1

MICROENCAPSULATION
Definition:
It is the process by which individual particles or droplets of solid or liquid material (the core)
are surrounded or coated with a continuous film of polymeric material (the shell) to produce
capsules in the micrometer to millimeter range, known as microcapsules.
Or
Microencapsulation may be defined as the process of surrounding or enveloping one substance
within another substance on a very small scale, yielding capsules ranging from less than one
micron to several hundred microns in size

Fundamental Considerations:
 Nature of the core and coating materials.
 Stability and release characteristics of the coated materials.
 Microencapsulation methods

Features of Microcapsule:
Microencapsulation is the packaging of small droplets of liquid or particles with a thin film.
Size:
It ranges in size from 1μm to 1mm.
Shape:
The configuration of the core can be a spherical or irregular particle, liquid-phase suspended
solid, solid matrix, dispersed solid and aggregates of solids or liquid forms.
Classification:
Microcapsules can be classified on three basic categories according to their morphology as
follows,
1. Mononuclear
Mononuclear (core-shell) microcapsules contain the shell around the core.
2. Polynuclear
Polynuclear capsules have many cores enclosed within the shell.
3. Matrix types
In matrix encapsulation, the core material is distributed homogeneously into the shell
material.

In addition to these three basic morphologies, microcapsules can also be multiwalled i.e.
mononuclear with multiple shells, or they may form clusters of microcapsules.
Composition:
Microcapsules consist of
 Core material.
 Coat or wall or shell material.
 vehicle
Core materials:
The material to be coated. It may be liquid or solid or gas.
Composition of core material
Liquid core may be dissolved or dispersed material.
Solid core may contain drug, diluent, stabilizers and release rate inducers or inhibitors
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Coating materials:
 Gums; Gum Arabica, Sodium alginate, Carrageenan.
 Carbohydrates; Starch, dextran, sucrose
 Celluloses; Carboxymethylcellulose, methycellulose.
 Lipids; Bees wax, stearic acid, phospholipids.
 Proteins: Gelatin, albumin.

Chemical Classification of Polymers

REASONS FOR ENCAPSULATION:

This technique has been widely used;
1. For masking the organoleptic properties like taste and odor of many drugs and thus
improves patient compliance e.g. Nitrofurantoin for masking the bitter taste.
2. For converting liquid drug in a free flowing powder.
3. For protecting moisture, light and oxygen sensitive drugs such as Nifedipine is protected
from photo instability, vitamin A palmitate is protected from oxidation etc.
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4. For preventing the incompatibility between different drugs

5. The drugs which are volatile in nature may vaporize at room temperature like
peppermint oil can be prevented by microencapsulation.
6. For sustained, delayed or prolonged release of the drug.
7. For targeted drug delivery and to increase the bioavailability of d r u g .
8. Reduction in toxicity and GI irritation e.g., with KCl and ferrous sulphate.
9. For changing the site of absorption of drugs that have high toxicity at lower pH.

Criteria for Microencapsulation:

Preparation of microspheres should satisfy certain criteria:
 Should have ability to incorporate reasonably high concentrations of the drug.
 Should be stable after synthesis with a clinically acceptable shelf life.
 Should have controlled particle size and dispensability in aqueous vehicles for injection.
 Should release active reagent with a good control over a wide time scale.
 Should be biocompatible with a controllable biodegradability.
 Should be susceptible to chemical modification .

Mechanisms and Kinetics of Drug Release:

Major mechanisms of drug release from microcapsules include diffusion, dissolution,
osmosis and erosion.

