Microencapsulation

Microencapsulation

Learning
Objectives

At the end of the
session, student will be able to:

• Identify mutiparticulate drug delivery systems

• Differentiate between microparticles and macroparticles

• Differentiate between microspheres and microcapsules

• Enlist the methods for microencapsulation

• Describe air suspension technique for microencapsulation

• Discuss the steps in microencapsulation by coacervation
phase separation technique

• Analyze the differences between spray drying and spray
congealing procedures

• Explain microencapsulation by pan coating method

• Discuss solvent evaporation technique for
microencapsulation

• Outline interfacial polymerization technique

• Classify coating materials used in microencapsulation with
examples

• Outline the applications of microencapsulation techniques
in pharmaceutical and other fields

Introduction
to multiparticulate drug delivery system

The active substance is
present in a number of small independent units

To deliver the required dose,
these unites can be filled into sachets, capsules or compressed into tablet

Microparticles
and Macroparticles

Particles having diameter
between 3 – 800µm are known as microparticles or microcapsules or microspheres

Particles   larger  
than   1000µm   are known as Macroparticles

Classification

Microparticle

1. Microcapsule           

2. Microsphere

Introduction

Microencapsulation is a
process by which very tiny droplets or particles of liquid or solid material
are surrounded or coated with a continuous film of polymeric material

The product obtained by this
process is called as micro particles, microcapsules

Microencapsulation

• In the encapsulate, the active portion is termed the core,
internal phase, or fill

• The encapsulating material is called the shell, coating,
or wall material and may range in both its thickness and number of layers

• Microcapsules can release their contents at controlled
rates at specific conditions

• Shape – ideally spherical; however, their shape is heavily
influenced by the structure of the unencapsulated material

Advantages
of Microencapsulation

To Increase of bioavailability

To alter the drug release

To improve the patient’s
compliance

To produce a targeted drug
delivery

To reduce the reactivity of
the core in relation to the outside environment

To decrease evaporation rate
of the core material.

To convert liquid to solid
form

To mask the core taste

Fundamental
Consideration

Applications
of Microencapsulation

Chemistry

Printing & recording

Carbonless paper,

Adhesives

Pigments and

Fillers Catalysts

Food & feed

Aromas, Probiotics

Unsaturated oil,

Enzyme food processing amino acid for cows

Agriculture

Fungicide – herbicide,

Insect repellent,

Biopesticide

Pigments and fillers

Artificial insemination

Biotechnology & environment

Continuous reactor,

Shear protection,

Reactor oxygenation

Consumer &
diversified

Cosmetics, detergents (enzymes), sanitary (active, aromas)

Carbonless copy paper

Release
Mechanisms of Microencapsulation

1. Degradation controlled monolithic system

2. Diffusion controlled monolithic system

3. Diffusion controlled reservoir system

4. Erosion

Microencapsulation:
Techniques

Air suspension technique

Single & double emulsion

Pan coating

Coacervation

Solvent evaporation

Spray drying and spray Congealing

Polymerization

Extrusion

Air Suspension
Techniques (Wurster)

Wurster Process

Microencapsulation by air suspension technique consist of:

• Dispersing of solid, particulate core materials in a
supporting air stream

• Spray coating the air suspended particles

• Within the coating chamber, particles are suspended on an
upward moving air stream

– The air may be heated or cooled

• The design of the chamber and its operating parameters
effect 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

– The coating, which may be in a molten state or dissolved
in an evaporable solvent

• 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

– 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.

• The coating is atomised through nozzles into the chamber
and deposits as a thin layer on the surface of suspended particles

• The turbulence of the column of air is sufficient to
maintain suspension of the coated particles, allowing them to tumble and
thereby become uniformly coated.

• Upon reaching the top of the air steam, the particles move
into the outer, downward-moving column of air, which returns them to the
fluidised bed with their coating nearly, dried and hardened

• The particles pass through the coating cycle many times
per minute

• With  each  successive 
pass,  the  random 
orientation  of  the 
particles  further ensures their
uniform coating

• The process typically takes from 2 to 12 hours to complete
and achieves exceptionally good coverage, leaving only about 0.2-1.5% of the
particles uncoated

• Air suspension coating can be used with core particles
ranging from 50 to 500 µm

Various variables to
be considered during this process are:

• Volume of the air required to fluidize and support the
core

• Coating material application rate and its concentration

• Amount of coating material required

• Temperatures of the inlets and outlets

• Various parameters of core material such as its melting
point, density, surface area, friability, volatility, crystallinity, flow
ability and solubility.

MICROENCAPSULATION
BY COACERVATION PHASE SEPARATION TECHNIQUE

Coacervation

• Bungenberg and colleagues defined as, partial desolvation
of a homogeneous polymer solution into a polymer-rich phase (coacervate) and
the poor polymer phase (coacervation medium)

• The term originated from the Latin ‘coacervate’, meaning “heap”

• This was the first reported process to be adapted for the
industrial production of microcapsules

Coacervation
– Methods

Simple coacervation –
A desolvation agent is added for phase separation

Complex coacervation –
Involves complexation between two oppositely charged polymers.

