microencapsulation

1
MICROENCAPSULATION
SHUBHRAJIT MANTRY
Asst.Prof . kottam institute of pharmacy, A.P
2
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.
• Particles having diameter between 3 - 800µm are
  known as micro particles or
• microcapsules or microspheres.
• Particles larger than 1000µm are known as Macro
  particles .

3
CLASSIFICATION OF MICROPARTICLE
Generally Micro particles consist of two
components a) Core
material b) Coat
or wall or shell material.
1.Microcapsules The active agent forms a core
surrounded by an inert diffusion
barrier. 2.Microspheres The active agent is
dispersed or dissolved in an inert polymer.
4
(No Transcript)
5
ADVANTAGES

• To Increase of bioavailability
• To alter the drug release
• To improve the patients 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.

6
FUNDAMENTAL CONSIDERATION
Microencapsulation
Core material Coating material
Vehicle
Solid
Liquid
Polymers
Aqueous
Nonaqueous
Waxes
Resins
Proteins Polysaccharides
7
APPLICATION OF MICROENCAPSULATION TECHNIQUES
8
Microencapsulation Applications
Medicine Pharmacy vetinary Control release,
Taste masking Vectorisation Artificial
organs single dose treatment
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)
9
MICROENCAPSULATION TECHNIQUES
10
MICROENCAPSULATION TECHNIQUES

1. Air suspension techniques( Wurster)
2. Coacervation process
3. Spray drying congealing
4. Pan coating
5. Solvent evaporation
6. Polymerization
7. Extrusion
8. Single double emulsion techniques
9. Supercritical fluid anti solvent method (SAS)
10. Nozzle vibration technology

11
Air Suspension Techniques( Wurster)
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. The
design of the chamber and its operating
parameters effect a recalculating 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.
12
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.
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.
13
Air suspension techniques (WURSTER PROCESS)
14
Coacervation process

• Formation of three immiscible phases a liquid
  manufacturing
• phase, a core material phase and a coating
  material phase.
• Deposition of the liquid polymer coating on the
  core material.
• Rigidizing the coating usually by thermal, cross
  linking or desolvation techniques to form a
  microcapsule.
• In step 2, the deposition of the liquid polymer
  around the interface formed between the core
  material and the liquid vehicle phase. In many
  cases physical or chemical changes in the coating
  polymer solution can be induced so that phase
  separation of the polymer will occur.

15
Droplets of concentrated polymer solution will
form and coalesce to yield a two phase
liquid-liquid system. In cases in which the
coating material is an immiscible polymer of
insoluble liquid polymer it may be added
directly. Also monomers can be dissolved in the
liquid vehicle phase and subsequently polymerized
at interface. Equipment required for
microencapsulation this method is relatively
simple it consists mainly of jacketed tank with
variable speed agitator.
16
COACERVATION / PHASE SEPARATION
1.Formation of three immiscible
phase 2.Deposition of coating 3.Rigidization of
coating.
17
COMPLEX COACERVATION
18
Spray-Drying spray-congealing
Spray-Drying spray-congealing -
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.
19
Spray-congealing

• 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.

20
Spray-Drying
21
SPRAY DRYING CONGEALING ( COOLING)
Spray drying spray aqueous solution / Hot air
Spray congealing spray hot melt/cold air
22
PAN COATING
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.
Or, the coating material can be gradually applied
to core particles tumbling in a vessel rather
than being wholly mixed with the core particles
from the start of encapsulation.
23
(No Transcript)
24
MULTIORIFIC-CENTRIFUGAL PROCESS
The Southwest Research Institute (SWRI) has
developed a mechanical process for producing
microcapsules that utilizes centrifugal forces to
hurl a core material particle trough an
enveloping microencapsulation membrane
thereby effecting mechanical microencapsulation. P
rocessing variables include the rotational speed
of the cylinder, the flow rate of the core and
coating materials, the concentration and
viscosity and surface tension of the core
material. The multiorifice-centrifugal process is
capable for microencapsulating liquids and
solids of varied size ranges, with diverse
coating materials. The encapsulated product can
be supplied as slurry in the hardening media or s
a dry powder. Production rates of 50 to 75 pounds
per our have been achieved with the process.
25
POLYMERIZATION
A relatively new microencapsulation method
utilizes polymerization techniques to from
protective microcapsule coatings in situ. 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
liquidliquid, liquid-gas, solid-liquid, or
solid-gas interface.
26
POLYMERIZATION

