disover the science of : ~micro encapsulation~ group- 9 ( bito )
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Definition
The technique of microencapsulation depends on the physical and chemical properties of the material to be encapsulated.
Microencapsulation is a process in which very small droplets or particles of solid or liquid substances are surrounded by a coating to make microcapsules with useful properties.
Barrett K. Green (September 11,1906 - August 29,1997) was an American scientist, innovator
Industry pioneer who is best known as the inventor of microencapsulation. Gave birth to a whole new industry.
Green was a long-time national cash register company (NCR) employee (1933-1973)
Held 197 patents, and was highly respected and honored scientist.
Barrett K. Green
History
Pressure from a writing implement (pen or pencil) broke the microcapsules of dye on the underside of each sheet (except the last one); when the dye was released, it reacted with acidic layer on the surface of the next sheet and became visible.
Carbonless paper: The product had three layers: 1. The paper2. A film of acid-sensitive dye packaged
in microcapsules and 3. A layer of acidic clay to develop the
dye from transparent to dark blue or black.
• Developed microcapsules by coacervation • Developed a solid gelatin sphere with an il-phase as core with colourless
dye base dissolved.
Core material:
(the intrinsic part)
contains the active ingredient which may be solid, liquid or gas in the form of a solution,
dispersion or emulsion.
Coat or film or shell:
(the extrinsic part)
protects the core permanently or temporarily from the
external atmosphere. This may be permeable, semi permeable
or impermeable. Polymers, waxes resins, proteins,
polysaccharides.
Components of a Microparticle
Classification on basis of Morphology:
Core Material
Shell Material
Core Material
Shell Material
Continuous Core/ mononuclear microcapsule
polynuclear Microcapsule
•with a continuous core region surrounded by a continuous shell.
Spherical
•with a number of small droplets or particles of core material surrounded by a matrix of the coating agent
Geometrically irregular
•the core material is distributed homogeneously into the shell material
Matrix
Matrix microcapsule
Core Material
Classification on basis of Size
• Particles having diameter between 3-8 micrometer are called microparticles or microspheres or microcapsules.
• Particles larger than 1000 micrometer are called macroparticles.
Reasons for Microencapsulation
1.
•To protect reactive substances from the environment
2.
•To convert liquid active components into a dry solid system
3.
•To separate incompatible components for functional reasons
4.
•To control release of the active components for delayed (timed) release or long-acting (sustained) release
Pan Coating
• The pan coating process is amongst the oldest industrial mechanisms used particularly in the pharmaceutical industry for forming small, coated particles or tablets.
• The particles are tumbled in a pan or other device while the coating material is applied slowly.
• The pipe of the blower stretches into the pot for an even heating distribution while the coating pan is rotating.
Fluid Bed Coating(Wurster Coating)• Particles of the active ingredient, spheres
or granules, are suspended in an upward-moving stream of air and then covered with a spray of liquid coating material.
• The capsules are then shifted to an area where their shells are solidified by cooling or solvent vaporization.
• The whole cycle of suspending, spraying and cooling is repeated until the capsule’s walls are of the desired thickness.
• The size of the core particle for this technique is usually large (~100 microns).
• This technique gives improved flexibility and control as compared to pan coating.
Uses and Benefits:
Pharmaceutical Industry
Food IndustryVitamins & Minerals
Mask unpleasant flavors
Improve stability & shelf life
Spray Drying
• The flavor or ingredient to be encapsulated is added to the carrier and homogenized to create small droplets in a typical carrier: flavor ratio of 4:1.
• The resultant emulsion is fed into the spray dryer where it is atomized through a nozzle or spinning wheel.
• Hot air contacts the atomized droplets, causing the solvent to evaporate, leaving dried particles.
• Collected through a cyclonic air stream or a bag filter.
• It is immensely suitable for the continuous manufacture of dry solids as either powder, granulates or agglomerates from liquid feeds.
