Microencapsulation
Dr. Chirravuri S Phani Kumar, M. Pharm, Ph.D.,
Department of Pharmaceutical Technology.
• Microencapsulation: Is a process of applying relatively thin coatings to small particles
of solids or droplets of liquids and dispersions.
• Microencapsulation involves the coating of particles ranging dimensionally from
several tenths of a micron to 5000 microns in size.
• Microencapsulation provides the means of converting liquids to solids, of altering
colloidal and surface properties, of providing environmental protection, and of
controlling the release characteristics or availability of coated materials.
Limitations:
– No single microencapsulation process is adaptable to all core material candidates or product
applications.
– Difficulties, such as incomplete or discontinuous coating.
– Inadequate stability or shelf-life of sensitive pharmaceuticals.
– Nonreproducible and unstable release characteristics of coated products.
– Economic limitations are often encountered in the attempt to apply a particular microencapsulation
method to a specific task.
– Many times, successful adaptation is, in part, a result of the technical ingenuity of the investigators.
Core Material
The core material, defined as the specific material to be coated, can be liquid or solid in
nature. The liquid core can include dispersed and/or dissolved material, whereas the solid
core can be a mixture of active constituents, stabilizers, diluents, excipients, and release-
rate retardants or accelerators.
Coating Materials
Methodology
•Microencapsulation methods that have been or are being adapted to pharmaceutical use
include air suspension, coacervation-phase separation, spray drying and congealing, pan
coating, and solvent evaporation techniques. Methods not currently applicable to
pharmaceutical preparations are vacuum deposition and polymerization techniques.
•Microencapsulation process
Microencapsulation Applicable core material Approximate particle size
process (μm)
Air suspension Solids 35–5000*
Coacervation-phase Solids and liquids 2–5000*
separation
Multiorifice centrifugal Solids and liquids 1–5000*
Pan coating Solids 600–5000*
Solvent evaporation Solids and liquids 5–5000*
Spray drying and Solids and liquids 600
congealing
1. Air Suspension Coating
• Professor Dale E. Wurster during his tenure at the University
of Wisconsin.
• Processing variables that receive consideration for efficient,
effectiveencapsulation by air suspension techniques include
the following:
1) Density, surface area, melting point, solubility, friability,
volatility, crystallinity, and flowability of the core material.
2) Coating material concentration (or melting point if not a
solution).
3) Coating material application rate.
4) Volume of air required to support and fluidize the core
material.
5) Amount of coating material required.
6) Inlet and outlet operating temperatures.
• The air suspension process offers a wide variety of coating
material candidates for microencapsulation.
• The process has the capability of applying coatings in the form
of solvent solutions, aqueous solutions, emulsions, dispersions,
or hot melts in equipment ranging in capacities from one Wurster air suspension
pound to 990 pounds. encapsulation unit
2. Coacervation-phase Separation
• The National Cash Register (NCR) b) Incompatible Polymer Addition:
Corporation and the patents of B. K. Green Example:The microencapsulation of
et al. methylene blue hydrochloride with
• The general outline of the processes ethylcellulose.
consists of three steps carried out under Ethylcellulose is dissolved in toluene to
continuous agitation . yield a polymer concentration of 2% by
(1) formation of three immiscible weight. Crystalline methylene blue
chemical phases. hydrochloride, being essentially
(2) deposition of the coating. insoluble in toluene. The addition of
(3) rigidization of the coating. polybutadiene cause pase separation &
the ethylcellulose coating is solidified by
a) Temperature Change: adding a nonsolvent for the coating
• Example: polymer such as hexane.
Ethylcellulose, a water- insoluble
polymer, is applied to a water-soluble
core material, N-acetyl p- aminophenol,
by utilizing the temperature-solubility
characteristics of the polymer in the
hydrocarbon solvent cyclohexane.
c) Nonsolvent Addition: d) Salt Addition: Soluble inorganic salts
A 5%, weight to volume, methyl ethyl can be added to aqueous solutions of
ketone solution of cellulose acetate certain water- soluble polymers to cause
butyrate is prepared, and in it, phase separation.
