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 .

INTRODUCTION

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CLASSIFICATION OF MICROPARTICLE

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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.

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ADVANTAGES:

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.

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FUNDAMENTAL CONSIDERATION:

Core material Coating material Vehicle

Solid Liquid

Microencapsulation

Polymers

Waxes

Aqueous Nonaqueous

Resins

Proteins

Polysaccharides

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APPLICATION OF MICROENCAPSULATION TECHNIQUES:

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Medicine & Pharmacy & vetinaryControl release, Taste maskingVectorisationArtificial organssingle dose treatment

Medicine & Pharmacy & vetinaryControl release, Taste maskingVectorisationArtificial organssingle dose treatment

Microencapsulation : Applications

ChemistryPrinting & recordingCarbonless paper,AdhesivesPigments and Fillers Catalysts

Food & feedAromas, ProbioticsUnsaturated oil,Enzyme food processingamino acid for cows

AgricultureFungicide – herbicide, Insect repellent, BiopesticidePigments and fillersArtificial insemination

Biotechnology & environmentContinuous reactor,Shear protection,Reactor oxygenation

Consumer & diversifiedCosmetics,detergents (enzymes),sanitary (active, aromas)

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MICROENCAPSULATION TECHNIQUES:

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RELEASE MECHANISMS

1. Degradation controlled monolithic system

2. Diffusion controlled monolithic system

3. Diffusion controlled reservoir system

4. Erosion

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 T.B.EKNATH BABU 10

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.

Air Suspension Techniques( Wurster)

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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.

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Air suspension techniques (WURSTER PROCESS):

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Coacervation processFormation 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.

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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.

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COACERVATION / PHASE SEPARATION

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PolymericMembrane

DropletsHomogeneousPolymer Solution

CoacervateDroplets

PHASE

SEPARATION

MEMBRANE

FORMATION

1.Formation of three immiscible phase

2.Deposition of coating

3.Rigidization of coating.

COMPLEX COACERVATION :

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Spray-Drying & spray-congealing :

- Microencapsulation by spray-drying is a low-cost commercialprocess which is mostly used for the encapsulation of fragrances,oils and flavors.

Steps:1- Core particles are dispersed in a polymer solution and sprayed intoa hot chamber.

2- The shell material solidifies onto the core particles as the solventevaporates.- The microcapsules obtained are of polynuclear or matrix type.

Spray-Drying & spray-congealing

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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 digestiblewaxes for taste masking.

Spray-congealing

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Spray-Drying

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SPRAY DRYING & CONGEALING ( COOLING)

Spray drying : spray = aqueous solution / Hot air

Spray congealing : spray = hot melt/cold air

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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.

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The Southwest Research Institute (SWRI)has developed a mechanical process forproducing microcapsules that utilizescentrifugal forces to hurl a core materialparticle trough an envelopingmicroencapsulation membrane therebyeffecting mechanical microencapsulation.Processing variables include the rotationalspeed of the cylinder, the flow rate of thecore and coating materials, theconcentration and viscosity and surfacetension of the core material. Themultiorifice-centrifugal process is capablefor microencapsulating liquids and solidsof varied size ranges, with diverse coatingmaterials. The encapsulated product can besupplied as slurry in the hardening mediaor s a dry powder. Production rates of 50to 75 pounds per our have been achievedwith the process.

MULTIORIFIC-CENTRIFUGAL PROCESS

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A relatively new microencapsulationmethod utilizes polymerization techniquesto from protective microcapsule coatingsin situ. The methods involve the reactionof monomeric units located at the interfaceexisting between a core material substanceand a continuous phase in which the corematerial is dispersed. The continuous orcore material supporting phase is usually aliquid or gas, and therefore thepolymerization reaction occurs at a liquidliquid,liquid-gas, solid-liquid, or solid-gasinterface.

POLYMERIZATION

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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:

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Percentage YieldThe 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 Amount×100

Scanning electron microscopyScanning 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 theacceleration voltage of 20 KV.

EVALUATION OF MICROCAPSULES

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Particle size analysisFor size distribution analysis, different sizes in abatch were separated by sieving by using a set of standard sieves. The amounts retained ondifferent sieves were weighed [5].

Encapsulation efficiency [8]Encapsulation efficiency was calculated usingthe formula:Encapsulation efficiency = Actual Drug Content / Theoretical Drug Content ×100

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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 wasadjusted 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].

Estimation of Drug Content

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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 ± 0.5°c were maintained through out the experiment.

A sample of microcapsules equivalent to 100 mg of cefotaxime sodium wasused 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 (n=3). The release of drug from marketed sustained release tablet was also studied to compare with release from microcapsules.

Invitro Drug release Studies

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THANKYOUAS

EKNATH BABU STUDENT AT ARULMIGU

KALASALINGAM COLLEGE OF PHARMACY

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