1. Diffusion
Diffusion is the most common mechanism of drug release (core material) in which the
dissolution fluid penetrates the shell. When the core material comes into contact with the
dissolution fluid it leaks out through the pores. Basically, the release of core material
depends on
 The rate of drug dissolution in the dissolution fluid
 The rate of penetration of dissolution fluid to the microcapsules
 The rate at which the dissolved drug escape from the microcapsule
The kinetics of such drug release follows Higuchi’s equation i.e.
Q = [D/J (2A – ε CS) CS t] ½
Here,
Q is the amount of drug released per unit area of exposed surface in time t
J is the tortuosity of the capillary system in the wall
D is the diffusion coefficient of the solute i n solution
A is the total amount of drug per unit volume
ε is the porosity of the wall of microcapsule
CS is the solubility of drug in permeating dissolution fluid

2. Dissolution:
In this mechanism first polymer coat gets dissolved followed by the release of drug. The release of core
material depends on
 The solubility of polymer in the dissolution fluid
 Thickness of coat

3. Osmosis:
The essential requirement of osmosis is semi permeable membrane and in microcapsule polymer coat
serve the purpose. As the process progresses an osmotic pressure is created between the outside
and inside of membrane of microcapsule which results in release of drug through small pores.

4. Erosion:
Erosion of coat generally occur due to pH or enzymatic hydrolysis and causes drug release with
certain coat materials like bee’s wax, stearyl alcohol and glyceryl monostearate.
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Based on various studies concerning the release characteristics, the following considerations can be
made;
 Drug release rate from microcapsules follow the zero order kinetic.
 Microcapsules of monolithic type have the t1/2 dependant release rate for the first half
of the total drug release and thereafter turn down exponentially.
 Microcapsules of monolithic type have large excess of dissolved drug, the release rate is t1/2
dependent throughout the entire drug release. The path travelled by drug is not constant in
monolithic capsules as the drug at the center travels a large distance than the drug at the
surface. Therefore, the release rate in monolithic capsules generally decreases with time.

METHODS OF PREPARATION:
These depends on
DRUG FACTORS:
 Physical properties
 Chemical properties
 Biological activity
 Nature of drug
 Stability of drug
PRODUCTION REQUIREMENT:
 Entrapment efficiency
 Percentage yield

PHYSICAL METHODS:
 Spray drying
 Spray congealing
 Air suspension
 Fluid bed coating
 Pan coating
 Centrifugal extrusion
 Vibration nozzle
 Multi orifice centrifugation process
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 Spinning disk

1-SPRAY DRYING:
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.
2-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.
3-AIR-SUSPENSION COATING
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.
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.

4-FLUID BED COATING

Fluid bed coating is restricted to encapsulation of solid core materials, including liquids absorbed
into porous solids. Solid particles to be encapsulated are suspended on a jet of air and then covered
by a spray of liquid coating material. The capsules are then moved to an area where their shells
are solidified by cooling or solvent vaporization. The process of suspending, spraying, and
cooling is repeated until the capsules' walls are of the desired thickness.

Different types of fluid-bed coaters include top spray, bottom spray, and tangential spray
(a) Top spray
(b) Bottom spray
(c) Tangential spray.

In the top spray system the coating material is sprayed downwards on to the fluid bed such that
as the solid or porous particles move to the coating region they become encapsulated.
The bottom spray is also known as “Wurster’s coater”. This technique uses a coating chamber
that has a cylindrical nozzle and a perforated bottom plate. The cylindrical nozzle is used for
spraying the coating material. As the particles move upwards through the perforated bottom
plate and pass the nozzle area, they are encapsulated by the coating material.
The tangential spray consists of a rotating disc at the bottom of the coating chamber, with the
same diameter as the chamber. During the process the disc is raised to create a gap between the
edge of the chamber and the disc. The tangential nozzle is placed
Above the rotating disc through which the coating material is released. The particles move
through the gap into the spraying zone and are encapsulated. As they travel a minimum distance
there is a higher yield of encapsulated particles.
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5-SPINNING DISK:

 Suspensions 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 the 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 (usually cooling).
 This technology is rapid, cost-effective, and relatively simple and has high production
efficiencies.

6-PAN COATING:

When coating is liquid?

Coating is applied as a coating solution or atomized spray to the dried solid core particles in the
coating pan.
To remove the coating solvent warm air is supplied to the coated materials while coatings are
applied in the coating pan.
On some cases the solvent is removed by drying in the oven.

