MICROENCAPSULATION

By SANA TABASSUM (B.Pharm)

Under the guidance ofMrs.Ch.S VIJAYA VANI,M.Pharm.

Associate Professor,Department of Pharmaceutics.

A Presentation

On

CMR COLLEGE OF PHARMACY

DEFINITIONMicroencapsulation is the process by which tiny solid particles or droplets of liquid are surrounded or coated with a continuous film of polymeric material to produce capsules in the micrometer to millimeter range. The product obtained by this process is called as microcapsules.1 Microcapsule

MICROCAPSULES

Microcapsules in blood stream

Microscopic view of microcapsules

Advantages of microencapsulationMasking of bitter taste drugs. Eg: Ofloxacin.Conversion of liquid to pseudo solid. Eg: Eprazinone.2

Environmental protection.Eg: Vit.A.Palmitate. Reduction of hygroscopicity .Eg: NaCl. Reduction of vaporization of volatile drugs. Eg: Methyl salicylate.Prevention of incompatibilities among drugs. Eg: Aspirin and Chlorpheniramine maleate .2

Disadvantages of Microencapsulation.

Possible cross reaction between core and shell material.Difficult to achieve continuous and uniform film.Shelf life of hygroscopic drugs is reduced.More production costs.More skill and knowledge is required.2

MECHANISMS OF DRUG RELEASE

Degradation controlled monolithic system

Diffusion controlled monolithic system

Diffusion controlled reservoir system

Erosion

MECHANISMS OF DRUG RELEASE1)Degradation controlled monolithic

system-Drug releases on degradation of matrix.

2)Diffusion controlled monolithic system-Drug released by diffusion then degradation of matrix occurs.

3)Diffusion controlled reservoir system-Drug from capsule diffuses then rate controlling membrane erodes.

4)Erosion-Due to pH and enzymatic hydrolysis.2

CLASSIFICATION OF MICROCAPSULES2

Mononuclear Polynuclear Matrix Mononuclear with multiple shells

MATERIALS INVOLVED IN FORMULATION

A)Core Material:Specific material to be coated.It may be liquid or solid. Liquid core may be dissolved or dispersed material.3

Core Material Purpose Final Product Form

Acetaminophen Taste masking Tablet

Potassium chloride

Reduces gastric irritation

Capsule

Isosorbide dinitrate

Sustained release

Capsule

Examples of core material

B)Coating Material: Inert substance which coats on core with desired thickness.

Composition of coating solution•Inert polymer.•Plasticizer- Triethylcitrate, glycerin•Solvents- Water,cyclohexane.•Co solvents-Glycerol, sorbitol.

Examples of various coating material 3

Category of Coating Material

Examples

Water soluble resins Gelatin, Polyvinylpyrrolidone(PVP).

Water insoluble resins Ethyl cellulose, Polyethylene.Waxes and lipids Paraffin, Carnauba, Beeswax.Enteric resins Shellac, Zein.

TECHNIQUES TO MANUFACTURE MICROCAPSULES

S.No Physical Methods Chemical Methods

A) Air Suspension Solvent EvaporationB) Pan Coating PolymerizationC) Coarcervation Phase

Separation Interfacial

Polymerization In-situ PolymerizationD) Multi-orifice

Centrifugal ProcessE) Spray Drying & Spray

CongealingF) Fluidized Bed

Technology

A)Air Suspension(Wurster Method)Within the coating chamber, particles are suspended on an upward moving air stream.

Spraying of coating material on the air suspended particles.

The cyclic process is repeated depending upon purpose of microencapsulation.

Air stream serves to dry the product.3

Advantages: Disadvantages:Various coating material can be used.

Applicable only to solid core material.

Capacity is more

Agglomeration of the particles

WURSTER APPARATUS

B) Pan Coating

The particles are tumbled in a pan while the coating material is applied slowly as solution or atomized spray to the core.

To remove the coating solvent, warm air is passed over the coated materials or dusting of talc is done.

Medicaments are usually coated onto nonpareil sugar seeds and then coated with polymers.3

Advantages: Disadvantages:Suitable to larger particles.

Time consuming.

Sustained release preparations.

High material loss.

C) Coacervation Phase Separation:

Simple coacervation Complex coacervationA desolvation agent is added for phase separation

It involves complexation between two oppositely charged polymers.

