Dr.

Asmaa Abdelaziz Mohamed

PH.D of Pharmaceutics
 Microencapsulation
Microencapsulation is a means of

applying thin uniform coatings to

microparticles of solids dispersion

or droplets of liquids.
 Microcapsules
Microcapsules are small particles that contain an active
agent (core material) surrounded by a shell or coating.
Their diameters generally range from a few microns to a
few millimetres.
Microcapsules can have many different types and
structures:
a) simple droplets of liquid core material surrounded by a
spherical shell (Microcapsules)
b) irregularly-shaped particles containing small particles of
solid core material dispersed in a continuous polymer shell
matrix )microspheres).
Microencapsulated solid Microencapsulated liquid
microspheres
 application of microencapsulation

Four important areas of microencapsulation application are :

1. The stabilization of core materials

2. The control of release or availability of core materials

3. Separation of chemically reactive ingredients within a

tablet or powder mixture.

4. Taste-masking.
 Core Material
 The core material is the material to be coated, which may
be liquid or solid in nature.
 The composition of the core material can be varied:
• The liquid core can include dispersed and/or dissolved
material.
• The solid core can be a mixture of active constituents,
stabilizers, diluents, excipients , and release-rate
retardants or accelerators.
 Some Microencapsulated Core Materials
Core Material Characteristic Purpose of Final
Property Encapsulation Product
Form
Acetaminophen Slightly water- Taste-masking Tablet
Soluble solid
Aspirin Slightly water- Taste-masking; Tablet or
capsule
Isosorbide dinitrate Water soluble solid Sustained release Capsule
Menthol, methyl Volatile solution Reduction of Lotion
Salicylate, camphor volatility; sustained
mixture release
Vitamin A palmitate Nonvolatile liquid Stabilization to Dry powder
prevent oxidation  
Progesterone Slightly water- soluble Sustained release Varied
solid
 Coating Materials
The coating material should:
• Be capable of forming a film that is cohesive with the core
material
• Be chemically compatible and non-reactive with the core
material
• Provide the desired coating properties, such as strength,
flexibility, impermeability, optical properties, and stability.
• Coating material selected from natural and synthetic film-
forming polymers like:
- carboxy methyl cellulose - ethyl cellulose
- cellulose acetate phthalate - poly vinyl alcohol
- gelatin, gelatin- gum arabic - poly hydroxy cellulose
- waxes - chitosan
 Microencapsulation methods

1. Air suspension
2. Coacervation-phase separation
3. Spray drying and spray Congealing
4. Pan coating
Principle Air Suspension

1. The Wurster process consists of the

dispersing of solid particulate core
materials in a supporting air stream
and the spray-coating of the air ­
suspended particles.
2. Within the coating chamber,
particles are suspended on an
upward moving air stream as
indicated in the drawing.
3. The design of the chamber and its
operating parameters provide a
recirculating 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.
4. During each pass through the
coating zone, the core material
receives an increment of coating
material.
5. The cyclic process is repeated several times during
processing, depending on the coating thickness desired.
6. The air stream also serves to dry the product while it is being
encapsulated.
 Pan Coating
In this method, the coating is applied as an
atomized spray to the desired solid core
material in the coating pan. To remove the
coating solvent, a warm air is used in a
process similar to that of tablet coating.

Pan Coating process is used for solid

particles greater than 600 microns in size.
 The coating is applied as a solution, or as
an atomized spray, to the desired solid core
material in the coating pan.
 Warm air is passed over the coated
materials as the coatings are being applied in
the coating pans to remove the coating
solvent.
 Coacervation-Phase Separation
Coating formation during coacervation phase-separation process
consists of three steps carried out under continuous agitation:

Step 1. formation of three immiscible

chemical phases (vehicle ,Core and
liquid coating).

Step 2. Deposition of liquid

coating material.