When coating is solid?

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.

7-CENTRIFUGAL EXTRUSION:
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As shown in Figure
 The simple extrusion method utnizes a device consisting of two concentric tubes
containing aligned fluid nozzles.
 The liquid material to be coated is extruded through the nozzle of the inner tube into the
coating fluid contained in the outer tube.
 Initially. The fluid extrudes as a rod surrounded by the coating fluid, but the rod
ultimately breaks up into droplets which are then immersed in the coating fluid.
 As the extruded droplets pass through the nozzle orifice of the outer tube.
 The coating fluid forms a surface coat which encases the extruded particle.

 Spherically shaped particles are formed by the surface tension of the liquid.
 By suitable means the formed coat is converted to a more rigid structure. Hardening
baths are usually employed for this purpose.

8-VIBRATIONAL NOZZLE:
It works under the same principle as the extrusion only difference is that an additional
vibrational nozzle is used for encapsulation and flow of fluid is laminar.
Matrix-encapsulation can be done using a laminar flow through a nozzle and an additional
vibration of the nozzle or the liquid.

9-MULTI ORIFICE-CENTRIFUGAL PROCESS:

Microencapsulation by the multi orifice-centrifugal process is the mechanical process in which
the centrifugal force is applied to throw a core material particle through an enveloping
microencapsulation membrane.

The factors affect the Process include the rotational speed of the cylinder, the flow rate of the
coating and core materials and the concentration, viscosity and surface tension of the core
material.
It consists of a cylinder containing three circumferential grooves (coating material inlet)
Core material inlet
Counter rotating disc
Rotating cylinder
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Process:
 Coating material is introduced through the inlet grooves.
 The coating material under the influence of centifugational force imparted by cylinder
rotation flows outward along the immediate groove and form film on orifice.
 The counter rotating disc disperses the core material towards the orifice.
 Core material encounters the coating material membrane at orifice and encapsulation
occurs.

CHEMICAL METHODS:
1-SOLVENT EVAPORATION METHOD

Process
 Step I (Dispersion of Drug in Polymer Solution)
In this process microcapsule coating (polymer) is dissolved in a volatile solvent, which
is immiscible with the liquid manufacturing vehicle phase.Methylene chloride is a
preferred solvent because of its high volatility (boiling point 41C). Mixed solvents can
also be used. The mixtures used so far tend to contain a water-immiscible solvent (e.g.,
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CH2CI2) and a water-miscible solvent (e.g., acetone). The water immiscible solvent is
the predominant component of the mixture.
Once the desired coating polymer is dissolved in the organic solvent, the drug to be
encapsulated is added to this solution. The drug agent may be a solid (crystalline or
amorphous) or a nonvolatile liquid. The added drug may completely dissolve in the
polymer solution or it may be completely insoluble and simply form a dispersion,
suspension, or suspension-emulsion.

 Step II (Emulsification)
To obtain the microcapsule of appropriate size the core and coating material mixture is
dispersed in the liquid manufacturing vehicle phase (water) with agitation.
The drug/polymer/solvent mixture (i.e., the oil phase) is emulsified in water to form an oil-in-
water emulsion.
In order to aid emulsification, a surfactant (PVA) is normally dissolved in the water phase
before the oil-in-water emulsion is formed.
 Step III (Evaporation)
Evaporation is carried out by heating.
 Step IV (Separation)
Once solvent evaporation appears to be complete, the capsules are separated from the
suspending medium by filtration, washed, and dried.

If the core material is dispersed in the polymer solution the polymer shrinks around the core.
And if core material is dissolved in the coating solution matrix type microcapsules are formed.

POLYMERIZATION:

Microencapsulation by polymerization involved reaction of monomeric units located at

interface between a core material substance and continuous phase in which the core material is
dispersed. In polymerization a liquid or gaseous phase is used as continuous or core material
and as a result the polymerization reaction occurs at a liquid-liquid, solid-liquid, Liquid-gas, or
solid-gas interface.