Steps involved in this process are:-1) Formation of three immiscible phases.2) Deposition of liquid coating material upon

the core material.3) Rigidization of coating.

Coacervation process

Various methods to obtain three immiscible phases:

1) Temperature change2) Incompatible Polymer Addition3) Non-Solvent Addition4) Salt Addition5) Polymer-Polymer Interaction(Complex Coacervation)

Temperature change:

Temperature-composition phase

diagram for a binary system of a polymer

and a solvent.

TEM

PERA

TURE

POLYMER CONCENTRATION %

XA

BC D

E

F G

•Point X represents –single phase.

The phase-boundary curve indicates that with decreasing temperature.

One phase becomes polymer rich.

Other phase becomes polymer poor.

Eg: N-acetyl p-amino phenol.4

Non-Solvent Addition:

A liquid that is a non-solvent for a given polymer can be added to a solution of the polymer to induce phase separation.

Eg: Addition of isopropyl ether to CAB dissolved in methyl ethyl ketone.Core: Methyl scopolamine HBr.4

XA

BC

D E

SOLVENT 100%

100%POLYMER

100%NON SOLVENT

Phase diagram for phase-separation/

coacervation induced by Non Solvent

Addition

Salt Addition

Soluble inorganic salts can be added to aqueous solutions of water-soluble polymers .Eg: Sodium sulfate,Core-Vitamin in corn oil.4

Polymer-Polymer Interaction (Complex Coacervation):Steps involved:4

1. Formation of an O/W emulsion

2. Formation of the coating

3. Stabilization of the coating

A

CB

WATER100%

100%P -

100%P+

Ternary Phase diagram

X

D) Multi-orifice Centrifugal Process

Advantages:Encapsulates both solid and liquid materials.Production rate is more.

It utilizes centrifugal forces to hurl a core material particle through an enveloping microencapsulation membrane .4

E) Spray Drying and Spray Congealing:

Spray Drying Spray CongealingCoating solidification effected by rapid evaporation of solvent in which coating material is dissolved.

Coating solidification is effected by thermally congealing a molten coating material.4

Advantages:Low bulk density product.Porous nature capsules.Free flowing particles.

F) Solvent Evaporation

Advantages:Encapsulation of hydrophobic and hydrophilic drug.Simple technique.Encapsulation of solid and liquid drug.

G) Polymerization

Interfacial Polymerization In-situ Polymerization

NOVEL METHODSA) Vibration Technology

A fluid stream of liquid core and shell materials is pumped through concentric tubes and forms droplets under the influence of vibration. 1

B) Jet Cutter TechnologyA solid jet of fluid coming out of a nozzle by means of rotating cutting wires is cut into cylindrical segments which then form beads due to surface tension on their way to a hardening device.1

C) Rapid Expansion Of Super Critical Solution(RSS)Core and the shell material are maintained at high pressure and then released at atmospheric pressure through a small nozzle.

Sudden drop in pressure causes desolvation of the shell material.1

APPLICATIONSTo reduce gastric and other GIT irritations. Eg: Aspirin preparations.Prolonged release dosage forms preparation. Preparation of enteric-coated dosage forms .Replacement of therapeutic agents (not taken orally like insulin), gene therapy and in use of vaccines for treating AIDS, tumors, cancer and diabetes.Delivery of DNA vaccines.Prodrug approach. Eg: Minocycline HCl.Biodegradable and biocompatible microparicles preparations.Example: Risperidone or testosterone.5

Marketed formulations prepared using microcapsules5

S.No Brand Name

Generic Name

Categoryof drug

1. Lupin Cefadroxil Antibiotic

2. ZORprin CR Aspirin Anti-arthritic

3. Glipizide SR Glucotrol Anti diabetic

REFERENCES1. http://www.authorstream.com/Presentation/vivekchauhan-

1147305-microencapsulation.2. Hammad umer et.al,” International Journal of Research in

Pharmaceutical and Biomedical Sciences” ISSN: 2229-3701.

3. S. S. Bansode et.al,” Institute of Pharmaceutical Education And Research”, Volume 1, Issue 2, March –April 2010; Article 008 .

4. Lachman LA, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Mumbai, India: Varghese Publishing House; 3:414-415.

5. http://www.authorstream.com/Presentation/thokesagar-1295371-shree/

THANK

YOU