preparation method of microencapsulation

1. MICROENCAPSULATION TECHNIQUES
Presented by
Mr. Akshay M. Akotkar
Asst. Professor
Dept. Of Pharmaceutics
I.B.S.S.College of Pharmacy, Malkapur

2.  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 Macroparticles .
INTRODUCTION

3. Generally Micro particles consist of two components
a) Core material
b) Coating 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.  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.
Disadvantage-
 Agglomeration of the particles to some larger size is normally achieved.

5. FUNDAMENTAL CONSIDERATION:
Core material Coating material Vehicle
Solid Liquid
Microencapsulation
Polymers
Waxes
Aqueous Nonaqueous
Resins
Proteins
Polysaccharides

6. 1. Stabilization of core material.
2. Inert toward active ingredients.
3. Controlled release under specific conditions.
4. Film-forming, pliable, tasteless, stable.
5. Non-hygroscopic, no high viscosity, economical.
6. Soluble in an aqueous media or solvent, or melting.
7. The coating can be flexible, brittle, hard, thin etc.
Coating Material Properties

7. Water soluble
resin
Water insoluble
resin
Wax & lipid Enteric resin
Gelatin,
Gum arabic,
PVP,
CMC,
Methyl cellulose,
Arabinogalactan,
Polyvinyl
acrylate,
Polyacrylic acid.
Ethyl cellulose,
Polyethylene,
Polymethacrylate,
Cellulose nitrate,
Silicones.
Paraffin,
Carnauba wax,
Bees wax,
Stearic acid,
Stearyl alcohol.
Shellac,
Zein,
Cellulose
acetate
phthalate.
List of coating material

8. MICROENCAPSULATION TECHNIQUES:
Air suspension techniques( Wurster)
 Phase Seperation Co-acervation process
Solvent evaporation
 Spray drying & congealing
 Pan coating
 Polymerization
 Extrusion

9. Air-suspension coating
 Inventions by Professor Dale E. Wurster
 Basically 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.
 Equipment ranging in capacities from one pound to 990
pounds.
 Micron or submicron particles can be effectively encapsulated
by air suspension techniques.

10. WURSTER PROCESS:

11. Processing variables for efficient, effective encapsulation by air
suspension techniques:
1.Density, surface area, melting point, solubility, friability,
volatility, Crystallinity, and flow-ability of core 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 fluidizes the core material.
5.Amount of coating material required.
6.Inlet and outlet operating temperatures.

13. 2. Coacervation-Phase Separation
 Patents by B.K. Green et al.
The general process consist of 3 steps under continuous agitation:
1. Formation of 3 immiscible chemical phase
2. Deposition of coating
3. Rigidization of coating.
Step: 1) Three immiscible phases are as:
a) Liquid manufacturing vehicle phase
b) Core material phase
c) Coating material phase.
Coating material phase formed by utilizing following methods:
A) Temperature change.
B) By addition of incompatible polymer
C) By non-solvent addition
D) By salt addition
E) Polymer-polymer interaction.

14. Polymeric
Membrane
Droplets
Homogeneous
Polymer Solution
Coacervate
Droplets
PHASE
SEPARATION
MEMBRANE
FORMATION
1.Formation of three immiscible phase
2.Deposition of coating
3.Rigidization of coating.

15. COMPLEX COACERVATION :

16. 1. Solvent Evaporation
 In the case in which the core material is dispersed in the
polymer solution, polymer shrinks around the core. In the case
in which core material is dissolved in the coating polymer
solution, a matrix - type microcapsule is formed.
 The core materials may be either
water - soluble or
water - insoluble materials.
 A variety of film - forming polymers can be used as coatings.

17. Polymer
+ Volatile organic solvent
Organic Polymeric Phase
Formation of Oil-in-Water
Emulsion
Solvent Evaporation
Particle Formation by
Polymer Precipitation
RECOVERY OF POLYMERIC
MICROPARTICLES
Temperature increase
Active
Ingredient
Addition into an aqueous
phase (+o/w stabilizer)
SOLVENT EVAPORATIONS
Step 1:
Formation of a solution/dispersion of
the drug into an organic polymer
phase.
Step 2:
Emulsification of the
polymer phase into an aqueous phase
containing a suitable stabilizer, thus,
forming a o/w emulsion.
Step 3:
Removal of the organic
solvent from the dispersed phase by
extraction or evaporation leading to
polymer precipitation and formation
of the microspheres.

18. 4. Spray-drying
 In modern spray dryers the viscosity of the solutions to be sprayed can be as
high as 300mPa.s
 Spray drying and spray congealing- dispersing the core material in a liquefied
coating substance and spraying.
 Spray drying is effected by rapid evaporation of a solvent in which the coating
material is dissolved.
The equipment components of a standard spray dryer include
1. an air heater,
2. atomizer,
3. main spray chamber,
4. blower or fan,
5. cyclone and
6. product collector.