1. Interfacial polymerization (IFP)

In this technique the capsule shell will be formed on the surface of the droplet or particle by
polymerization of the reactive monomers. The substances used are multifunctional monomers.
Generally used monomers include
 Multifunctional isocyanates
 Multifunctional acid chlorides
These will be used either individually or in combination.
Process
The multifunctional monomer (acid chlorides immiscible with water) dissolved in liquid core
material and it will be dispersed in aqueous phase containing dispersing agent. A co reactant
multifunctional amine will be added to the mixture. The polymerization depends on the fact that
acid halides are water insoluble and diamines have partition coefficient toward the water
immiscible organic phase and diffuse towards it and it results in rapid polymerization at
interface and generation of capsule shell takes place.
 A poly urea shell will be formed when isocyanate reacts with amine
 A polynylon or polyamide shell will be formed when acid chloride reacts with amine.

1. In situ polymerization (ISP)

In this process no reactive agents are added to the core material, polymerization occurs
exclusively in the continuous phase. Initially a low molecular weight pre polymer will be
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formed, as time goes on the pre polymer grows in size, it deposits on the surface of the
dispersed core material there by generating a solid capsule shell.

PHYSICOCHEMICAL METHOD:

1- COESERVATION
“A coacervate is a tiny spherical droplet of assorted organic molecules (specifically, lipid
molecules) which is held together by hydrophobic forces from a surrounding liquid.”
Their name derives from the Latin “coacervare”, meaning “to assemble together or cluster.”

PROCESS
The general outline of the processes consists of three steps carried under continuous agitation:
Step 1: Formation of three immiscible chemical phases
The immiscible chemical phases are
(i) A liquid manufacturing vehicle phase
(ii) A core material phase
(iii) 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.
The coating material phase, an immiscible polymer in a liquid state, is formed by utilizing one
of the methods of phase separation coacervation, that is,
 By changing the temperature of the polymer solution
 By adding incompatible polymer to the polymer solution
 By inducing a polymer-polymer interaction

Step 2: Depositing the liquid polymer coating upon the core material
This is accomplished by controlled, physical mixing of the coating material (while liquid) and
the core material in the manufacturing vehicle. Deposition of the liquid polymer coating around
the core material occurs if the polymer is adsorbed at the interface formed between the core
material and the liquid vehicle phase, and this adsorption phenomenon is a prerequisite to
effective coating. The continued deposition of the coating material is promoted by a reduction
in the total free interfacial energy of the system, brought about by the decrease of the coating
material surface area during coalescence of the liquid polymer droplets.
Step 3: Rigidizing the coating
This is usually done by
 Thermal Technique
 Cross linking Technique
 Desolvation Technique, to form a self-sustaining microcapsule.

1-TEMPERATURE CHANGE METHOD:

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Change in temperature causes separation of coating material from the solvent Useful when the
solubility of the material depend on temperature
E.g. Coating mat.: Ethyl cellulose in cyclohexane (EC is insoluble in Cyclohexane at room
temp.)
Core Material: N-Acetyl P-Amino Phenol
The EC is insoluble in cyclohexane at room temperature but is soluble at elevated temperatures.
The mixture is heated to the boiling point to form a homogeneous polymer solution. The finely
divided core material is dispersed in the solution with stirring. Allowing the mixture to cool
with continued stirring, and microencapsulation of the core material occurs.
2- INCOMPATIBLE POLYMER ADDITION:

The polymer which is chemically not compatible will be added to the coating solution

The polymer which is to be added should have

 More affinity towards solvents

 No interaction with the core material.

E.g: Addition of liq. Polybutadiene (Incompatible polymer) to the EC solution in toluene

(Coating sol.).

Core material: Methylene blue HCl.

Dissolves EC in toluene disperse methylene blue with stirring slowly add liq
polybutadiene solidification by addition of hexane filtration and drying of
microcapsules.

3- SALT ADDITION:

 Soluble inorganic salts can be added to aqueous solutions of certain polymers

 Should be soluble in water
 Should precipitate the polymer from the solution.
Eg: Addition of 20% Sod. Sulfate to the gelatin solution.

