Microencapsulation and Pelletization

Dr. Md. Abdul Mojid Mondol

B.Pharm. (Hons) and M.Pharm. (RU), Ph.D. (South Korea),
Humboldt Postdoctoral Research Fellow (Germany)

Associate Professor

Bangladesh Open University

 Definition of Microencapsulation
 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.
 Microencapsulation is a process by which solids,
liquids or even gases may be enclosed in
microscopic particles by formation of thin coatings of
wall material around the substances.
 Reasons/Purposes of Microencapsulation
1. To mask undesirable taste and odor of drugs to improve patient
compliance. e.g., Ofloxacin, Aminophylline, castor oil
2. To convert sticky materials in a free flowing powder. e.g.
Thiamine, Riboflavine
3. Conversion of liquid to pseudo solid. e.g., Eprazinone.
4. To protect drugs from oxygen, moisture or light. E.g., Vit. A
Palmitate.
5. Reduction of hygroscopicity. e.g., NaCl.
6. Reduction of vaporization of volatile drugs. e.g., Methyl
salicylate, Peppermint oil
7. Prevention of incompatibilities among drugs. e.g., Aspirin and
Chlorpheniramine maleate
 Reasons/Purposes of Microencapsulation
8. For safe handling of the toxic materials.
9. To get targeted release of the drug.
10. To control release of the active components for delayed
(timed) release or long-acting (sustained) release.
11. To increase bioavailability.
12. To produce a targeted drug delivery.
13. To reduce gastric irritation. e.g. Nitrofurantoin,
Indomethacin
 Microparticles
The product obtained by this process of microencapsulation is
called as microparticles, microcapsules, microsphere, coated
granules, pellets..
 Particles having diameter between 3-800 µ are known as micro
particles or microcapsules or microspheres.
 Particles larger than 1000 µ are known as macroparticles .
Fundamental Consideration or Formulation considerations

Generally Micro particles consist of two components

1. Core material
The solid core can be mixture of API and excipients (stabilizers,
diluents, and release-rate retardants or accelerators).
2. Coat or wall or shell material
Inert substances, which coat on core material with desired thickness
are called as coating material.
Composition of coating:
• Inert polymer
• Plasticizer
• Coloring agent
• Release rate enhancers or retardant
 Disadvantages of Microencapsulation:
 In vivo residual solvent in the microcapsules may be
harmful;
 Expensive process
 Requires skill
 Difficult to obtain continuous and uniform film
Microencapsulation
 Coating material
Water soluble resin Water insoluble resin Wax & lipid Enteric resin
Gelatin Ethyl cellulose Paraffin Shellac
Gum arabic Polyethylene Carnauba wax Zein
PVP Polymethacrylate Bees wax Cellulose acetate
CMC Cellulose nitrate Stearic acid phthalate
Methyl cellulose Silicones Stearyl alcohol
Arabinogalactan
Polyvinyl
acrylate
Polyacrylic acid
Ideal properties of coating material
1. Stabilization of core material.
2. Inert toward active ingredients.
3. Controlled release under specific conditions.
4. Film-forming, flexible, tasteless, stable.
5. Non-hygroscopic, no high viscosity, economical.
6. Soluble in an aqueous media or solvent, or melting.
Microencapsulation Techniques
1. Physical methods
1.1 Air-suspension coating
1.2 Coacervation phase separation
1.3 Pan coating
1.4 Spray drying
1.5 Co-extrusion
2. Chemical process
2.1 Solvent Evaporation
2.2. Polymerization
 Air-suspension coating
 In the air suspension coating , the fine solid core materials are suspended by
a vertical current of air and sprayed with the wall material solution.
 After the evaporation of the solvent, a layer of the encapsulating material is
deposited onto the core material.
 The process can be repeated to achieve the desired film thickness.
Coacervation phase separation
 The term originated from the Latin ›acervus‹ ,
meaning “heap”.
 Coacervation involves the separation of a liquid phase
of coating material from a polymeric solution and
wrapping of that phase as a uniform layer around
suspended core particles.
 Coacervation phase separation (continued)
Methods for coacervation phase separation
•Neutralization of oppositely charged polymers
•Temperature Change
•Incompatible Polymer Addition
•Non- solvent addition
•Salt Addition
Pan coating