Step 3. Rigidization of the coating

 Step 1
Formation of three immiscible chemical phases:
A liquid manufacturing vehicle phase, a core material phase,
and a coating material phase.
 is the formation of three immiscible phases which are the
solvent phase, the liquid coating material phase and the
core material phase.
 To form the three phases, the coating polymer solution is
mixed with immiscible solvent to form two immiscible
liquids, then the core material is added to form the third
phase.
 Step 2
Depositing the liquid polymer coating upon the core material.
 Step 2: it consists of depositing(‫ار او‬.‫ستقر‬.‫ا‬
‫رسب‬...‫ )ت‬the liquid coating material on the core
material. Deposition of the liquid polymer
coating around the core material occurs if the
coating polymer is adsorbed at the interface
between the core material and the
immiscible solvent phase, and this
adsorption phenomenon is a prerequisite
(essential) to effective coating.
Step 3

Rigidizing the coating,

it involves rigidizing the coating, usually
by thermal techniques, to form the
microcapsules.
 Ex: Ethyl cellulose (a water insoluble polymer) is applied to
aminophenol powder (core material) by utilizing the
temperature characteristics of the polymer in the cyclohexane
(solvent).
 The Ethyl cellulose is insoluble in cyclohexane at room
temperature, but soluble at elevated temperature.
 The ethyl cellulose and cyclohexane mixture is heated to
form a homogeneous (one phase) solution.
 The aminophenol is dispersed (as insoluble powder) in the
solution with stirring.
 Allowing the mixture to cool with continuous stirring results in
coacervation-phase separation of the ethyl cellulose from
cyclohexane and microencapsulation of the core material.
Allowing the mixture to cool further to room temperature
causes gelation and solidification of the coating.
 The microencapsulated product is collected from by filtration.
 Spray Drying and Spray Congealing
 These methods can be used for both liquid and solid drugs.
 Spray-drying and spray-congealing processes are similar in that
both involve dispersing the core material in a liquid coating
material and spraying the core-coating mixture into certain
environmental condition, whereby rapid solidification of the
coating is achieved.
 The principal difference between the two methods is the means
by which the solidification is achieved.
• Coating solidification in the case of spray drying is achieved by
rapid evaporation of a solvent in which the coating material is
dissolved.
• Coating solidification in spray congealing methods is
accomplished by thermally congealing (cooling)
 In practice, microencapsulation by spray drying is done by
dispersing a core material in a coating solution, in which the
core material is insoluble and then atomizing the mixture into an
 Cont. Spray Drying and Spray Congealing
•The air (hot air) used for vaporization required to remove the
solvent from the coating material
•The equipment used for this purpose is the usual spray dryer.
•Microencapsulation by spray congealing can be accomplished
with spray drying device also. General process variables and
conditions are quite similar to those of spray drying, except that
the core material is dispersed in a coating material melt rather
than the usual coating solution. Coating solidification (and
microencapsulation) is accomplished by spraying the hot
mixture into a cool air.

Ex:Waxes, fatty acids and certain polymers which are solids at

room temperature but melt-able at high temperatures, are
applicable to spray congealing technique.
 Emulsions
‘thermodynamically unstable mixture of two
essentially immiscible liquids
Theories of Emulsification:
When two immiscible liquids are mechanically agitated, both
phases initially tend to form droplets. When the agitation is
stopped, the droplets quickly coalesce(cohere), and the two
liquids separate.

An explanation of this phenomenon is because of cohesive force

between the molecules of each separate liquid exceeds adhesive
force between two liquids. Due to interfacial energy or tension at
boundary between the liquids.
 Therefore, to prevent the coalescence and separation,
emulsifying agents have been used.
 Usually, only one phase persists in droplet form for a prolonged
period of time. This phase is called the internal (disperse or
discontinuous) phase which is finely and uniformly dispersed as
globules throughout the second phase (the continuous phase).
 emulsion contains At least 2 phases:
Disperse or internal phase
or external phase.
 pharmaceutical emulsions range from lotions (low viscosity) to
creams (high viscosity). The particle size of the dispersed phase
commonly ranges from 0.1 to 100 µm
 Types of emulsion