Core Mat.: Oil soluble vitamin in corn oil.

4- NON-SOLVENT ADDITION

Phase separation can be induced by addition of non-solvent for given polymer. Have
more affinity towards solvent which is used Precipitate the coating polymer

• Eg: Addition of Isopropyl ether to Cellulose acetate butyrate (CAB) dissolved in

Methyl ethyl ketone.

• Core Mat: Methyl Scopolamine HBr

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ENCAPSULATION BY RAPID EXPANSION OF SUPERCRITICAL

FLUIDS

Supercritical fluids are highly compressed gasses.

Properties
 Possess properties of both liquids and gases
 Miscible with common gases such as hydrogen (H2) and nitrogen
Commonly Used Agents
 Supercritical CO2
 Alkanes (C2 to C4)
 Nitrous oxide (N2O)
Supercritical CO2 is widely used for its following properties: -
Properties
 Nontoxic
 Nonflammable
 Readily available
 Highly pure
 Cost-effective
Applications:

It has found applications in encapsulating active ingredients by polymers.

Core Materials Different core materials such as pesticides, pharmaceutical ingredients,
vitamins, and dyes are encapsulated using this method.
Shell Materials A wide variety of shell materials that either dissolve (acrylates, polyethylene
glycol) or do not dissolve (proteins, polysaccharides) in supercritical CO 2 are used for
encapsulating core substances.

Methods:
The most widely used methods are as follows:
 Rapid expansion of supercritical solution (RESS)
 Gas anti-solvent (GAS)
 Particles from gas-saturated solution (PGSS)

I Rapid expansion of supercritical solution (RESS):

In this process, supercritical fluid containing the active ingredient and the shell material are
maintained at high pressure and then released at atmospheric pressure through a small nozzle.
The sudden drop in pressure causes desolvation of the shell material, which is then deposited
around the active ingredient (core) and forms a coating layer.
Disadvantage
 The disadvantage of this process is that both the active ingredient and the shell material
must be very soluble in supercritical fluids.
 The solubility of polymers can be enhanced by using co-solvents and non-solvents.

Example
 Microencapsulation of TiO2 nanoparticles with polymer by RESS using ethanol as a
non-solvent for the polymer shell such as polyethylene glycol (PEG), and polymethyl
methacrylate

A schematic of the microencapsulation process using supercritical CO2

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II GAS ANTI-SOLVENT (GAS) PROCESS:

This process is also called supercritical fluid anti-solvent (SAS). Here, supercritical fluid is
added to a solution of shell material and the active ingredients and maintained at high pressure.
This leads to a volume expansion of the solution that causes super saturation such that
precipitation of the solute occurs. Thus, the solute must be soluble in the liquid solvent, but
should not dissolve in the mixture of solvent and supercritical fluid.

On the other hand, the liquid solvent must be miscible with the supercritical fluid.
Advantage
 It is also possible to produce submicron particles using this method.

Disadvantage
 This process is unsuitable for the encapsulation of water-soluble ingredients as water has
low solubility in supercritical fluids.

III PARTICLES FROM A GAS-SATURATED SOLUTION (PGSS):

This process is carried out by mixing core and shell materials in supercritical fluid at high
pressure. During this process supercritical fluid penetrates the shell material, causing swelling.
When the mixture is heated above the glass transition temperature the polymer liquefies. Upon
releasing the pressure, the shell material is allowed to deposit onto the active ingredient. In this
process, the core and shell materials may not be soluble in the supercritical fluid.

LOADING OF DRUG IN MICROENCAPSULE

Mechanisms For Loading Drug:

Drug can be loaded by

 physical entrapment
 chemical linkage
 surface adsorption

The active components are loaded over the microsphere principally at two points

 During the preparation of microsphere

 After the formation of microsphere by incubating them with the drug or protein.
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Maximum loading can be achieved by incorporating drug during the time of preparation.

Loading during preparation is avoided because during prep loading is effected by

1) Method of preparation.
2) Presence of additives e.g. crosslinking agent, surfactant stabilizer.
3) Heat of polymerization.
4) Agitation intensity.

KINETICS OF DRUG RELEASE:

In some cases, the release rateis zero-order, i.e. the release rate is constant. In this case, the
microcapsules deliver a fixed amount of drug per minute or hour during the period of their
effectiveness. This can occur as long as a solid reservoir or dissolving drug is maintained in the
microcapsule.
A more typical release pattern is first-order in which the rate decreases exponentially with time
until the drug source is exhausted. In this situation, a fixed amount of drug is in solution inside
the microcapsule. The concentration difference between the inside and the outside of the
capsule decreases continually as the drug diffuses.

APPLICATIONS OF MICROENCAPSULATION

Microencapsulation has many applications in pharmaceutical industry especially for the drugs
with poor bioavailability. This method is used in various ways to improve drug delivery to
target sites:

1- Sustained drug delivery:

By encapsulating a drug in a polymer matrix, which limits access of the biological fluid into the
drug until the time of degradation, micro particles maintain the blood level of the drug within a
therapeutic window for a prolonged period. Toxic side effects can be improved by reducing the
frequency of administration. For example novel sustained release microspheres of Glipizide are
quite beneficial for diabetic patient.

2- Mixing of Incompatible Compounds:

Microencapsulation allows mixing of incompatible compounds like for easy addition of oily
ingredients in formulations.
3- Controlled drug delivery:
Using this technique, CR dosage forms can be made through which the drug can be delivered at
a predetermined rate, locally or systemically for a specified period of time. Depot formulation of
short acting peptide have been successfully developed using micro particle technology e.g.
Leuprorelin acetate and triptoreline, both are luteinizing hormone releasing hormone agonists.

4- Improved Shelf Life and Protection Against Environmental Harms:

Microencapsulation of drugs enhances their shelf life by preventing degradative reactions
(dehydration and oxidation). Microencapsulation protects the drugs against environmental effects of
uv-rays, heat, oxidation, acids and bases. e.g.: microencapsulation of vitamin A palmitate and
vitamin K.
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5- Taste and Odour Masking:

Microencapsulation is used to mask the bitter taste of drugs like paracetamol and nitrofurantoin
etc. It also decreases the odour and volatility of certain compounds like carbon tetrachloride.
6- Improved Processing:
Microencapsulation of ingredients results in better control of hygroscopy e.g. of NaCl, enhanced
solubility, flowability and dispersibility, e.g. microencapsulation of non-flowing multicomponent solid
mixture of thiamine, riboflavin, niacin and iron phosphate for easy tableting.
Oils can be encapsulated and tablets can be made thereof.

7- Pulsatile drug delivery:

Pulsatile release of antibiotics can alleviate evolution of the bacterial resistance. In the vaccine
delivery, initial burst followed by delayed release pulsed can mimic an initial and boost injection
respectively. Potential application of this drug delivery system is replacement of therapeutic
agents, gene therapy, and in use of vaccine for treating AIDS, tumors, cancer, and diabetes. The
spheres are engineered to stick tightly to and even penetrate linings in the GIT before
transferring their contents over time into circulatory system

Based on this novel drug delivery technique, Quinidine gluconate CR tablets are used for treating
and preventing abnormal heart rhythm. Glucotrol (Glipizide SR) is an ant diabetic drug used
to control high blood sugar levels.

8- Targeted drug delivery :

 Antitumor microparticles are administered intraarterially and target an organ or
 Body cavity i.e., peritoneum.
 Therapeutic drug delivery of anti cancer drugs. e.g. .doxorubicin and 5-fluorouracil.
c. Markers for analysis/detection. E.g. Detect tumours; infected cells;

Intracellular delivery:

a. Gene delivery e.g. delivery of plasmid DNA

b. Anti-sense therapy e.g. Closing production of certain proteins by delivery of anti-sense
oligonucleotides to bind ribosomal mRNA
c. Intracellular toxins for cancer therapy
d. Ribozyme delivery
e. Drug delivery to cell organelles e.g. mitochondria
f. Vaccine adjuvant i.e. biodegradable polylactic acid and polylactic acid co-glycolic acid
microspheres also act as immune adjuvant by providing a depot formulation of the antigen at the
site of administration. The antigen is thus continuously released to antigen presenting cells.

