This document provides an overview of microencapsulation techniques with a focus on coacervation phase separation. It defines coacervation as the partial desolvation of a homogeneous polymer solution into a polymer-rich phase and poor polymer phase. The key steps of coacervation formation are the formation of three immiscible chemical phases, deposition of the coating, and rigidization of the coating. Various techniques used for coacervation include changes in temperature, addition of incompatible polymers, addition of non-solvents, addition of salts, and polymer-polymer interactions. Modified coacervation techniques discussed include aqueous phase separation, organic phase separation, solvent evaporation, encapsulation by polyelectrolyte multilayer, hydrogel micro

1. Coacervation Phase
Separation
BY- GARGI NANDA
M. PHARM-1 (PT)
ROLL NO. 01
GUIDED BY- MADAM KRUTIKA SAWANT

2. Overview
 Introduction
 Coacervation Phase Separation
 Techniques for Coacervation
 Modified Techniques for Coacervation
 Aqueous Phase Separation
 Organic Phase Separation
 Solvent Evaporation
 Polyelectrolyte Multilayer
 Hydrogel
 Phase Inversion
 Melt Dispersion
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3. Introduction
 Micro-encapsulation is a process in which
tiny particles or droplets are surrounded by a
coating to give small capsules of many useful
properties. It can also be used to enclose
solids, liquids, or gases inside a micrometric
wall made of hard or soft soluble film, in order
to reduce dosing frequency and prevent the
degradation of pharmaceuticals.
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4. Microencapsulation
Techniques
Physicochemical
Coacervation
Phase Separation
Polymer
Incompatibility
Ionotropic
Gelation
Physicomechanical
Spray Drying
Fluidized Bed
Technology
Pan Coating
Spinning Disc
Co-extrusion
Chemical
Interfacial
Polymerisation
In-situ
Polymerisation
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5. Coacervation Phase
Separation
 Coacervation Phase Separation refers to 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 ›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.
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6. Steps of Coacervation
Formation of
three
immiscible
chemical
phases
Deposition of
the coating
Rigidization of
the coating
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7. Overview of Coacervation 7

8. Techniques Used for
Coacervation
Change In
Temperature
Incompatible
Polymer
Addition
Non-solvent
Addition
Salt Addition
Polymer-
Polymer
Interaction
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9. Temperature
Change
Under proper polymer
concentration,
temperature and
agitation, liquid
polymer coalesce
around dispersed core
and form embryonic
micro particles.
9

10. Incompatible
Polymer Addition
Usage of dissimilar
polymer in common
solvent can be done
for preparation of micro
particles.
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11. Non-Solvent
Addition
Liquid, which is non-
solvent for polymer, is
used for coacervation.
11

12. Salt Addition
Soluble inorganic salts
are added to aqueous
solutions of water
soluble polymers for
phase separation
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13. Polymer
Interaction
Interaction of
oppositely charged
polyelectrolytes result
in the formation of
complex with reduced
solubility that phase
separation occurs.
13

14. Modified Techniques of
Coacervation
Aqueous Phase Separation
Organic Phase Separation
Solvent Evaporation
Encapsulation by polyelectrolyte
multilayer
Hydrogel Microsphere
Phase Inversion
Melt Dispersion
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15. Aqueous Phase Separation
 The term aqueous phase separation is often more
simply described as "oil-in-water" microencapsulation.
In this process the core material is the oil and it should
be immiscible in the continuous phase, namely water.
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16. Aqueous Phase Separation
(Contd.)
16

17. Aqueous Phase Separation
Example
 A commercial example of aqueous phase separation
would be the microencapsulation of an oily flavour
such as sour cream with a gelatine wall. These
microcapsules would then be dispersed in a dry cake
mix. The mechanism of release would be during the
moist baking cycle of the cake, moist-heat causing the
capsule walls to first swell and then rupture.
17

18. Organic Phase Separation
 The term organic phase separation' is sometimes more simply
referred to as "water-in-oil" microencapsulation. In this case the
polar core is dispersed into an oily or non-polar continuous
medium. The wall material is then dissolved in this continuous
medium.
 Process Comprises of:
 Providing an aqueous phase comprising a material to be
encapsulated
 Creating an emulsion of said aqueous phase in a continuous
organic liquid phase comprising one or more organic solvents and
one or more surface active agents, wherein the emulsion comprises
discrete droplets of the aqueous phase dispersed in the continuous
phase organic liquid, there being formed thereby an interface
between the discrete droplets of the aqueous phase and the
continuous organic liquid phase
18

19. Organic Phase Separation
(Contd.)
19

20. Organic Phase Separation
Example
Dissolve ethyl cellulose in cyclohexane at 50°C
with continuing mixing.
Cyclohexane is the oily, continuous phase and
the ethyl cellulose will later form the coacervative
wall.
The temperature is elevated to 70°C over a
period of 20 to 30 minutes.
The core material is added and the temperature
raised to 80°C and is held at that temperature for
one hour.
The system is allowed to cool rapidly to 20-40°C.
20

