected by the
process
 Reproducibility of the release
profile
 No stability problem.
 No toxic products associated
with the final product
 Nature of polymer
 Drug
 Intended use
 Duration of therapy

15. Microencapsulation Process Nature(Core) S/L Size Range(um)
 Air Suspension
 Coacervation and phase
seperation
 Pan coating
 Spray drying and congealing
 Solvent evaporation
S
S/L
S
S/L
S/L
35-5000
2-5000
600-5000
600
5-5000

16. CLASSIFICATION
Chemical Process Physico-Chemical
Process
Physico-Mechanical
Process
 Interfacial
Polymerization
 In situ
Polymeraization
 Poly condensation
 Solvent
Evaporation
 Coacervation and
phase seperation
 Sol-gel Encapsulation
 Supercritical CO2
assisted
microencapsulation
 Spray drying and
congealing
 Pan coating
 Fluid bed coating
 Extrusion

17.  Solvent evaporation (Emulsification-Evaporation)
Oil-in-water emulsion (o/w)
Multiple emulsions: Water-in-oil-in-water (w/o/w):
Nonaqueous emulsions: Oil -in -oil (o/o)
 Polymerization techniques
Normal polymerization
 Bulk polymerization
 Suspension polymerization
 Emulsion polymerization
Interfacial polymerization
 Phase separation coacervation technique
 Spray drying and spray congealing

18. 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.

19.  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.

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.

23. 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.

25. 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.

27. SOLVENT EVAPORATION
(EMULSIFICATION-
EVAPORATION)
 Fully developed at end of 1970
 Based on the evaporation of the internal phase of an
emulsion by agitation
DEFINITION :
Process of microencapsulation in which deposition of
coating material or polymer around drug or core material
is carried out by the evaporation of volatile solvent in
which polymer is present. Actually creation of
insufficiency of solvent for polymer by evaporation of
solvent results in precipitation of polymer around core
material & formation of microcapsules. Aggitation is
required during this process

28. METHOD OF PREPARATIONS BY
SOLVENT EVAPORATION PROCESS
Two major techniques are used for
microencapsulation by solvent evaporation.
 Single emulsion solvent evaporation technique
(O/W & O/O)
 Oil in water emulsion technique
 Oil in oil emulsion technique
 Multiple emulsion solvent evaporation technique.
(W/O/W)

29. OIL-IN-WATER (O/W) EMULSION
 Water as nonsolvent to the polymer are in
general preferred.
 Extremely economical and negate the recycling of
the external phase
 Suitable for the encapsulation of lipophilic active
principles
 Microencapsulation of hydrophilic active
principles by this process can pose problems

31. MULTIPLE EMULSIONS:
WATER-IN-OIL-IN-WATER
(W/O/W)
 For the efficient encapsulation of water-soluble
active principles
 Organic phase acts as a barrier between the two
aqueous compartments preventing the diffusion
of the medicine toward the external aqueous
phase
 This process proves much more effective when
the water solubility of the medicine is high (>900
mg/ mL) and prevent partioning of drug into
organic phase
 Sometimes viscosity of primary emulsion is
increased to prevent partioning

33. NONAQUEOUS EMULSIONS:
OIL-IN-OIL (O/O)
 Continuous & discontinuous phase are oil
and immiscible with each other
 For drugs having high hydrophilicity and
gives highest yield
 For drugs/polymers that are degraded in
presence of water
 More expensive than aqueous methods
 Difficult to recycle oil phase
 Traces of oil possesses problems

35. INTERFACIAL POLYMERIZATION
Definition; interfacial Polymerization is a
technique in which polymerization of two
monomers, one oil soluble and other water
soluble, takes place and a polymer is
formed at the interface of two immiscible
substances.
This tech is mostly used for the
encapsulation of liquids rather than solids
b/c penetration of monomer to
polymerization zone is much easy from
the liquid state rather than the solid
state.