9- Recombinant Gene Theraphy:

Corrective gene sequence in the form of plasmids is microencapsulated to be incorporated in the
body for the treatment of genetic disorders.

10- Enzyme and Microbes Immobilization:

Enzymes have been encapsulated in cheese to accelerate ripening and flavor development. The
encapsulated enzymes are protected from low pH and high ionic strength in cheese.
Encapsulation of microbes has been used to improve stability of starter culture.
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11- Protection against Environmental Effects:

Microencapsulation protects the drugs against environmental effects of UV rays, heat,
oxidation, acids and bases. E.g: microencapsulation of vitamin A palmitate and vitamin K.

12- Improved Processing, Texture and Less Wastage of Ingredients:

 Control of hygroscopy (NaCl)
 Enhanced flowability and dispersibility
 Microencapsulation of non-flowing multicomponent solid mixture of thiamine,
riboflavin, niacin and iron phosphate for easy tableting.
 Enhanced solubility

13- Microencapsulation of Inslin and Pancreatic Islets:

 For better and prolonged therapeutic effects of insulin.
 For the improvement of compromised pancreatic function.

Advantages of Microencapsulation:
1. Taste and odor masking. e.g.: Fish oils, sulfa drugs.
2. Protection of drugs from environment.
3. Particle size reduction for enhancing solubility of the Sustained or controlled drug delivery e.g.:
KCl, Ibuprofen.
5. Targeted release of encapsulated material.
6. Live cell encapsulation. e.g.: Resealed erythrocytes.
7. Conversion of liquid to free flowing s o l i d s .
8. Delay of volatilization.
10. Separation of incompatible components eg: Excipients, buffers and other d r u g s .
9. Improvement of flow of powder.
10. Safe handling of toxic substances.
11. Aid in dispersion of water insoluble substance in aqueous media.

Disadvantages of Microencapsulation:

1. Possible cross reaction that may occur between the core and wall material selected.
2. Difficult to achieve continuous and uniform film.
3. Shelf life of hygroscopic drug is reduced.
4. More skills and knowledge required to use this advanced and complex technique.
5. Production costs.

Evaluation of Microparticles:

The parameters, methods and techniques used for the evaluation of microcapsules are given in
the following passages.
Note that the terms microspheres and microcapsules are sometimes used interchangeably.

1 Microsphere recovery/yield:
These studies involve determination of the amount of microsphere obtained at the end of
preparation and the amount of polymer and drug consumed in its preparation. It can be
calculated as follow: Percentage Yield = (Practical yield)/ (Theoretical yield) × 100
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Practical yield of microspheres = Amount of encapsulated drug /Amount of added drug

2 Drug Entrapment Efficiency

Determination of Untrapped Drug
The amount of drug present at the surface is measured by digesting the microsphere with saline
(0.9%
w/v) at room temperature, sonicating the solution in an ultrasonic bath for 5 min and
centrifuging it at 3000 rpm for 2 min. The supernatant is filtered through 0.45μm filter and the
drug is quantified by a suitable analytical method.

It is calculated by:

Percentage loading of microsphere = Quantity of free drug present/ Weight of microsphere

Entrapped drug in microsphere:

The residue left over from the extraction of the free and adsorbed drug is mixed with 5ml of
0.1m glacial acetic acid. The sample is centrifuged at 5000rpm for 10 minutes. The supernatant
is filtered through 0.45μm filter and the amount of drug entrapped is quantified by suitable
analytical method.