• Monodisperse microgels in the micron or submicron
  size range.
• Precipitation polymerization starts from a
  homogeneous monomer solution in which the
  synthesized polymer is insoluble.
• The particle size of the resulting microspheres
  depends on the polymerization conditions,
  including the monomer/co monomer composition, the
  amount of initiator and the total monomer
  concentration.

27
EVALUATION OF MICROCAPSULES
Percentage Yield The total amount of
microcapsules obtained was weighed and the
percentage yield calculated taking into
consideration the weight of the drug and polymer
7. Percentage yield Amount of microcapsule
obtained / Theoretical Amount100 Scanning
electron microscopy Scanning electron
photomicrographs of drug loaded ethyl cellulose
microcapsules were taken. A small amount of
microcapsules was spread on gold stub and was
placed in the scanning electron microscopy (SEM)
chamber. The SEM photomicrographs was taken at
the acceleration voltage of 20 KV.
28
Particle size analysis For size distribution
analysis, different sizes in a batch were
separated by sieving by using a set of standard
sieves. The amounts retained on different sieves
were weighed 5. Encapsulation efficiency
8 Encapsulation efficiency was calculated
using the formula Encapsulation efficiency
Actual Drug Content / Theoretical Drug Content
100
29
Estimation of Drug Content
Cefotaxime sodium drug content in the
microcapsules was calculated by UV
spectrophotometric (Elico SL159 Mumbai India)
method. The method was validated for linearity,
accuracy and precision. A sample of microcapsules
equivalent to 100 mg was dissolved in 25 ml
ethanol and the volume was adjusted upto 100 ml
using phosphate buffer of pH 7.4. The solution
was filtered through Whatman filter paper. Then
the filtrate was assayed for drug content by
measuring the absorbance at 254 nm after suitable
dilution 9.
30
Invitro Drug release Studies
Drug release was studied by using USP type II
dissolution test apparatus (Electrolab TDT 08L)
in Phosphate buffer of pH 7.4 (900 ml). The
paddle speed at 100 rpm and bath temperature at
37 0.5c were maintained through out the
experiment. A sample of microcapsules
equivalent to 100 mg of cefotaxime sodium
was used in each test. Aliquot equal to 5ml of
dissolution medium was withdrawn at specific time
interval and replaced with fresh medium to
maintain sink condition. Sample was filtered
through Whatman No. 1 filter paper and after
suitable dilution with medium the absorbance was
determined by UV spectrophotometer (Elico SL159)
at 254 nm. All studies were conducted in
triplicate (n3). The release of drug from
marketed sustained release tablet was also
studied to compare with release from
microcapsules.
31
KINETIC ANALYSIS OF DISSOLUTION DATA
To study the mechanism of drug release from the
cefotaxime sodium microcapsules, the release
data were fitted to the following equations
(Time in each case was measured in minutes)
Model 1. Zero order kinetics Q1Q0
Kot Where, Q1-amount of drug dissolved in time
t Q0-initial amount of drug in the
solution K0-zero order release constant Model 2.
First order kinetics Ln Qr ln
Q0K1t Where, K1--first order release
constant Q0-initial amount of drug in the
solution Q1-amount of drug dissolved in time t
32
Model 3.Higuchi model Q tDCs (2c-Cs) Where, Q-
Amount of drug release in time t C- Initial drug
concentration Cs- drug solubility in the
matrix D- Diffusion constant of the drug molecule
in that liquid Model 5.Korsmeyer-Peppas Mt
M8 atn Where, a- constant incorporating
structural and geometric characteristics of the
drug dosage form n- the release exponent
(indicative of the drug release mechanism) Mt/M8-
fractional release of drug.
33
(No Transcript)