Spraying
Wetting Recrystallization Coated particle

Particle Film formation

Coating droplets
 Spray Drying and Congealing

+ Solvent
Co-extrusion
Core material

Coating material
Solvent Evaporation
 Polymerization
Interfacial polymerization
In-situ polymerization
Pharmaceutical and biological applications of
microencapsulation
 Sustained Drug Delivery
 Controlled Drug Delivery
 Local Drug Delivery
 Targeted Drug Delivery
 Protects the pheromone from oxidation and light during
storage and release
 Microorganism and enzyme immobilization
 Protection against UV, heat, oxidation, acids, bases
 Improved shelf life due to preventing degradative reactions
 Masking of taste or odours
 Improved processing, texture and less wastage of ingredients.
 Handling liquids as solids
 Enhance visual aspect and marketing concept.
 Pesticides are encapsulated to be released overtime
 Microencapsulation allows mixing of incompatible compounds.
 Probiotics
EVALUATION OF MICROCAPSULES
1. PercentageYield
Percentage yield = Amount of microcapsule obtained /
Theoretical Amount×100

2. Particle size analysis

 Sieving method
 Optical method
3. Estimation of Drug Content
4. In vitro Drug release Studies
• Microcapsules equivalent to 100 mg drug is placed in USP type
dissolution test apparatus containing 900 ml phosphate buffer (pH
7.4) solution at 100 rpm and 37 ± 0.5°c
• Aliquot equal to 5 ml of dissolution medium is withdrawn at
specific time interval and replaced with fresh medium.
• The solution is filtered and diluted with medium; the absorbance
is taken by UV spectrophotometer at 254 nm.
 Pharmaceutical Pelletization

Definition of Pellets
Pellets are small (0.5-2.0 mm) free flowing, spherical particulate,
manufactured by the agglomeration of fine powder or granules.
Pelletization
 Pelletization can be defined as an agglomeration (size-
enlargement) process that converts fine powders or particles of
bulk drugs and excipients into small, free-flowing, more or less
spherical units.
 “Pelletization” involves the manufacture of agglomerates with
a narrow size range, usually with mean size from 0.5 to 1.5
mm, named “pellets”
Advantages of Pellets
 Uniformity of dose
 Improved aesthetic appearance of products
 Excellent flow properties
 Prevention of dust formation
 Low surface area to volume ratio
 Improvement of hardness and friability
 Disperse freely throughout the GIT
 Dose dumping and the incomplete drug release is avoided.
 Increase patient acceptability
 Sustained release form can be formulated
 Greater bioavailability & uniform drug absorption
 Less volume
 Achieve a unique release pattern.
 Improve stability
 Disadvantages of Pellets
• Expensive processing
• Requires highly specialized equipment
• Low drug loading
• Multiple formulation steps
• Higher cost of production
• Need advance technology
• Proportionally higher need for excipients.
• Lack of manufacturing reproducibility and efficacy.
• Large number of process variables.
• Multiple formulation steps.
• Trained/skilled personal needed for manufacturing.
Classification of Pharmaceutical Pelletization Techniques
1. Agitation
It is a pelletization process in which powders are converted to
spherical particles by a continuous rolling or tumbling action.
a. Balling
The finely divided particles of powder converted to spherical shape
by the addition of liquid prior or during the agitation stage by
continuous rolling or tumbling action.
i. Liquid-induced agglomeration
ii. Melt-induced agglomeration
2. Compaction
The pellets of defined shape and size are formed by subjecting the
blend of powder or granules are forced together under pressure.