36. GENERAL METHOD OF
PREPARATION
 The process consists of bringing two reactants at
the interface of the dispersed phase and the
continuous phases in emulsion system
 This is usually accomplished by emulsifying the
liquid containing first reactant (dispersed phase)
into continuous phase, which is initially devoid of
second reactant
 Additional continuous phase containing the
second reactant is then added. The interfacial
polymerization reaction produces a continuous
film of the polymer around the drug.
 Microcapsules can be recovered by spray drying
or filtration

37. Interfacial Polymerization

38. PROCEDURES ADOPTED FOR
INTERFACIAL POLYMERIZATION
 Procedure for water immiscible liquid core
 Procedure for water miscible liquid core
 Procedure for solid core

39. PROCEDURE FOR WATER
IMMISCIBLE LIQUID CORE
When the core material is lipophilic liquid, the
monomer is dissolved in the liquid core. Usually
isocyanate or acid chloride is user as monomer.
Then this solution is disperesed in aqueous phase
(containing 2nd
monomer) this prpduces
poolymerization of monomers at the interface &
results in formation of the capsule wall

40. PROCEDURE FOR WATER MISCIBLE
LIQUID CORE
Aqueous solution of water soluble drug
(dispersed phase) containing monomer is
dispersed in to an organic phase
(continuous phase) which contain the
emulsifier to form W/O emulsion. When
additional oil containing 2nd
monomer is
added to W/O emulsion, polymer
membrane is formed. Then microcapsules
are separated by different techniques

41. PROCEDURE FOR SOLID CORE
Solid cores are encapsulated by vinyl monomers
that polymerizes by free radical reaction.
 Different solvents used
o CCl4
o Chloroform
o Methanol
o Water
 Different monomers used
Polyamines (hexamethylene diamine) polyphenol
(hydroxy phenol propane) polybasic acid halide
(sebacoyl chloride)

42. APPLICATIONS OF INTERFACIAL
POLYMERIZATION
Some important applications are as follows;.
 Enzymes
 Proteins
 Artificial cells
 Pharmaceuticals
 Adsorbants
 Hormones and antibiotics
 Pigments, oily liquids & polyelectrolytes

43. COACERVATION OR PHASE
SEPARATION TECHNOLOGY
Coacervation is derived from Latin word acervus
means aggregation and the prefix co indicates
the preceding union of the colloidal particles.
This term was first used to described the
phenomenon of phase separation in colloidal
system and thus it was defined as

44. A process in which aqueous colloidal solutionA process in which aqueous colloidal solution
separate upon alteration of thermodynamicseparate upon alteration of thermodynamic
condition of state into two liquid phases, one richcondition of state into two liquid phases, one rich
in colloid i.e. the coacervate & the otherin colloid i.e. the coacervate & the other
containing little colloidcontaining little colloid.
Deposition of this coacervate around drug or core
material form the embryonic capsule & then
appropriate gelling of coacervate resulted in
microcapsules.

46. CORE MATERIAL
The core material or drug which can be
encapsulated by coacervation can be solid, liquid,
gas, liquid slurry, suspension or emulsion and
analgesics, antibiotics, antihistamine,
tranquillizers, iron salts and vitamins

47. WALL MATERIAL
 The coating material can be selected from a
variety of natural and synthetic polymers
depending on the core material to be
encapsulated and the desired characteristics.
 The amount of coating material used ranges from
3%-30%of the total weight.
 Both natural and synthetic colloids can be used,
Hydrophobic colloids are used for encapsulating
water soluble drugs whereas Hydrophobic
colloids are used for encapsulating water
insoluble drugs.

48. METHODS EMPLOYED FOR
COACERVATION
Following methods can be used for coacervation &
the choice of method depend upon the polymer
and the set of conditions which are being used;
 Temperature change
 Salt addition
 Nonsolvent addition
 Incompatible polymer addition
 polymer-polymer interaction

49. TEMPERATURE CHANGE
By temp. change, phase separation of dissolved
polymer takes place in the form of immiscible
liquid droplets, if drug is present these droplets
surround the core & form microcapsules.
A system that utilizes ethyl cellulose &
cyclohexane at high temp. is an example of
thermally induced microencapsulation.
Ethylcellulose is soluble in cyclohexane elevated
temp. but insoluble at room temp. first of all
ethylcellulose is dispersed in cyclohexane & then
mixture is heated to boiling point so that a
homogenous polymer solution is formed. Then
core material is added in the solution with
continous stirring & mixture is allowed to cool.

50. This results in phase separation of ethylcellulose &
microencapsulation of core material. Further
cooling of mixture to room temp. causes gelation
& solidification of the coating.