19.  Spray congealing can be accomplished with spray drying
equipment when the protective coating is applied as a melt.
 Core material is dispersed in a coating material melt rather
than a coating solution.
 Coating solidification (and microencapsulation) is
accomplished by spraying the hot mixture into a cool air
stream.

20. SPRAY DRYING & CONGEALING ( COOLING)
Spray drying : spray = aqueous solution / Hot air.
Spray congealing : spray = hot melt/cold air.

21. • The method involve the reaction of monomeric unit located at
the interface existing between a core material substance and
continuous phase in which the core material is disperse.
• The core material supporting phase is usually a liquid or gas,
and therefore polymerization reaction occur at liquid-liquid,
liquid-gas, solid-liquid, or solid-gas interface.
• E.g. In the formation of polyamide (Nylon) polymeric
reaction occurring at liquid-liquid interface existing between
aliphatic diamine & dicarboxylic acid halide.
Polymerization

22. Drug
Addition of the alcoholic solution
of the initiator (e.g., AIBN)
8 hrs Reaction time
Monomer(s) (e.g. acrylamide, methacrylic acid)
+ Cross-linker (e.g. methylenebisacrylamide)
Alcohol
T (reaction) = 60 °C
Nitrogen Atmosphere
Preparation of the
Polymerization Mixture
Initiation of
Polymerization
Monodisoerse Latex
Formation by Polymer
Precipitation
RECOVERY OF POLYMERIC
MICROPARTICLES
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.
POLYMERIZATION:

24.  Oldest industrial procedures for forming small, coated particles
or tablets.
 The particles are tumbled in a pan or other device while the
coating material is applied slowly.
 Solid particles greater than 600 microns in size are generally
considered essential for effective coating.
 Medicaments are usually coated onto various spherical
substrates such as nonpareil sugar seeds, and then coated with
protective layers of various polymers.
Pan coating

26. MULTIORIFICE-CENTRIFUGAL PROCESS
The Southwest Research Institute (SWRI) has developed this method.
 It is a mechanical process for producing microcapsules.
centrifugal forces are used to hurl a core material particle through
an enveloping microencapsulation membrane.
Processing variables include:
the rotational speed of the cylinder,
the flow rate of the core and coating materials,
the concentration, viscosity, 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
- dry powder.
Production rates of 50 to 75 pounds per hour.

28.  This method was first patented in 1957.
 The advantage of extrusion is that it completely surrounds the core
material with wall material.
 The process involves forcing a core material dispersed in a molten
carbohydrate mass through a series of dies, into a bath of
dehydrating liquid.
 When contact with the liquid is made, the carbohydrate case
hardens to entrap the core material.
 The extruded filaments are separated from the liquid bath, dried
using an anti-caking agent such as calcium tripolyphosphate and
sized .
 This process is particularly useful for heat labile substances such as
flavours, vitamin C and colours.

29. NOZZLE VIBRATION TECHNOLOGY :

31. APPLICATION OF MICROENCAPSULATION:
 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,
Aspirin.

32. APPLICATION OF MICROENCAPSULATION TECHNIQUES:

33. EVALUATION OF MICROCAPSULES
1. MORPHOLOGY:
The surface morphologies of microspheres are examined by a scanning electron
microscope.(SEM)
2. PARTICLE SIZE:
The microparticle size can be determined by laser diffractometry.
Approximately 30 mg microparticles is redispersed in 2–3 ml distilled water,
containing 0.1% (m/m) Tween-20 for 3 min, using ultrasound.
then transferred into the small volume recirculating unit, operating at 60 ml/ s. in
Laser Diffractometry.
Or either by Particle size analyser.

34. EVALUATION OF MICROCAPSULEs
3. BULK DENSITY:
The bulk density is estimated by Bulk Density Apparatus.
The microspheres fabricated are weighed and transferred to a 10-ml glass
graduated cylinder.
The cylinder is tapped until the microsphere bed volume is stabilised.
The bulk density is estimated by the ratio of microsphere weight to the final
volume of the tapped microsphere bed.
4. LOADING EFFICIENCY:
The capture efficiency of the microspheres or the percent entrapment can be
determined by allowing washed microspheres to lysate.
 The lysate is then subjected to the determination of active constituents as per
monograph requirement.
The percent encapsulation efficiency is calculated using equation:
% Entrapment = Actual content/Theoretical content x 100

35. 5. Flow Properties of microcapsules:
Flow properties of microcapsules can be determined by Angle of repose.
The angle of repose is determined by Fixed Funnel method method.
6. IN VITRO RELEASE PROFILE:
For this purpose, a number of in vitro and in vivo techniques have been
reported.
Release characteristics and permeability of a drug through membrane to be
determined.
In vitro drug release studies are employed as a quality control procedure in
pharmaceutical production, in product development etc.
Dissolution profile is performed depending on the shape and application of the
dosage form developed.
Standard USP or BP dissolution apparatus have been used to study in vitro
release profiles.
Dissolution medium used for the study varied from 100-500 ml