MICROENCAPSULATION shivakumar B.pharmacy kottam institute of pharmacy, A.P
INTRODUCTION Microencapsulation is a process by which very tiny droplets orparticles of liquid or solid material are surrounded or coated with a continuousfilm 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.
CLASSIFICATION OF MICROPARTICLE 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.
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.
FUNDAMENTAL CONSIDERATION: Microencapsulation Core material Coating material VehicleSolid Liquid Polymers Aqueous Nonaqueous Waxes Resins Proteins Polysaccharides
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
Air Suspension Techniques( Wurster)Microencapsulation by air suspension technique consistof the dispersing of solid, particulate core materials in asupporting air stream and the spray coating on the airsuspended particles. Within the coating chamber,particles are suspended on an upward moving air stream.The design of the chamber and its operating parameterseffect a recalculating flow of the particles through thecoating zone portion of the chamber, where a coatingmaterial, usually a polymer solution, is spray applied tothe moving particles.
During each pass through the coating zone, the corematerial receives an increment of coating material.The cyclic process is repeated, perhaps severalhundred times during processing, depending on thepurpose of microencapsulation the coatingthickness desired or whether the core materialparticles are thoroughly encapsulated. Thesupporting air stream also serves to dry the productwhile it is being encapsulated. Drying rates aredirectly related to the volume temperature of thesupporting air stream.
Coacervation processFormation of three immiscible phases; a liquid manufacturingphase, 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 ordesolvation techniques to form a microcapsule.In step 2, the deposition of the liquid polymer around the interfaceformed between the core material and the liquid vehicle phase. Inmany cases physical or chemical changes in the coating polymersolution can be induced so that phase separation of the polymerwill occur.
Droplets of concentrated polymer solution will form and coalesce toyield a two phase liquid-liquid system. In cases in which the coatingmaterial is an immiscible polymer of insoluble liquid polymer it maybe added directly. Also monomers can be dissolved in the liquidvehicle phase and subsequently polymerized at interface.Equipment required for microencapsulation this method is relativelysimple; it consists mainly of jacketed tank with variable speedagitator.
COACERVATION / PHASE SEPARATION Coacervate Droplets SEPARATION FORMATION PHASE MEMBRANE Droplets Polymer Solution1.Formation of three immiscible phase Membrane Polymeric Homogeneous2.Deposition of coating3.Rigidization of coating.
Spray-Drying & spray-congealingSpray-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-congealingSpray-congealing:-This technique can be accomplished with spray dryingequipment 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) isaccomplished by spraying the hot mixture into a cool airstream.- e.g. microencapsulation of vitamins with digestiblewaxes for taste masking.
SPRAY DRYING & CONGEALING ( COOLING) Spray drying : spray = aqueous solution / Hot air Spray congealing : spray = hot melt/cold air
PAN COATING1- Solid particles are mixed with a dry coatingmaterial.2- The temperature is raised so that the coatingmaterial melts and encloses the core particles, andthen is solidified by cooling.Or, the coating material can be gradually applied tocore particles tumbling in a vessel rather than beingwholly mixed with the core particles from the start ofencapsulation.
MULTIORIFIC-CENTRIFUGAL PROCESSThe 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.
POLYMERIZATIONA 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: Drug Monomer(s) (e.g. acrylamide, methacrylic acid) Monodisperse microgels in the micron or + Cross-linker (e.g. methylenebisacrylamide) submicron size range. Preparation of the Polymerization Mixture Alcohol Precipitation polymerization starts from Addition of the alcoholic solution a homogeneous monomer solution in of the initiator (e.g., AIBN) which the synthesized polymer is insoluble. Initiation of Polymerization The particle size of the resulting 8 hrs Reaction time microspheres depends on the polymerization conditions, including the Monodisoerse Latex Formation by Polymer monomer/co monomer composition, the Precipitation amount of initiator and the total T (reaction) = 60 °C monomer concentration. Nitrogen Atmosphere RECOVERY OF POLYMERIC MICROPARTICLES
EVALUATION OF MICROCAPSULESPercentage YieldThe total amount of microcapsules obtained was weighed andthe percentage yield calculated taking into consideration theweight of the drug and polymer .Percentage yield = Amount of microcapsule obtained /Theoretical Amount×100Scanning electron microscopyScanning electron photomicrographs of drug loaded ethylcellulose microcapsules were taken. A small amount ofmicrocapsules was spread on gold stub and was placed in thescanning electron microscopy (SEM) chamber.The SEM photomicrographs was taken at theacceleration voltage of 20 KV.
Particle size analysisFor size distribution analysis, different sizes in abatch were separated by sieving by using a set ofstandard sieves. The amounts retained ondifferent sieves were weighed .Encapsulation efficiency Encapsulation efficiency was calculated usingthe formula:Encapsulation efficiency = Actual Drug Content /Theoretical Drug Content ×100
Estimation of Drug ContentCefotaxime sodium drug content in the microcapsules wascalculated by UV spectrophotometric (Elico SL159 MumbaiIndia) method. The method was validated for linearity, accuracy andprecision. A sample of microcapsules equivalent to 100 mgwas dissolved in 25 ml ethanol and the volume wasadjusted upto 100 ml using phosphate buffer of pH 7.4. Thesolution was filtered through Whatman filter paper. Then thefiltrate was assayed for drug content by measuring theabsorbance at 254 nm after suitable dilution .
Invitro Drug release StudiesDrug release was studied by using USP type II dissolution test apparatus(Electrolab TDT 08L) in Phosphate buffer of pH 7.4 (900 ml). The paddlespeed at 100 rpm and bath temperature at 37 ± 0.5°c were maintainedthrough 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 waswithdrawn at specific time interval and replaced with fresh medium tomaintain sink condition. Sample was filtered through Whatman No. 1 filterpaper and after suitable dilution with medium; the absorbance wasdetermined by UV spectrophotometer (Elico SL159) at 254 nm.All studies were conducted in triplicate (n=3). The release of drug frommarketed sustained release tablet was also studied to compare withrelease from microcapsules.
KINETIC ANALYSIS OF DISSOLUTION DATATo study the mechanism of drug release from the cefotaxime sodium microcapsules,the release data were fitted to the following equations: (Time in each case wasmeasured in minutes)Model 1. Zero order kineticsQ1==Q0 + KotWhere,Q1-amount of drug dissolved in time tQ0-initial amount of drug in the solutionK0-zero order release constantModel 2. First order kineticsLn Qr = ln Q0K1tWhere,K1--first order release constantQ0-initial amount of drug in the solutionQ1-amount of drug dissolved in time t
Model 3.Higuchi modelQ= tDCs (2c-Cs)Where,Q- Amount of drug release in time tC- Initial drug concentrationCs- drug solubility in the matrixD- Diffusion constant of the drug molecule in that liquidModel 5.Korsmeyer-Peppas Mt M∞ = atnWhere,a- constant incorporating structural andgeometric characteristics of the drug dosage formn- the release exponent (indicative of the drugrelease mechanism)Mt/M∞- fractional release of drug.