Coacervation Phase SeparationBY- GARGI NANDA

M. PHARM-1 (PT)ROLL NO. 01

GUIDED BY- MADAM KRUTIKA SAWANT

2Overview

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

3Introduction

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.

4Microencapsulation 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

5Coacervation 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.

6Steps of Coacervation

Formation of three

immiscible chemical phases

Deposition of the coating

Rigidization of the coating

7Overview of Coacervation

8Techniques Used for Coacervation

Change In Temperature

Incompatible Polymer Addition

Non-solvent Addition

Salt AdditionPolymer-Polymer

Interaction

9

Temperature ChangeUnder proper polymer concentration, temperature and agitation, liquid polymer coalesce around dispersed core and form embryonic micro particles.

10

Incompatible Polymer AdditionUsage of dissimilar polymer in common solvent can be done for preparation of micro particles.

11

Non-Solvent AdditionLiquid, which is non-solvent for polymer, is used for coacervation.

12

Salt AdditionSoluble inorganic salts are added to aqueous solutions of water soluble polymers for phase separation

13

Polymer InteractionInteraction of oppositely charged polyelectrolytes result in the formation of complex with reduced solubility that phase separation occurs.

14Modified Techniques of

CoacervationAqueous Phase Separation

Organic Phase Separation

Solvent Evaporation

Encapsulation by polyelectrolyte multilayer

Hydrogel Microsphere

Phase Inversion

Melt Dispersion

15Aqueous 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.

16Aqueous Phase

Separation (Contd.)

17Aqueous 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.

18Organic 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

19Organic Phase

Separation (Contd.)

20Organic Phase

Separation ExampleDissolve 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.

21Solvent 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.

22Solvent 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.

23Solvent Evaporation

Process (Contd.)

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.

25Polyelectrolye Multilayer

Technique

26Polyelectrolyte Multilayer

Technique Example Glucose oxidase has been microencapsulated

by alternate deposition of polyallylamine and polystyrene sulfonate layers.

27Hydrogel 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

28Hydrogel

MicroencapsulationPolymer (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.

29Hydrogel

Microencapsulation Technique

30Phase 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.

31Phase 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

32Melt 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.

33Melt Dispersion

Technique

34Reference

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

35Reference (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

36Reference (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

End