Advantages:
Versatile
Good control
FluidityParticle sizeRedissolution rateBulk densityMechanical strength
Centrifugal Extrusion
• Liquid co-extrusion process utilizing nozzles consisting of concentric orifices located on the outer circumference of a rotating cylinder.
• Liquid core material inner orifice• Liquid wall material outer orifice• Unbroken rope of core material surrounded by wall material• As the device rotates, the rope naturally splits into round droplets
directly after clearing the nozzle.• Walls of the droplets are solidified by cooling or gelling bath capsules• Capsule size (~500 microns) rotational speed• Typical wall materials include starch, maltodextrins, gelatin,
polyethylene glycol• Mostly used to encapsulate flavor oils
Vibrational Nozzle(Annular Jet)
• Core-shell encapsulation can be done using a laminar flow through a nozzle and an additional vibration of the nozzle or liquid.
• Two concentric jets• Rayleigh instability• Very uniform droplets• Lower microcapsule sizes
1. Characterized by wall formation via the rapid polymerization of monomers at the surface of the droplets or particles of dispersed core material.
2. A multifunctional monomer is dissolved in the core material, and this solution is dispersed in an aqueous phase.
3. A reactant to the monomer is added to the aqueous phase, and polymerization quickly ensues at the surfaces of the core droplets, forming the capsule walls.
INTERFACIAL POLYMERZATION
Dynamics• Interfacial polymerization can be used to prepare bigger microcapsules, but
most commercial processes produce smaller capsules in the 20-30 micron diameter range.
• The permeability and size of these microcapsules and the properties of the polymer matrix can be tuned by varying the identity of the monomers/oligomers, the presence of additives and the specific reacting conditions used in the encapsulation such as temperature, concentration or pH.
• Advantages: Rapid, uniform in size products.• Setbacks: Fragility of capsule, lack of biodegradability, excessive drug
degradation.
STEP 1The polymer is dissolved in a water immiscible volatile organic solvent like dichloromethane or chloroform, into which the core material is also dissolved.STEP 2 The resulting solution is added dropwise to a stirring aqueous solution having a suitable stabilizer like poly (vinyl alcohol) to form small polymer droplets containing encapsulated material. STEP 3Droplets hardened to produce the corresponding polymer microcapsules. This hardening process is accomplished by the removal of the solvent from the polymer droplets either by solvent evaporation (by heat or reduced pressure),or by solvent extraction.
SOLVENT EVAPORATION
Polymer+ Volatile organic solvent
Organic Polymeric Phase
Formation of Oil-in-Water
Emulsion
Solvent Evaporation
Particle Formation by Polymer
Precipitation
RECOVERY OF POLYMERIC
MICROPARTICLES
Temperature increase
Active Ingredient
Addition into an aqueousphase (+o/w stabilizer)
• Normal polymerization,can produce microcapsules in the nanometer range.Has the following types
• Bulk polymerization• Suspension polymerization• Emulsion polymerization• Micelle polymerization
IN SITU POLYMERIZATION
• In an emulsion polymerization,surfactant, is dissolved in water until the critical micelle concentration (CMC) is reached. The interior of the micelle provides the site necessary for polymerization. A monomer (like styrene or methyl methacrylate) and a water soluble free radical initiator are added and the whole batch is shaken or stirred.
• This forms a latex• The polymerisation begins and initially produced polymer molecules precipitate in
the aqueous medium to form primary nuclei. As the polymerization proceeds, these nuclei grow gradually and simultaneously entrap the core material to form the final microcapsules
Emulsion polymerization
• A liposome is a tiny vesicle generally made from phospholipids
• They are spontaneously formed when phospholipids are disrupted in water
• Their diameter ranges from 25nm to 10microns.
• Both hydrophobic and hydrophilic active ingredients can be entrapped.