o/w emulsions.
w/o emulsions.
Multiple emulsions (e.g. w/o/w
emulsions).
 1- Oil in water emulsion:
o Aqueous the emulsion is termed oil-in-water (O/W)
o They are non-greasy and are easily removable from the skin
and they are used externally to provide cooling effect
internally to also mask the bitter taste of oil.
o Water soluble drugs are more
quickly released from O/W emulsion.
o O/W emulsion give a positive
conductivity test as water, the external
phase is a good conductor of electricity
 2-Water in oil emulsion
 Water is dispersed as globules in oil (continuous phase) is
termed water-in-oil emulsion (W/O)
 have an occlusive effect by hydrating The stratum corneum
and inhibiting evaporation of sweating secretions
 They are greasy and not water washable
and used externally to prevent evaporation
of the moisture from the surface of skin
.e.g. cold cream
e.g. Oil soluble drugs are more quickly
.released from W/O emulsion
 W/O emulsion is not given a positive
conductivity tests because oil is the
external phase which is a poor conductor
of electricity.
 Multiple emulsions -3
 Multiple emulsions are complex systems.
 They can be considered as emulsions of emulsions.
 Is entirely feasible (can be made) to prepare a multiple
emulsions with the characteristics oil-in-water-in oil
(o/w/w) or of water-in oil-in water (w/o/w) emulsions.
 Such emulsions also can invert however, during
inversion they usually form "simple” emulsions. Thus, a
w/o/w emulsion normally yields an o/w emulsion.
 Microemulsions:
 Microemulsions are systems consisting of water,
oil and surfactant, which constitute a single
optically isotropic ‫متماثل‬and thermodynamically
stable liquid solution.
 Such emulsions appear transparent to the human
eye in daylight.
 In a microemulsions, disperse globules having a
radius below the range of 10 to 75 nm
 Formation of Emulsions
emulsion preparation by the commonly employed
dispersion method requires a sequence of processes
.for breaking up the internal phase into droplets

The requirement in the design of any emulsification

process that the variable physical and chemical
parameters are selected and controlled to favor
.emulsion formation
Physical Parameters
The application of energy as heat, mechanical agitation,ultrasonic
vibration, or electricity is required to reduce the internal phase into
small droplet.
The amount of work input depends on the length of time during which
energy is supplied; thus, timing (scheduling of work input) becomes
another important physical parameter.
1.Heat
-Vaporization is an effective way of breaking almost all the bonds
between the molecules of a liquid. It is possible to prepare
emulsions by passing the vapor of a liquid into an external phase
that contains suitable emulsifying agents This process of
emulsification, called the condensation method but limited to the
preparation of dilute emulsions of materials having low vapor
pressure. The more practical emulsification by dispersion is affected
by temperature changes. The interactions are complex, and it is
almost impossible to predict whether a raise in temperature will
favor emulsification or coalescence.
1. Heat
-Vaporization is an effective way of breaking almost all the bonds between
the molecules of a liquid. It is possible to prepare emulsions by passing
the vapor of a liquid into an external phase that contains suitable
emulsifying agents This process of emulsification, called condensation
method but limited to the preparation of dilute emulsions of materials
having relatively low vapor pressure. The more practical emulsification
by dispersion is affected by heat—or better, changes in temperature.
The interactions are complex, and it is almost impossible to predict
whether a raise in temperature will favor emulsification or coalescence.
-An increase in temperature decreases interfacial tension as well as
viscosity. that emulsification is favoured by an increase in temperature.
however, an increase in temperature raises the kinetic energy of
droplets and thereby facilitates their coalescence.
This type of instability is normally observed when emulsions are stored at
elevated temperatures for long periods of time.
-Changes in temperature alter the distribution of emulsifier between the
two phases and cause emulsifier migration. The distribution of the
emulsifier as a function of temperature cannot be correlated directly
with either emulsion formation or stability
 Phase Inversion Temperature
.The most important influence of temperature on emulsion is inversion
It was observed that w/o emulsions of benzene in water that were-
stabilized with sodium stearate (emulsifier) invert to o/w emulsions upon
.heating and reform w/o emulsions upon cooling
The temperature at which the inversion occurs-
depends on emulsifier concentration and is called
.phase inversion temperature (PIT)
Emulsions formed by a phase inversion technique-
are generally considered quite stable and are
.believed to contain a finely dispersed internal phase
It may be made by the addition of an electrolyte or-
by changing the phase volume ratio or by
.temperature changes
Phase inversion by using the proper emulsifying
agent in adequate concentration, keeping the
concentration of dispersed phase between 30 to 60
percent. And by storing the emulsion in a cool
.place
Timing
During the initial period of agitation required for
,emulsification
droplets are formed; however, as agitation continues, the
Chance for collision between droplets becomes more
frequent,and coalescence can occur. It is generally advisable
to avoid excessive periods of agitation during and after the
.formation of an emulsion
 Formulation of emulsion
The smaller the globules of the disperse phase, the slower will be the rate
of creaming in an emulsion. The size of these globules can also affect the
viscosity of the product, i.e, the smaller the globules, the higher viscosity.
equipment
Mechanical stirrers: by impellers, turbine mixers

