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Presented by: SAMIKSHA SAWANT M.Pharm (IP) 2nd SemGuided by: Dr. (Mrs.) INDIRA PARAB

MICROENCAPSULATION AND PARTICLE COATING

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History

Mr. Green made first gelatin microcapsules in 1940

It then took 9 years of research to make available marketed products

Technique of microencapsulation is adapted from nature itself

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What is microencapsulation?

Microencapsulation is a process by which individual particles or droplets of an active material are isolated by being surrounded with a coating to produce a microcapsule.

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Advantages of microencapsulatio

n

sustained/prolonged

drug releaseTaste/odour

masking

Stabilization to drugs

Preventing incompatibilit

y

Free flowing powder

form

Reduce toxicity/ GI irritation

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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.Solid biodegradable microspheres have the

potential throughout the particle matrix for the controlled release of drug.

Microspheres received much attention not only for prolonged release, but also for targeting of

anticancer drugs to the tumour.The size, surface charge and surface

hydrophilicity of microspheres have been found to be important in determining the fate of

particles in vivo.

Studies on the macrophage uptake of microspheres have demonstrated their

potential in targeting drugs to pathogens residing intracellularly

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It is an expensive process

Requires skill

Difficult to obtain continuous and uniform film

Disadvantages

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Formulation considerations• The solid core can be mixture of active

constituents, stabilizers, diluents, excipients and release-rate retardants or accelerators.

Core materials

• Compatible, non reactive with core material

• Provide desired coating properties like strength, flexibility, impermeability, optical properties, non hygroscopicity, tasteless and stable

Coating materials

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Water soluble resins – Gelatin, Gum Arabic,

Starch, Polyvinylpyrrolidone,

Carboxymethylcellulose,

Hydroxyethylcellulose, Methylcellulose,

Arabinogalactan, PVA etc.

Water insoluble resins – Ethylcellulose, Polyethylene,

Polymethacrylate, Polyamide (Nylon), Poly

(Ethylene Vinyl acetate),cellulose

nitrate, Silicones, etc.

Waxes and lipids – Paraffin, Carnauba,

Spermaceti, Beeswax, Stearic acid, Stearyl

alcohol, Glyceryl stearates.

Enteric resins – Shellac, Cellulose acetate phthalate, Zein.

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MICROENCAP-SULATION

TECHNIQUES

Chemical processes:

PolymerizationPolycondensation

Solvent evaporation

Physico-chemical processes:Coacervation

Supercritical CO2 assisted microencapsulationAnti gas solvency

Partial gas saturated solution

Physico-mechanical processes:

Spray drying and congealing

Air suspensionSpinning disc

technique jet cutter Vibrational nozzle

Extrusion technique

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Polymerization

A relatively new microencapsulation method utilizes polymerization techniques to form protective

microcapsule

The methods involve the reaction of monomeric units located at the interface

existing between a core material substance and a continuous phase in

which the core material is dispersed.

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Interfacial polymerisation

In- situ polymerisation

The multifunctional monomer dissolved in liquid core material which will be then dispersed in aqueous phase containing dispersing agent.

A co reactant multifunctional amine will be added to the mixture.

This results in rapid polymerization at interface and generation of capsule shell takes place.

A polyurea shell will be formed when isocyanate reacts with amine,

polynylon or polyamide shell will be formed when acid chloride reacts with amine.

In this process no reactive agents are added to the core material.

polymerization occurs exclusively in the continuous phase and on the continuous phase side of the interface formed by the dispersed core material and continuous phase.

Initially a low molecular weight prepolymer will be formed, as time goes on the prepolymer grows in size.

it deposits on the surface of the dispersed core material thereby generating solid capsule shell.

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PolymerizationSingle emulsion method

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Double emulsion method

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Solvent evaporation The process involves dissolving microcapsule coating

(polymer) in a volatile solvent A core material (drug) to be microencapsulated is

dissolved or dispersed in the coating polymer solution. With agitation, the core – coating material mixture is

dispersed in the liquid manufacturing vehicle phase to obtain appropriate size microcapsules.

Agitation of system is continued until the solvent partitions into the aqueous phase and is removed by evaporation.

This process results in hardened microspheres which contain the active moiety.