LIPOSOMES
Coacervare :A coacervate is a tiny spherical droplet of assorted organic molecules (specifically, lipid molecules) which is held together by hydrophobic forces from a surround in
liquid.Coacervates measure 1 to 100 micrometers across. Complex coacervation refers to the phase separation of a liquid precipitate, or phase, when solutions of two hydrophilic colloids are mixed under suitable conditions
PolymericMembrane
DropletsHomogeneousPolymer Solution
CoacervateDroplets
PHASE
SEPARATION
MEMBRANE
FORMATION
COACERVATION
MARKET DRIVERS FOR M.E
TECHNOLOGY IN FOOD INDUSTRY
Ingredient Stabilization of processed Food.
Reduced Amount of effort for same effect.
New Product Development
Drive For Brand Differentiation
Celeriac Growth in Functional Food Market
MICRO ENCAPSULATION : BAKERY DELIGHT !
MOLD CONTROL
RAWPRESERVATIVES &
ACIDULANTS
YEAST DESTRUCTION
COSTLY
SORBIC
ACID ENCAPSULATE IN MICROFILM OF VEGE OIL
CONTROLLRED RELEASE
AFTER YEAST ACTIVITY AT
60 C
Encapsulation of Acid PreservativesPromotes Optimal Yeast Activity
Raw Preservatives
Encapsulated Preservatives
CHEMICAL LEAVENING
Sodium Bicarbonate + Acid(s) CO2 + Salt + Water
Inhibition of premature
interactions between ingredients.
Manipulated product attributes.
Provides Freeze thaw stability.
SWEETY PIE
Warm industry milieu causes the sugary solution for confectionery to become sticky. Sugar complexes are encapsulated with a thin film that resist extreme moisture uptake
Un-Cap
MICRO-ENCAPSULATION:“IRON FORTIFICATION IN MILK”
Raw iron catalyzes the oxidation of fats, amino acids and vitamins present in Dairy products. Vit C promotes absorption of Iron by forming a chellate with ferric iron at low pH.
Capsule Core : FeNH4(SO4)24H2O + ascorbic acid
Capsule Coat : Polygylcerol monostearate
Conditioned Release at 37 C
Meat Industry :A FUTILE COMBAT !
Metal salts like Calcium Lactate are widely used for storing meat products and rendering inhibition to animalcule.
Encapsulated Calcium Lactate provides control of calcium-protein aggregates that form when calcium interacts with proteins present in meat.
Heat + Time
To obtain maximum therapeutic efficacy, drug is to be delivered:• to the target tissue• in the optimal amount• in the right period of time • there by causing little toxicity and minimal side effects
One such approach is using microspheres as carriers for drugs.
Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers
Solid biodegradable microspheres
Particle size less than 200 μm.
Reliable means to deliver the drug to the target site with specificity, if modified, and to maintain the desired concentration at the site of interest without untoward effects.
Microspheres received much attention not only for prolonged release, but also for targeting of anticancer drugs to the tumour.
REASONS FOR MICROENCAPSULATION
• Retarding evaporation of a volatile active ingredient.• Improving the handling properties of a sticky material• Isolating a reactive core from chemical attack• For controlled release of drugs• Masking the taste or odor of the AI • For safe handling of the toxic materials• To get targeted release of the drug• Converting liquid into solid form • Isolation of AI from its surroundings, as in isolating vitamins from the deteriorating effects of
oxygen
Preparation of microspheres should satisfy certain criteria:
• The ability to incorporate reasonably high concentrations of the drug.
• Stability of preparation af`ter synthesis with a clinically acceptable shelf life
• Controlled particle size and dispersability in aqueous vehicles for injection
• Release of active reagent with a good control over a wide time scale
• Biocompatibility with a controllable biodegradability
• Susceptibility to chemical modification
Fundamental Considerations
• nature of the core and coating materials. • the microencapsulation methods• the stability and release characteristics of the coated materials.
Composition of Core Material
The core material is defined as the specific material to be coated (a biologically active substance)
The core material can be in liquid or solid in nature.
The composition of the core material can be varied as
Liquid core can include dispersed and/or dissolved material.