Percentage of the encapsulated drug = Quantity of drug encapsulated (g) /Quantity of drug
added for encapsulation

3-Surface Morphology:
It provides vital information about the porosity and microstructure of these drug delivery systems.
The most common technique used is scanning electron microscopy (SEM). The sample prepared
for this method should be dehydrated as vacuum field is necessary for image generation in SEM.
Prior to loading the samples are coated with electron dense coating materials such as gold,
palladium or a combination of both to take photomicrograph..

4. Particle Size Analysis:

It is done study to whether the particle size of formulation lies in the optimal range. A wide
variety of methods which employ different physical principles for the determination of size
include:

(A) Manual
a) Optical Microscopy
b) Electron Microscopy

Transmission Electron Microscopy or Scanning Electron Microscopy can be used.

c) Sieving
d) Sedimentation (Andreason Pipette Method)
(B) Automated
a) Particle counters e.g. Optical particle counting and Impaction & inertial techniques
b) Light Scattering techniques e.g Dynamic light scattering or Enhanced laser diffraction
c) Flow cytometry
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d) Field flow fractionation

5. In-vitro Release Studies:

These studies aid in understanding the behavior of these system in terms of drug release and
their efficacy.

Since microsphere is heterogeneous system, the drug release form the polymer takes place through
a diffusion process, in an in vitro environment. As a result, the drug and polymer matrix are phase
separated and form a biphasic system. The release of the drug is determined by the extent of
degradation of polymeric microsphere.
The in vitro release experiment can be performed using the dialysis method. In this method, a
weighed quantity of the microsphere is placed in a dialysis bag, which is immersed in a
larger volume of continuous phase acceptor fluid. The compartment is stirred and the drug which
diffuses out of the microspheres into the continuous phase is periodically sampled and assayed.

Dissolution can also be done to check in vitro release profile of microcapsules. Standard USP
or BP Dissolution apparatus is used.

6. Differential Scanning Calorimetry (DSC) Analysis:

The DSC technique can provide qualitative and quantitative information about the
physicochemical status of the drug in the microcapsule. This involves an endothermic or
exothermic process and the related thermal transitions include melting, recrystallisation,
decomposition, out gassing or a change in the heat capacity of the listed material. DSC is used
to monitor different samples of the same materials to assess their similarities/differences, or
the effects of additives on the thermal properties of the material.

7. In-vivo Tissue Distribution Studies:

Such studies are done to understand the functional characteristics of formulation in a biological
system. To examine the appropriate properties of the formulation in vivo, adult albino mice, rats
or rabbits, etc. of certain specified weight are used.

A calculated dose of the drug is administered to each animal as dispersion in saline with 1% of
tween 80 at predetermined time. Tail vein is used as route of administration and animals are
sacrificed by cervical dislocation. The organs like lungs, liver, kidneys, heart and spleen are
extracted and studied for target action. The tissue samples are stored for 24h at specified
temperatures. Then the concentration of drug localized in each organ is determined
quantitatively using the HPLC method.

In vivo tissue distribution studies in animal models are carried out to prove the hypothesis of
targeting of microsphere/formulation to the organs and compare them with conventional
dosage forms of the drug.

Along with these methods, polymer solubility in the solvents, viscosity of polymer solutions and
density of microcapsules are also checked. To determine the nature of microcapsules as
hydrophilic or hydrophobic, wettability by angle of contact is measured.
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Examples of Microencapsulated Drugs:

Following are some examples of microencapsulated drugs.

Active moiety Characteristic Purpose Final

Property produc
of t Form
Encapsulation
Aspirin Slightly soluble in Taste masking, Tablet or
water sustained capsule
release, reduced
gastric irritation
Paracetamol Slightly soluble in Taste masking Tablet
water
Islet of Langerhans Viable cells Sustained normalization Injection
of
diabetic
Progesterone Slightly soluble in Sustained release Varied
water
Menthol Volatile solution Reduction in Lotion
volatility,
Sustained
Potassium chloride Highly soluble in water Reduction in gastric irritation Capsule
Nifedipine Practically insoluble in Prevention from Dry
Water photo- powder
Instability
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