Homogenizers: (such as the Silverson mixer-homogenizer) can )2(

also be used to reduce globule size still further
(3) Ultrasonifiers,
(4)Colloid mills:

Colloid mills are also suitable for the preparation of

emulsions.
The extensive shearing of the product they produce
emulsions of very small globule size.
 Cont. formation of emulsion
 In many cases simple blending of the oil and water phases with a
suitable emulgent system sufficient to produce good emulsions.
 small scale by the use of a pestle and mortar or by using a mixer
fitted with an impeller type of agitator, the size and type of which
will depend primarily on the volume and viscosity of the product.
 Fat or oil drugs for oral administration are formulated as o/w
emulsions. In this form, the presence of a flavor in the aqueous
phase will mask any unpleasant taste.
 Emulsions for intravenous administration must be of o/w type,
although intramuscular injections can also be formulated as w/o
products if a water-soluble drug is required for depot therapy
(S.R).
 Emulsions are most widely used for external application. Semisolid
emulsions are such as creams and more fluid-containing
preparations are called either lotions or liniments (liniments are
intended for skin massage).
 Cont. formation of emulsion
 In most cases, the oil phase of an emulsion is the active
agent, and therefore its concentration in the product is
predetermined. Castor oil and cod liver oil are examples
of medicaments which are formulated as emulsions for
oral administration.

 A high viscosity is necessary in order to maintain a

physically stable emulsion. It is important, however, that
these products should be shaken and poured easily from
the container. On the other hand, the main disadvantage
with low-viscosity emulsions is their tendency to cream
easily.
Emulsifing agent choice:
The final choice will depend on the properties and use of the
final product and the other materials required to be present.

The HLB balance

The inclusion of an emulsifying agent(s) is necessary for the
emulsification process during manufacture, and also to ensure
emulsion stability during the shelf-life of the product.
A useful method has been suggested for calculating the
quantities of these emulsifying agents necessary to produce
physically stable emulsion. This is called the hydrophile-lipophile
balance (HLB) method.
Each surfactant has an HLB number representing the relative
proportions of the lipophilic and hydrophilic parts of the molecule.
High numbers (e.g., 20, 30, 33, etc.) indicate a surfactant
exhibiting mainly hydrophilic or polar properties, whereas low
numbers represent lipophilic or non-polar characteristics.
The phase inversion temperature