Solid core can be single solid substance or mixture of active constituents, stabilizers, diluents, excipients and release-rate retardants or accelerators.
Coating Material
The selection of coating material decides the physical and chemical properties of microcapsules/microspheres.
While selecting a polymer the product requirements should be taken into consideration are:• stabilization • reduced volatility • control release characteristics under specific conditions. • environmental conditions, etc
The polymer should be capable of forming a film that is cohesive with the core material.
It should be chemically compatible, non-reactive with the core material.
It should provide the desired coating properties such as:• strength and stability• flexibility, • Impermeability• Non-hygroscopic, no high viscosity, economical
Generally hydrophilic / hydrophobic polymers /a combination of both are used for microencapsulation process.
Gelatin polyvinyl alcohol ethyl cellulose cellulose acetate phthalate etc are used.
The film thickness can be varied considerably depending on:
the surface area of the material to be coated
Other physical characteristics of the system
Morphology of Microcapsules
The morphology of microcapsules depends mainly on the• Core• Coating Material
Mononuclear (core-shell) microcapsules contain the shell around the core.
Polynuclear capsules have many cores enclosed within the shell.
Matrix encapsulation in which the core material is distributed homogeneously into the shell material.
The microcapsules may consist of a single particle or clusters of particles.After isolation from the liquid manufacturing vehicle and drying, the material appears as a free flowing powder.
The powder is suitable for formulation as:• compressed tablets• hard gelatin capsules• suspensions and other dosage forms.
Release Mechanisms
Mechanisms of drug release from microspheres are
• Degradation controlled monolithic system • Diffusion controlled monolithic system • Diffusion controlled reservoir system• Erosion
Microencapsulation of Aspirin
Materials:-
Aspirin, Acetone, Cyclohexane, Ethanol, Heavy liquid paraffin, ethyl cellulose, and water.
Method
Microcapsules of ethyl cellulose containing aspirin, prepared by an emulsion solvent evaporation method.
Aspirin microcapsules, prepared by dissolving polymers in an organic solvent to form a homogeneous polymer solution.
Addition of core material, aspirin in a thin stream of heavy liquid paraffin.
Agitation using a propeller mixer with the rotation speed 600 rpm.
The dispersed phase consisting of drug and polymer EC immediately transforms into fine droplets, which subsequently solidified into rigid microcapsules due to solvent evaporation.
The liquid paraffin is decant, and the microcapsules are collected, washed twice in cyclohexane to remove any adhering oily phase (liquid paraffin), and are air dried for at least 12h to obtain discrete microcapsules.
Formulation Drug: Polymer Liquid paraffin (ml)
Ethanol (ml)
Ethyl cellulose (gm)
Aspirin :EC 4:1 60 10 1
• prolongs the drug release from dosage forms • reduces adverse effects. • Sustained release formulation of Aspirin reduced the undesired side effects, frequency of administration and
improves patient compliance.
Applications of microencapsulation
• To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc. • Many drugs have been microencapsulated to reduce toxicity and GI irritation including ferrous sulphate and KCl• Alteration in site of absorption can also be achieved by microencapsulation. • Sustained release Aspirin preparations have been reported to cause significantly less G.I. bleeding than
conventional preparations. • A liquid can be converted to a pseudo-solid for easy handling and storage. eg. Eprazinone. • Hygroscopic properties of core materials may be reduced by microencapsulation eg. Sodium chloride. • Carbon tetra chlorides and a number of other substances e.g. . methyl salicylate and peppermint oil have been
microencapsulated to reduce their odor and volatility. • Microencapsulation has been employed to provide protection to the core materials against atmospheric effects
and has enhanced its stability. e.g. vitamin A palmitate. • Separation of incompatible substance has been achieved by encapsulation. • Drug delivery: Controlled release delivery systems• The drugs, which are sensitive to oxygen, moisture or light, can be stabilized by microencapsulation.