51. SALT ADDITION
Soluble inorganic salts can be added to aqueous
solution of water soluble polymers to cause phase
separation. A gelation-water-sodium sulphate is
an example. In this system, phase
separation/coacervation is induced by adding
dropwise 20% solution of sodium sulphate.

52. NONSOLVENT ADDITION
A liquid that is a nonsolvent for a given polymer or
does not dissolve the given polymer can be added
to a solution of polymer to induce phase
separation. The resulting immiscible liquid
polymer is used for encapsulation of an
immiscible core.
Fro example;
Cellulose acetate+ methyl ethyl ketone --------
solution of polymer--------- addition of drug
(scopolamine) -------addition of isopropyl ether
(nonsolvent for polymer) --------- phase
separation & microencapsulation of suspended
drug occur.

53. INCOMPATIBLE POLYMER
INTERACTION
Methylene blue-ethylcellulose-liquid polybutadiene
is an example of microencapsulation by
incompatible polymer addition.
Ethyl cellulose is dissolved in toluene to form
polymer solution. Then methylene blue is
dispersed in polymer solution. Phase separation
is carried out by adding liquid polybutadiene
which is soluble in toluene but incompatible with
ethyl cellulose. Thus causes demixing of ethyl
cellulose & phase separation occur.

54. POLYMER-POLYMER INTERACTION
Interaction of two oppositely charged
polyelectrolyte can result in the formation of a
complex having such reduced solubility that
phase separation separation occur.
e.g. gelatin & acacia are examples of oppositely
charged polyelectrolyte because gelatin has
positive charge whereas acacia possess a
negative charge. Gelatin-gelatin, gelatin-CMC
are examples of other oppositely chaeged
polyelectrolyte used in microencapsulatio.

55. DESCRIPTION OF COACERVATION
Coacervation method is divided into two main
groups
 Aqueous phase separation
 Simple coacervatio
 Complex coacervation
 Organic phase separation

56. CHARACTERIZATION
 Recovery of formed microspheres
 Hydration of microspheres
 Drug loading
 Encapsulatipon efficiency
 Rheological properties
 Morphology (SEM,TEM)
 FTIR
 XRD
 TGA/DSC
 Drug release
 Drug release kinetics

60. APPLICATIONS OF COACERVATION
 Antibiotics; E.g amoxicillin, clarithromycin
 Anti-inflammatory drugs; diclofenac sodium,
naproxen.
 Bronchodilators; theophylline.
 Sulfa drugs; sulfadiazine, sulfamerizine.
 Diuretics; furosemide, chlorothiazide.
 Urinary antiseptics; nalidixic acid
 Antiepileptic drugs; phenytoin sodium.

61. APPLICATIONS OF COACERVATION
 Antihypertensive; isosorbide mononitrate,
captopril.
 Analgesics; acetyl salicylic acid
 Anticancers; bleomycin & mercaptopurine.
 Tranquilizers; diazepam & oxazepam
 Electrolyte replenisher; sodium chloride &
potassium chloride.
 Vitamins & metal salts; A, B1, B2, B6, B12, C &
D and mineral salts like Zinc sulphate.
 Converting liquids into free flowing powders; Cod
liver oil, benzaldehyde & other citrus essential
oils

62.  Hydration of microspheres
 Drug loading
 Encapsulation efficiency

65. APPLICATION

66. POTENTIAL APPLICATIONS OF
MICROSPHERES
 Taste and odor masking
 Conversion of oils and other liquids to solids for ease of
handling
 Protection of drugs against the environment as
moisture , light ,heat , oxidation etc and vice versa i.e.
prevention of pain of injection
 Delay of volatilization
 Separation of incompatible materials
 Improvement of flow properties of powders
 Safe handling of toxic substances
 Aid in dispersion of water insoluble substances in
aqueous media
 Production of sustained release, controlled release and
targeted medications
 Reducing dose dumping potential compared to large
implantable devices (Burgess and Hickey 2002).

67. REFERENCES
 1-Leon Lachman, Herbert A. Lieberman, Joseph
L. Kanig,“The Theory and Practice of Industrial
Pharmacy”, 3rd edition, pp.420.
 2-JYOTHI SRI.S* , A.SEETHADEVI , K.SURIA
PRABHA , P.MUTHUPRASANNA AND
,P.PAVITRA ,International Journal of Pharma
and Bio Sciences MICROENCAPSULATION: A
REVIEW