An o/w emulsion stabilized by non-ionic emulgents will

invert to form a w/o product on heating. This is because,
as the temperature increases, the HLB value of a non-
ionic surfactant will decrease as it becomes more
hydrophobic.
At a temperature at which the emulgent has equal
hydrophilic and hydrophobic tendencies the emulsion will
invert. This temperature is called the phase inversion
temperature.
The stability of an emulsion is related to the phase
inversion temperature of its emulsifying agent.
CLASSIFICATION OF EMULSIFYING AGENTS
There are different classes of emulsifying agents (also called
emulsifiers or emulgents). classified as shown below.
I. Synthetic emulgents
1. Anionic surfactants: in aqueous solutions, these
compounds dissociate to form negatively charged anions that
are responsible for their emulsifying ability. They are widely
used because of their cheapness, but because of their toxicity
are only used for externally applied preparations. Example is
sodium stearate.
2. Cationic surfactants: these materials dissociate to form
positively charged cations in water that provide the emulsifying
properties. The most important group of cationic emulgents
consists of the quaternary ammonium compounds. Like many
anionic emulgents, if used on their own they will produce only
poor emulsions, but if used with non-ionic emulgents (auxiliary)
they will form stable preparations.
Example is Tween.
3. Amphoteric surfactants: this type possesses both positively and
negatively charged groups, depending on the pH of the system. They
are cationic at low pH and anionic at high pH. They are not widely
used as emulsifying agents. Example is lecithin.
II. Natural emulgents
Naturally occurring materials often suffer from two main
disadvantages: they show batch-to-batch variation in composition and
hence in emulsifying properties, and are susceptible to bacterial
growth. For these reasons they are not widely used in manufactured
products requiring a long shelf-life, but rather for extemporaneously
prepared emulsions designed for use within a few days of
manufacture. Example is acacia.
III. Semisynthetic emulgents
In order to reduce the problems associated with natural emulgents,
semisynthetic derivatives are available. Several grades of
methylcellulose and carmellose sodium are available.
Methylcellulose, for example, is used to stabilize Liquid Paraffin Oral
Emulsion.
Other formulation additives
In addition to the emulgents, other additives such as buffers,
preservatives, thickening agents, flavors, colors and sweeteners are
also used.
PHYSICAL STABILITY PROBLEMS
.some cases of physical instability
I.Creaming
It is the separation of an emulsion into two regions, one of which is richer in
the disperse phase than the other. Ex: the creaming of milk, when fat
globules slowly rise to the top of the product. This is not a serious instability
problem that can be reformed by shaking the product (reversible case). It is,
however, undesirable because of the increased risk of coalescence and is
also inelegant and, if the emulsion is not shaken adequately, there is a risk
.of the patient obtaining an incorrect dosage
According to Stokes' law, to slow the rate of creaming the following
:methods can be used
.Production of an emulsion of small droplet size .1
.Increase in the viscosity of the continuous phase .2
Control of disperse phase concentration: It is not easy to stabilize an .3
emulsion containing less than 25% disperse phase, as creaming will readily
occur. A higher disperse phase concentration would result in a hindrance of
.movement of the droplets and reduction in rate of creaming
theoretically possible to include as much as 75% of an internal phase, it is
.found (practically) that at about 60% concentration phase inversion occurs
Flocculation

 Flocculation involves the aggregation of the dispersed

globules into loose clusters within the emulsion.
The individual droplets retain their identities but each
cluster behaves physically as a single unit. This would
increase the rate of creaming.
As flocculation must precede coalescence, any factor
preventing or retarding flocculation would therefore
maintain the stability of the emulsion.
:Coalescence (breaking)
 
o The coalescence (breaking) of oil globules in an o/w emulsion
is resisted by the presence of a mechanically strong adsorbed
layer of emulsifier around each globule. Coalescence results in
separation of the two phases and emulsion failure (irreversible
case).
oCoalescence is usually attributed to the failure of the
emulsifying agent in doing its job. It is necessary therefore, to
ensure that any emulgent system used is not only physically but
also chemically compatible with the active agent and with the
other emulsion ingredients. Ionic emulsifying agents, for
example, are usually incompatible with materials of opposite
charge. Anionic and cationic emulgents are thus mutually
incompatible.
 
 
 how to enhance stability (to prevent creaming
and cracking)?
1-Globule size:
Smaller particles have slower creaming or
sedimentation than larger particles (Stoke’s law).
Stable emulsions require a maximal number of small
sized (1-3 µm) globules and as few as possible
larger (>15 µm) diameter globules.
A homogenizer will efficiently reduce droplet size by
forcing the emulsion through a small aperture to
reduce the size of the globules.
Additionally, reducing droplet size may additionally
increase the viscosity if more than 30% of disperse
phase is present.
.
2-Viscosity of the continuous phase:

Increasing the viscosity of the continuous phase will

reduce the potential for globule creaming and hence
coalescence as this reduces the movement of globules.