Microencapsulation
– Coacervation Technique

STEP 1: Formation
of three immiscible phases

• A liquid manufacturing phase

• A core material phase

• A coating material phase

STEP 2:
Deposition of the liquid polymer coating on the core material

STEP 3:
Rigidizing the coating usually by thermal, cross linking or desolvation techniques
to form a microcapsule

STEP 1: Formation of three immiscible phases

1.   Liquid
manufacturing vehicle

2.   Core material

3.   Coating material

• The core material is dispersed in a solution of the
coating polymer

The three phases are formed by;

Simple coacervation

• Temperature change

• Salt addition

• Nonsolvent addition

• Incompatible polymer addition

Complex coacervation

• Polymer – polymer interaction

1.   Changing temperature of polymer solution

e.g. ethyl cellulose in cyclohexane (N-acetyl P-amino phenol
as core)

2.   Addition of salt

e.g. addition of sodium sulphate solution to gelatine solution
in vitamin encapsulation

3.   Addition of non-solvent

e.g. addition of isopropyl ether to methyl ethyl ketone
solution of cellulose acetate butyrate

4.   Addition of incompatible polymer to the
polymer solution

e.g. addition of polybutadiene to the solution of
ethylcellulose in toluene

5.   Inducing polymer – polymer interaction

e.g. interaction of gum Arabic and gelatin at their
iso-electric point

Step 2: Deposition of liquid polymer upon the core material

• Accomplished by controlled, physical mixing of the coating
material (while liquid) and the core material in the manufacturing vehicle

• Polymer should be adsorbed at the interface formed between
the core and the liquid phase

• Adsorption phenomenon is a pre requisite for effective
coating

Step 3: Rigidization of the coating

Carried out by

   Crosslinking

   Desolvation

   Thermal treatment

 

MICROENCAPSULATION
BY SPRAY DRYING AND SPRAY CONGEALING

Dispersing the core
material in a liquefied coating substance

â

Spraying or
introducing the core coating mixture into suitable environmental condition

â

Rapid solidification
of the coating

Rapid solidification
of the coating

Spray drying – Rapid
evaporation of a solvent in which the coating material is dissolved à Coating solution
dissolved in a solvent

Spray Congealing –
Thermally congealing a molten coating material or by solidifying a dissolved coating
by introducing the coating core material mixture into a nonsolvent à Coating applied as a
melt of waxes, fatty acids, polymers and sugars that are solids at room
temperature but melt at reasonable temperature

5 to 600 microns

Spray dryer

Equipment

Spray drier

Process control
variables

Viscosity, uniformity,
concentration of core and coating material

Feed rate

Method of atomization

Drying rate

MICROENCAPSULATION
BY PAN COATING

Pan Coating

• Microencapsulation of relatively large particles

• Particles larger than 600 microns

• Controlled release beads

• Coating solution atomized on the particles in the coating
pan

• Solvent removed by passing warm air over the coated
particles

• Or by drying in an oven

MICROENCAPSULATION
BY SOLVENT EVAPORATION

Solvent evaporation

Drug Dissolved or dispersed in Solution of polymer in a
volatile solvent à
Dispersed àLiquid
manufacturing vehicle à
Removal of solvent

Process variables → solvent for the polymer, temperature
cycle, agitation rates

MICROENCAPSULATION
BY POLYMERIZATION

Interfacial
Polymerization

• Reaction of monomeric units located at the interface
existing between a core material and
continuous phase                                                                                                                   

Coating
Materials

Water soluble resin

 • Gelatin

• Gum Arabic

• PVP

• CMC

• Methyl cellulose

• Arabinogalactan

• Polyvinyl acrylate

• Polyacrylic acid

Water insoluble resin

 • Ethyl cellulose

• Polyethylene

• Polymethacrylate

• Cellulose nitrate

• Silicones

Wax & lipid

 • Paraffin

• Carnauba wax

• Bees wax

• Stearic acid

• Stearyl alcohol

Enteric resin

Shellac

Zein

Cellulose acetate phthalate

APPLICATIONS
OF MICROENCAPSULATION

Pharmaceutical
Applications

• To improve the flow properties. e.g. Thiamine, Riboflavine

• To enhance the stability. e.g. Vitamins

• To reduce the volatility of materials. e.g. Peppermint
oil, Methyl salicylate

• To avoid incompatibilities. e.g. Aspirin and
Chloramphenicol

• To mask the unpleasant taste and odour. e.g.
Aminophylline, castor oil

• To convert liquids into solids. e.g. Castor oil,
Eprazinone,

• To reduce gastric irritation. e.g. Nitrofurantoin,
Indomethacin

Microencapsulation in
paint industry

• Products such as acrylics, powder coatings, urethane
paints, are key product types currently used with microencapsulation

Thermo-chromic &
photo-chromic apparels/fabrics

• These  fabrics  change 
colour  as  an 
effect  of  change 
in  temperature  in  the
surrounding

• Within the fabric, the microencapsulated colourings are
responsive to thermal changes and light sensitive changes.

Carbonless Paper

• With carbonless paper, the copy is produced by a chemical
reaction between two different coatings (Color producing substance and reacting
substance), which are generally applied to the front and back of a base paper

• This color reaction is caused by pressure (typewriter,
dot-matrix printer, or writing instrument).

Microencapsulated
Scents

• Microcapsules containing fragrances (essential oils) are
applied to paper

• They stay enclosed in the (micro) capsule until pressure
force is applied, under which microcapsule shell ruptures and releases the core
material

• These microcapsules are mostly used in
“scratch-n-sniff” applications e.g. samples perfume inserts in the
newspapers and magazines, promotional advertising campaigns, etc.

Food industry

• Microencapsulated flavors, lipids, and pigments

• Microencapsulation of coffee flavors improves the
protection from light, heat and oxidation when in the dry state, but the core
is released upon contact with water

• Microencapsulated L. acidophilus in cheese

• Microencapsulated probiotics by emulsification in
alginate-chitosan, demonstrating more resistance in simulated gastrointestinal
conditions

• Encapsulated aspartame – improving the protection even at
80°C.

Agriculture

• Controlled Release of Crop Protection Products – a
pesticide product may be most effective at certain humidity or pH levels, or
need to be targeted to the leaves or the roots of the plant

• Sophisticated encapsulation technologies can be designed
with appropriate triggers for maximum efficacy. A pesticide that works on the
leaves of the plant, for example, may be triggered by UV exposure. Another
agrichemical that needs to be applied to the roots in wet conditions may only
be released when rain washes it down into the soil

TOP
COMPANIES IN MICROENCAPSULATION MARKET

Encapsys, LLC

• Provides microencapsulation solutions for paints and
coatings, agriculture, oil and gas, adhesives and sealants, personal and household
care, and paper industries.

Reed Pacific Pty
Limited

   Provides
microencapsulation technology for many different applications such as

– Insect repellent

– Healthcare

– Agriculture

– Consumer products (fabric care and personal care)

– Cosmetic & skin care

– Industrial actives

– Defense & aviation

Ronald T. Dodge
Company

• The company offers services such as microencapsulation,
fragrance delivery, controlled release, encapsulated products, coacervation,
scented coatings, and inks

GAT Microencapsulation
GmbH

• Generic agrochemical products (agro-generics) and biocidal
products such as herbicides, insecticides, acaricides, fungicides, and biocides

Capsulae

• The company offers microencapsulation for human and animal
nutrition, biotechnologies, and chemical industries by using dripping
technology, emulsion- based technology, and coating technology

Microtek
Laboratories, Inc.

• Microencapsulated materials are utilized in agriculture,
pharmaceuticals, foods, cosmetics and fragrances, textiles, paper, paints,
coatings and adhesives, printing applications, and many other industries

Aveka, Inc.

• It offers custom particle processing, manufacturing,
powder process research and development, consulting, prilling, spheroidization,
dry powder coating, and encapsulation services.

TasteTech Ltd.

• The company offers core-shell encapsulation, matrix
encapsulation, spray drying, power stabilization, flavor development, and
contract manufacturing services. The company serves bakery, chewing gum, confectionery,
and sports nutrition markets.

LycoRed Ltd.

• Develops and supplies premixes and microencapsulated
carotenoids, vitamins, minerals, and specialty ingredients for dietary
supplementation, food fortification, coloring, and flavor enhancement applications

Innobio Limited

• The company provides specialty fatty acids, carotenoids,
and branched- chain amino acids

• It offers its product to health concerning markets such as
sport nutrition, weight management, eye health, cognition, vascular care, and
anti-aging

Summary

• Microparticles are a kind of multiparticulate dosage forms

• Microparticles can be in the form of microspheres or
microcapsules

• Microencapsulation if the process of applying polymer
coatings to tiny droplets or particles of liquid or solid material

• Microencasulation has several advantages in biomedical,
pharmaceutical and other fields

• Microencapsulation by air suspension (Wurster) coating
involves application of polymer coat to particles suspended in a stream of air

• Coacervation – Simple and complex

• Steps – Formation of three phases, deposition of coat,
rigidization of coat

• Pan coating – for larger particles

• Solvent evaporation – for organic solvent for polymer

• Spray drying and congealing – by atomizing polymer, core,
solvent mixture in a suitable polymer

• Interfacial polymerization – Reaction of monomeric units
located at the interface existing between a core material and continuous phase

Microencapsulation
can be applied to all sectors of industrial activity

1. Food & Feed

• Flavouring agents & sweeteners

• Enzymes & micro-organisms

• Vitamins, minerals & amino acids

• Plant extracts, aromas, fragrances

• Unsaturated fatty acids            

2. Agriculture &
Environment

• Insecticides and fungicides

• Herbicides and fertilizers

• Repellents and larvicides

• Plant biocontrol & bionutrition

• Water, soil, air treatment

3. Human & Animal
Health

• Vaccination & drug delivery

• Artificial insemination

• Bioartificial organs

• Cell therapy

4. Chemistry

• Adhesives and sealants

• Paints and coatings

• Building & construction materials

• Self-healing materials & PCM

5. Home &
Personal Care

• Cosmetic creams

• Shampoo, toothpaste, soap & shower gels

• Washing powders & washing-up liquids

• Household products

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