micronized methylscopolamine Example:
hydrobromide is dispersed with stirring. An oil-soluble vitamin is dissolved
A core-material to coating-material ratio in corn oil and is emulsified to the
(methylscopolamine hydrobromide to desired drop size in a 10% solution
cellulose acetate butyrate) of about 2:1 is of high-quality pigskin gelatin
used. The resulting mixture is heated to having an isoelectric point at about
55°C, and isopropyl ether, a nonsolvent pH 8.9. Twenty parts oil to 100 parts
for the coating polymer, is added slowly water, by weight, are used for the
to effect phase-separation/coacervation preparation of the oil/water
and microencapsulation of the suspended emulsion. The emulsification
core material. The system is slowly process is conducted at 50°C, well
cooled to room temperature, and the above the gelation temperature of
microencapsulatesd particles are the gelatin. With the temperature of
separated by centrifugation, washed with the emulsion maintained at 50°C,
isopropyl ether, and dried in vacuum. phase- separation/coacervation is
induced by slowly adding a 20%
solution of sodium sulfate.
e. Polymer-polymer Interaction:
Gelatin and gum arabic are typical
polyelectrolytes that can be caused to
interact causes formation of
microcapsules of the drug methyl
salicylate .
Summary of examples for phase-
separation/coacervation techniques
Flow diagram of a typical
phase-separation/coacervation
process
3. Multiorifice-centrifugal Process
The apparatus, illustrated cross-sectionally in Figure depicts a
rotating cylinder, 1, a major and essential portion of the device.
Located within the cylinder are three circumferential grooves, 2,
3, and 4. Countersunk in the intermediate groove, 3, are a plurality
of orifices spaces closely and circumferentially around the
cylinder. The upper and lower grooves, also located
circumferentially around the cylinder, carry the coating material
in molten or solution form, via tubes, 5, to the respective grooves.
The ridges of the coating material grooves, 2 and 4, serve as a
weir over which the coating material overflows when the volume
of the upper and lower grooves is exceeded by the volume of
material pumped into the system. The coating material, 6, under
centrifugal force imparted by the cylinder rotation, flows outward
along the side of the immediate groove into the countersunk
portion and forms a film across the orifice. A counter rotating
disc, 7, mounted within the cylinder, atomizes or disperses the
core material fed through the centrally located inlet, 8. The
rotating disc flings the particulate core material (liquid droplets or
solid particles) toward the orifices. The core material arrives at the
orifices and encounters the coating material membrane. The
impact and centrifugal force, generated by the rotating cylinder,
hurls the core material through the enveloping coating membrane,
9, which is immediately regenerated by the continually
overflowing coating material.
4. Pan Coating
5. Spray Drying and Spray Congealing
•Spray-drying and spray-congealing processes are similar in that both involve
dispersing the core material in a liquefied coating substance and spraying or
introducing the core-coating mixture into some environmental condition, whereby
relatively rapid solidification (and formation) of the coating is affected.
6. Solvent Evaporation
A core material to be microencapsulated is dissolved or dispersed in the coating
polymer solution. With agitation, the core coating material mixture is dispersed in the
liquid manufacturing vehicle phase to obtain the appropriate size microcapsule. The
mixture is then heated (if necessary) to evaporate the solvent for the polymer.
7. Polymerization
The methods involve the reaction of monomeric units located at the interface existing
between a core material substance and a continuous phase in which the core material
is dispersed. The continuous or core material supporting phase is usually a liquid or
gas, and therefore the polymerization reaction occurs at a liquid-liquid, liquid-gas,
solid-liquid, or solid-gas interface.
Drug Loading
Imbibing
Bonding
Mechanism of Drug Release
1. Diffusion drug delivery.
2. Hydrolysis activated drug delivery- Biodegradable Polymers.
3. Enzyme-Activated drug delivery- Protease activated biodegradable polymers.
Major class of microspheres
1. Chitosan Microspheres
2. Floatinng Microspheres
Characterization of Microspheres
1. Micomeritics
a. Shape & Topography- SEM, TEM/ Optical Microscopy.
b. Size & Size distribution- Laser Diffraction Particle Size Analysis (LDPSA).
c. Surface charge- Zeta potential.
d. Surface & internal structure- Confocal Laser Scanning Microscopy (CLSM).
d. Hallow structure of microballoons- Particle density(Photographic counting method & Liquid displacement
method), Porosity, Pore size distribution(Hg displacement method)
2. Drug entrapment & Content:
a. Drug entrapment- DSC
b. Drug content- UV/ HPLC
3. In vitro Degradation:
4. In vitro Drug Release:
