MICROENCAPSULATION

Daulat Haleem Khan

MICROENCAPSULATION
Microencapsulation is the process in which small droplets or particles of liquid or solid
material are surrounded or coated by a continuous film of polymeric materials. These are
either reservoir type in which solid or liquid drug core is surouned by a polymeric layer
(known as microcapsules) or solid continuous matrix of polymer loaded with drug
(microspheres). If a solid or a crystalline material is used as the core, the resultant capsule
may be irregularly shaped. However, if the core material is a liquid, simple spherical
capsules, containing a single droplet of encapsulate, may be formed. Microencapsulation
process helps for converting the liquids to solids, changing the colloidal and surface
properties, providing environmental protection and controlling the release characteristics of
different coated materials.
Most microparticle shells are of organic polymers, but waxes and lipids are also used.
Generally the size of the microencapsulated products (microparticles) is considered as larger
than 1micrometer and up to 1000 micrometers in diameter. Commercially available
microparticles contained 10-90% w/w core.

REASONS FOR MICROENCAPSULATION

1. The main reason for microencapsulation is for sustained or prolonged release of the
drug
2. This technique has been widely used for masking the organoleptic properties like taste
and odor of many drugs and thus improves patient compliance e.g. Paracetamol,
nitrofurantoine for masking the bitter taste.
3. By using microencapsulation techniques the liquid drugs can be converted in a free
flowing powder.
4. The drugs can be protected by microencapsulation which is sensitive to moisture light
and oxygen, such as nifedipine is protected from photo instability.
5. Microencapsulation technique is also helpful to prevent the incompability between
drugs.
6. The drugs which are volatile in nature may vaporize at room temperature like
peppermint oil can be prevented by microencapsulation.
7. Reduction in toxicity and GI irritation including with KCl and ferrous sulphate can be
achieved by microencapsulation.
8. Microencapsulation has also been employed to change the site of absorption. This
application has been useful for those drugs which have the toxicity at lower pH.

MATERIALS USED IN MICROENCAPSULATION

CORE MATERIALS
The core material, defined as the specific material to be coated, can be liquid or solid in
nature. The composition of the core material can be varied, as the liquid core can include
dispersed and/or dissolved materials. The solid core can be active constituents, stabilizers,
diluents, excipients, and release-rate retardants or accelerators.
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COATING MATERIALS
The material to be coated on the core material should be capable of forming a film that is
cohesive with the core material, chemically compatible with other materials and nonreactive
with the core material .The coating materials provide the desired coating Properties such as
Strength, flexibility, impermeability, optical properties, and stability.
COATING MATERIAL PROPERTIES
1. Stabilization of core material
2. Inert toward active ingredients
3. Controlled release under specific conditions
4. Film-forming, pliable, tasteless, stable
5. Non-hygroscopic, no high viscosity, economical
6. Soluble in an aqueous media or solvent, or melting
7. The coating can be flexible, hard, thin etc
Table 1: Examples of Coating Material
TYPE OF
MATERIAL
Water soluble resins

Water insoluble resins

Waxes and resins
Enteric resins
Proteins

EXAMPLES
Gelatin, Gum Arabic, Starch, Polyvinylpyrrolidone, Carboxymethylcellulose, Hydroxyethylcellulose, Methylcellulose, Arabinogalactan,
Polyvinyl alcohol, Polyacrylic acid
Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide (Nylon),
Poly (Ethylene-Vinyl acetate), Cellulose nitrate, Silicones,
Poly(lactidecoglycolide)
Paraffin, Carnauba, Spermaceti, Beeswax, Stearic acid, Stearyl
alcohol, Glyceryl stearates
Shellac, Cellulose acetate phthalate, Zein
Collagen, gelatin, casein, fibrinogen, hemoglobin

MICROENCAPSULATION METHODS
1
2
3
4

Air suspension
Coacervation phase separation
Solvent evaporation techniques
Polymerization

MECHANISM OF COAT FORMATION

Following methods are generally used for the drug to be trapped in the form of
microencapsules;
Temperature change: As solvent of the polymer rich phase evaporates by heat treatment
gelation and solidification takes place. A system that utilizes ethylcelluse and cyclohexane at
high temperature is example of thermally induced microencapsulation.
Salt addition: Some salts can be added for the precipitation of the system. a gelatin-watersodium sulfate is example of this method.
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Non-solvent addition: A liquid that does not dissolve the given polymer can be added to a
solution of the polymer to cause phase separation. Addition of isopropyl ether in Cellulose
acetate butyrate-methyl ethyl ketone mixture is example of this method.
Polymer-polymer interaction: the interaction of oppositely charged monomers or
polyelectrolytes can result in the formation of a complex having such reduced solubility that
phase separation occurs. Gelatin gum arabic interaction is example in this case.
AIR SUSPENSION
The air suspension technique involves the dispersion of the core materials in a supporting air
stream and the spray coating on the air suspended particles. The moving air stream suspends
the particles on an upward within the coating chamber. The design of the coating chamber
and its operating parameters should be in such a way that could effect the flow of the particles
through the coating zone of chamber, where a coating material (polymer solution) is applied
to the moving particles. As the moving particles passed through the coating zone repeatedly,
the core material receive more of coating material. The cyclic process is repeated about
several time depending on the coating thickness desired or whether the core material particles
are thoroughly encapsulated. The encapsulated product is dried by passing the stream air.
Drying rates are directly depending to the temperature of the supporting air stream. The
process variables that can affect the process
1) Concentration of the coating material or if in solution form then melting point
2) Solubility, surface area, density, melting point volatility, volatility of core material
3) Application rate of coating material
4) Temperature of air stream
5) The amount of air required to fluidize the core material