How to increase viscosity?

Viscosity enhancing agents, which increase the viscosity
of the continuous phase, may be used in o/w emulsions.
e.g tragacanth, sodium alginate and methylcellulose.
Higher percentages of oil phase (o/w).
Decreasing the particle size of the internal phase.
Higher amounts of solid fats in the oily phase (i.e. high
ratios of solid fat to liquid fats)
2-Using emulsifying agents (hydrocolloids, surfactants and
other) :
Forming interfacial film mechanical barrier which decreases the
potential for coalescence (more important).
Surfactants may reduce the interfacial tension between the two
phases (less important).
Hydrocolloids enhance the viscosity of the medium.
3-Storage temperature:
Extremes of temperature can lead to an emulsion cracking.
When water freezes it expands, so undue pressure is exerted on
dispersed globules and the emulsifying agent film, which may
lead to cracking.
Conversely, an increased temperature decreases the viscosity
of the continuous phase and disrupts the integrity of the
interfacial film. An increasing number of collisions between
droplets will also occur, leading to increased creaming and
cracking.
Application of emulsions
Oral route:
Oral administration of oil-soluble drugs (o/w emulsions).
To enhance palatability of oils when given orally by masking both
taste and oiliness.
Increasing absorption of oils and oil-soluble drugs through
intestinal walls. Ex: griseofulvin in oil in an oil-in-water emulsion.
IM route:
IM depot therapy: Intramuscular injections of some water-soluble
vaccines (w/o emulsions) provide slow release and therefore a
greater antibody response and longer-Lasting immunity.
IV route:
IV (o/w) emulsions for hydrophobic drugs.
Total parenteral nutrition (TPN) makes use of a sterile oil-in water
emulsion to deliver oily nutrients intravenously to patients, using
non-toxic emulsifying agents, such as lecithin.
Topical applications
Transdermal route
Rectal route
 
Identification of emulsion type
Miscibility test:
An emulsion will only mix with a liquid that is miscible with its
continuous phase. Therefore an o/w emulsion is miscible with
water. a w/o emulsion with an oil.
Conductivity measurement:
Systems with an aqueous continuous phase will conduct
electricity, whilst systems with an oily continuous phase will not.
Staining test:
A dry filter paper impregnated with cobalt chloride turns from
blue to pink on exposure to stable o/w emulsions.
Dye test:
If an oil-soluble dye is used, o/w emulsions are paler in colour
than w/o emulsions and vice versa. If examined microscopically.
an o/w emulsion will appear as coloured globules on a
colourless background whilst a w/o emulsion will appear as
colourless globules against a coloured background
Quality control tests for Emulsions 

1.organoleptic properties: such as color, odor

2.Determination of particle size and particle count: 
Determination of changes in the average particle size or the size distribution
of droplets is an important parameter used for the evaluation of emulsions.
It is performed by optical microscopy, sedimentation by
using Andreasen apparatus and Coulter counter apparatus.
2. Determination of viscosity by viscometer or brookfield viscometer
 3. Determination of phase separation: This is another parameter used
for assessing the stability of the formulation. Phase separation may be
observed visually or by measuring the volume of the separated phases.
4.Determination of electrophoretic properties: Determination
of electrophoretic properties like zeta potential is useful for assessing
flocculation since electrical charges on particles influence the rate of
flocculation O/W emulsion having a fine particle size will exhibit low
resistance but if the particle size increase, then it indicates a sign of oil
droplet aggregation and instability.
5- pH: by pH meter
6-assay
7- specific gravity by pycnometer
Thank you