21. Solvent Evaporation
 Microcapsule formation by solvent evaporation/solvent
extraction is very similar to suspension crosslinking,
but in this case the polymer is usually hydrophobic
polyester.
 It facilitates a controlled release of a drug, which has
many clinical benefits. Water insoluble polymers are
used as encapsulation matrix using this technique.
Biodegradable polymer PLGA (poly (lactic-co-glycolic
acid)) is frequently used as encapsulation material.
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22. Solvent Evaporation Process
Microspheres are washed and dried.
Emulsion is constantly stirred till organic solvent evaporates, giving microspheres.
Formed emulsion is added to large amount of water having emulsifier (PVA) to
form multiple emulsion.
Organic phase having polymer solution is added in solvents like chloroform with
stirring.
Aqueous solution of drug is prepared.
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23. Solvent Evaporation Process
(Contd.)
23

24. Encapsulation By
Polyelectrolyte
Multilayer
Sequentially immerse a
substrate in positively
and negatively charged
polyelectrolyte solutions
in a cyclic procedure.
Core shell particles with
tailored size and properties
are prepared using colloidal
particles as the core material
that serves as a template
onto which multilayers are
fabricated.
Hollow capsules of organic,
inorganic or hybrid particles
can be obtained by
dissolving the core material.
This technique is both
versatile and simple, with the
multilayer film thickness being
controlled precisely by
varying the total number of
layers deposited. In this way
the final properties can be
tuned.
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25. Polyelectrolye Multilayer
Technique
25

26. Polyelectrolyte Multilayer
Technique Example
 Glucose oxidase has been microencapsulated by
alternate deposition of polyallylamine and polystyrene
sulfonate layers.
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27. Hydrogel Microspheres
 Hydrogels have been used in numerous biological
technologies including gel electrophoresis and cell
encapsulation.
 In cell encapsulation, the matrix material defines the
extracellular environment and likely impacts cell
viability, function, growth, and differentiation. The
matrix may provide the required growth substrate for
anchorage-dependent cells or the appropriate
immobilization needed by suspension cells. Numerous
hydrogels have been used for cell encapsulation
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28. Hydrogel
Microencapsulation
Polymer (eg.
Alginates) are
dissolved in an
aqueous solution.
Active ingredient is
suspended in the
mixture.
Through a precise
device, extrusion
is done to form
microdroplets.
Microdroplets fall
into hardening
bath that is slowly
stirred.
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29. Hydrogel
Microencapsulation
Technique
29

30. Phase Inversion
 Phase inversion is a term used to describe the
physical phenomena by which a polymer dissolved in a
continuous phase solvent system inverts into a solid
macromolecular network in which the polymer is the
continuous phase.
 Phase inversion phenomenon have been applied to
produce macro and microporous polymer membranes
and hollow fibers used in gas separation, ultrafiltration,
ion exchange, and reverse osmosis.
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31. Phase Inversion Process
Polymer solution
undergoes transition
from single phase
homogenous solution to
two phase mixture
Micellar droplets serve
as nucleation sites and
coat with polymer
At critical concentration
of polymer, droplets
precipitate and solidify.
In favourable conditions,
micelles coalesce and
precipitate to form
continuous polymer
network
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32. Melt Dispersion
 In this technique the coating material is melted by
heating upto 80oC.
 The drug is suspended in it and then emulsified in
water containing emulsifying agent at 80oC under
stirring.
 Microcapsules are formed as the temperature of the
system reaches to room temperature.
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33. Melt Dispersion Technique 33

34. Reference
 Indian Journal of Research in Pharmacy and
Biotechnology Volume 1(3) May-June 2013 Page 324
 MICROENCAPSULATION TECHNOLOGY
 K.P.Sampath Kumar,Tejbe.Sk , Shameem Banu, P.Naga
Lakshmi, D.Bhowmik
 International Journal of Pharma and Bio Sciences
MICROENCAPSULATION: A REVIEW
 JYOTHI SRI.S, A.SEETHADEVI , K.SURIA PRABHA,
P.MUTHUPRASANNA AND ,P.PAVITRA
 Microencapsulation Technology and Applications
Rama Dubey, T.C. Shami and K.U. Bhasker Rao
34

35. Reference (Contd.)
 Internet Scientific Publications Microencapsulation
Techniques, Factors Influencing Encapsulation
Efficiency: A Review
 N Jyothi, M Prasanna, S Prabha, P Seetha Ramaiah, G
Srawan, S Sakarka
 Indo Global Journal of Pharmaceutical Sciences, 2012;
2(1): 1-20 1 Microencapsulation – A Novel Approach in
Drug Delivery: A Review Nitika Agnihotri, Ravinesh
Mishra*, Chirag Goda, Manu Arora
 Stability of Hydrogels Used in Cell Encapsulation: An In
Vitro Comparison of Alginate and Agarose Molly S.
Shoichet,* Rebecca H. Li, Melissa L. White, and Shelley
R. Winn
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36. Reference (Contd.)
 The Theory and Practice of Industrial Pharmacy;
Lachman and Leibermann; 3rd Edition
 www.authorstream.com
 en.wikipedia.org
 Patent US6143211; Google Patents
 Patent US6113935; GooglePatents
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37. En
d