A. Compression
Pellets are produced by subjecting the material to the mechanical
pressure. In fact pellets produced compression is nothing but small
tablets that are approximately spheroidal in shape.
B. Extrusion-Spheronization
Extrusion spheronization is a multiple process involving a pre-
consolidation stage by extrusion followed by spheronization to
produce uniform size spherical particles, called as spheroids,
pellets, beads, or matrix pelltets depending upon material as
well as process used.
3. Extrusion-Spheronization
Produces pellets with high loading capacity of active
ingredient without producing extensively larger particles and
particles of uniform size distribution with good flow
properties.

Extrusion-Spheronization is a multistep process involving

1. Dry mixing
2. Wet granulation
3. Extrusion
4. Spheronization
5. Drying
6. Sieving (screening)
Types of extruders
1. Screw-fed extruders
2. Gravity-fed extruders
1. Screw-fed extruders
a. Axial feed screw extruders: These have a die plate that is
positioned axially, consist of a feeding zone, c compression
zone, and extrusion zone.

b. Radial feed screw extruders: Transport zone is short, and the

material is extruded radially through screens mounted around
the horizontal axis of the screws
c. Dome feed screw extruder: These have a cone die plate that is positioned axially,
2. Gravity/Roll Feed Extruders
a. Rotary cylinder Extruder
b. Rotary gear Extruder
c. Rotary radial extruder
 3. Piston Feed Extruders
a. Axial Piston Extruder
b. Radial Piston Extruder

A
B
Spheronizer

Cross-hatch Radial pattern

Different steps involved in spheronization process
3. Drug layering
Pelletization by layering involves the deposition of successive
layers of drug entities from solution, suspension or dry powder on
preformed nuclei, which may be crystals or granules of the same
material or inert starter seeds.

Non-pareils (sucrose+starch) have been widely used as initial

Most recently, microcrystalline cellulose (MCC) has been tested
as a substrate for drug layering
A. Suspension/Solution layering
Solution/suspension layering involves the deposition of
successive layers of solutions and/or suspensions of drug
substances and binders on starter seeds, which may be inert
materials or crystals/granules of the same drug.
2. Drug layering
Successive layering of drug entities from solution, suspension or
dry powder on nuclei (crystals or granules of the same material
or inert starter seeds).
B. Powder layering
The successive layers of powder and excipients are added on
starting seeds by the help of binding liquid. The small particles
and nuclei adhere to each other by means of capillary forces
developed in liquid medium. The process continuous till the
desired pellet size is obtained.
4. Globulation/Droplet formation
In globulation, atomization produces solid particles directly
from the liquid phase through evaporation or cooling and
subsequent solidification of hot melts, solution and
suspension.
A. Spray Drying
B. Spray Congealing / Spray Chilling
A. Spray Drying
The drug entities in solution or suspension are sprayed, with or
without excipients, into a hot air stream to generate dry and
highly spherical particles. As the atomized droplets come in
contact with hot air, evaporation of the application medium is
initiated.
A. Spray Congealing / Spray Chilling
A process in which a drug is allowed to melt, disperse, or
dissolve in hot melts of gums, waxes, fatty acids, etc., and is
sprayed into an air chamber where the temperature is below the
melting points of the formulation components, to provide
spherical congealed pellets under appropriate processing
conditions.
Recent advances in Pelletization Techniques
1. Hot-melt Extrusion and Spheronization
It is a solvent free technique finds a great advantage for drugs
that show sign of instability due to residual water during
processing and storage.

Rotating screw
impose mixing and
agitation result in the
de-aggregation of
suspended particles
in the molten
polymer resulting in
the more uniform
dispersion.
 2. Cryopelletization
In this technique,
freeze dried or
lyophilized pellets are
formed by solidifying
the droplets of aqueous
or organic solutions,
suspensions or
emulsions using liquid
nitrogen (-160 C).
The frozen pellets
dried in a freeze
dryer at -160 C.
3. Freeze pelletization
In this technique, a molten-solid carrier/matrix is introduced as
droplets into an inert column of liquid in which the molten solid
is immiscible.
 MUPS (Multiple unit pellet system)
Dosages form prepared from multipellets are
called MUPS.

MUPS forms:
1. Tablet
2. Capsule