COACERVATION PHASE SEPARATION

Three steps formation of three immiscible phases; a liquid manufacturing phase, a core
material phase and a coating material phase
1 Deposition of the liquid polymer coating on the core material
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2

Rigidizing of the coating material

Step-1: The first step of coacervation phase separation involves the formation of three
immiscible chemical phases: a liquid vehicle phase, a coating material phase and a core
material phase. The three phases are formed by dispersing the core material in a solution of
coating polymer, the vehicle phase is used as a solvent for polymer. The coating material
phase consists of a polymer in a liquid phase, is formed by using one of the of phase
separation coacervation method, i.e. .by changing the temperature of the polymer solution, by
adding a solution, or by inducing a polymer- polymer interaction.
Step-2: It involves the deposition of the liquid polymer coating upon the core material. This
is done by controlled mixing of liquid coating material and the core material in the
manufacturing vehicle. The liquid coating polymer deposited on the core material if the
polymer is adsorbed at the interface formed between the core material and liquid phase. The
reduction in the total free interfacial energy of the system help to promote the deposition of
the coating material, brought by the decrease of the coating material surface area during
coalescence of the liquid polymer droplets.
Step-3: In the last step rigidizing of the coating material done by the thermal, cross linking
desolvation techniques, to forms a self supporting microcapsule.

SOLVENT EVAPORATION
Solvent evaporation techniques are performed in a liquid manufacturing vehicle (O/W or O/O
emulsion) which is formed by agitation of two immiscible liquids. In this process
microcapsule coating (polymer) is dissolved in a volatile solvent, which is immiscible with
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the liquid manufacturing vehicle phase. A core material to be microencapsulated is dispersed
in the coating polymer solution. To obtain the microcapsule of appropriate size the core and
coating material mixture is dispersed in the liquid manufacturing vehicle phase with
agitation.

O/W emulsion solvent evaporation technique

This method is used for water insoluble drugs. PLGA and PLA are solublized in some
volatilce solvent systems (Methylene chloride or Chloroform) and drug in some cosolvent.
These two are mixed and emulsified with aqueous phase having emulsifier (Tween, Gelatin,
HPMC). O/W is heat treated for solvent evaporation.

Active
Ingredie
nt

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
Precipitation
Polymer
RECOVERY OF POLYMERIC
MICROPARTICLES

O/O emulsion solvent evaporation technique

The main problem of O/W emulsification process is that this technique cannot be used for
water soluble drug (theophylline, caffeine) because of low entrapment efficacy of such drugs
due to partitioning between two phases. For such drugs O/O system is used. In this technique
polymer and drug are dissolved in polar solvents such as acetonitrile and emulsified with
lipophilic phase (mineral oil) in the presence of oil soluble surfactant such as span. After this
continuous phase is removed after microencapsulation by addition of some solvent that
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solubilizes oil e.g. n-hexane. Cephradine and phenobarbitone are examples of drugs which
are encapsulated by this method.

INTERFACIAL POLYMERIZATION
This technique is one in which two monomers, one oil-soluble and the other water soluble are
employed and a polymer is formed on the surface. This process is conducted by following
methods;
Water immiscible liquid core
When the core material is a water-immiscible liquid, the monomer is dissolved in the liquid
core along with drug. Then this phase is dispersed in aqueous phase containing dispersing
agent and other monomer (co-reactant). Interfacial polymerization takes place among these
monomers to form encapsulated wall.
Water miscible liquid core
An aqueous soluble drug is dispersed in organic phase to form W/O emulsion. Two reactants
are present in two different phases of emulsion which react to form polymer at interface.
Solid core
Solid cores are either encapsulated by vinyl or p-xylene monomers that polymerize by free
radical reaction or polymerization at gas solid interface.
Table 2: Examples of Monomer for microencapsulation by interfacial polymerization
WATER SOLUBLE
MONOMER
1,6-hexamethylene diamine
L-lysine
piperazine
Bis (4-hydroxyphenyl)
propane

OIL SOLUBLE
MONOMER
Sebacoyl chloride
Terephthaloyl chloride
Dichlorodiethyl ether
Sebacoyl chloride

POLYMER
Nylon
Polyterephthalamide lysine
Polyurethane
Polyphenyl ester

VARIOUS FORMULATION FACTORS AFFECTING MICROENCAPSULATION

1.
2.
3.
4.
5.
6.

Polymer (concentration, composition, viscosity, molecular weight, Tc)

Drug (nature, solubility)
Solvent (aqueous, non-aqueous)
Emulsifier (nature, concentration)
Emulsification process (temperature, dispersed phase/continuous phase ratio)
Drug/ polymer ratio

APPLICATION OF MICROENCAPSULATION
1. Paracetamol (taste masking)
2. Aspirin (taste masking, SR preparation)
3. Menthol (reduction in volatility, SR preparation)
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4. Isosorbide dinitrate (SR preparation)
5. Vitamin A (reduction in oxidation)