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Solvent evaporation

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Coacervation

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Pan coatingSuitable for large particles of size

greater than 600 microns.The particles are tumbled in a pan or

other device while the coating material is applied slowly

The coating is applied as a solution or as an atomized spray to the desired solid core material in the coating pan

Usually, to remove the coating solvent, warm air is passed over the coated materials as the coatings are being applied in the coating pans.

In some cases, final solvent removal is accomplished in drying oven.

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Air suspension technique• In this, the fine core

materials are suspended in a vertical current of air and sprayed with the coating material

• After evaporation of solvent, a layer of encapsulating material is deposited on core

• Gives improved control and flexibility as compared to pan coating

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Rapid expansion of Supercritical fluid

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Anti gas solvency Mix core and shell materials a

solvent which is miscible in supercritical fluid

Now add this to supercritical fluid at high pressure and agitation

This leads to super saturation such that precipitation of the solute occurs . Thus, the solute must be soluble in the liquid solvent, but should not dissolve in the mixture of solvent and supercritical fluid

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Particles from a gas-saturated solution • This process is carried out by mixing core and

shell materials in supercritical fluid at high pressure.

• During this process supercritical fluid penetrates the shell material, causing swelling.

• When the mixture is heated above the glass transition temperature the polymer liquefies.

• Upon releasing the pressure, the shell material is allowed to deposit onto the active ingredient.

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Spray drying and congealingDispersing the core material in a liquefied coating Substance /spraying or introducing the coating mixture on to core material.Coating solidification in spray drying is effected by rapid evaporation of a solvent in which the coating material is dissolved. Coating solidification in spray congealing method is accomplished by thermally congealing a molten coating material or by solidifying a dissolved coating by introducing the coating core material mixture into a non-solvent.

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Spinning disc methodSuspensions of core particles in liquid shell material are poured into a rotating disc.Due to the spinning action of the disc, the core particles become coated with the shell material.The coated particles are then cast from the edge of the disc by centrifugal force.After that the shell material is solidified by external means (usually cooling).This technology is rapid, cost-effective, relatively simple and has high production efficiencies.

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Vibration technologyThis is based on Rayleigh instability

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

To guarantee production of uniform beads and to avoid large size distributions due to coalescence effects during the flight, the droplets pass through an electrostatic field to be charged

As a result these droplets do not hit each other during the flight

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Jet cutter technology• This is a simple technology for bead production that

meets the requirement of producing monodisperse beads originating from low up to viscous fluids with a high throughput

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Particle size

Capture efficiency

Density and bulk density

Viscosity of

polymeric solution

Angle of repose

Polymer solubility

in solvents

In vitro methods

Morphology

CHARACTERIZATION

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Applications Microencapsulation has been employed to provide

protection to the core materials against atmospheric effects, e.g., Vitamin A Palmitate.

Separation of incompatible substance has been achieved by encapsulation

To mask the bitter taste of drugs like Paracetamol, Nitrofurantoin etc.

To reduce gastric and other gastro intestinal (G.I) tract irritations, For eg, sustained release Aspirin preparations have been reported to cause significantly less G.I. bleeding than conventional preparations.

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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 e.g. Sodium chloride.

Carbon tetra chlorides and a number of other substances have been microencapsulated to reduce their odour and volatility

To reduce volatality of liquids like peppermint oil Helps to prepare SRDF and enteric coated products,

controlled release products Used to improve flow properties before compression

into tablets

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INJECTABLES:Smaller molecules can stay in the blood stream

longer with fewer side effectsLess frequent injectionMore sophisticated site targettingDecreased toxicity

BIOLOGICS:The harsh condition in the stomach denatures most

proteins and peptides hence they require some sort of depot or extended release can be done by microencapsulation.

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After hydrolysis in in the lower intestine, the polyunsaturated fats is digested and absorbed, thereby resulting in higher amounts of unsaturated fats in milk

and meat.

Polyunsaturated vegetable oil was encapsulated in protein core and reacted with formaldehyde, thus protecting the unsaturated fats from bacteria in

rumen.

Plant fat contains polyunsaturated fatty acids, but milk and meat contains only 2-4% of it

MICROENCAPSULATION FOR DECREASING ATHEROSCLEROSIS

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Recent studies• Hughes provided a method of sustained delivery of an

active drug to a posterior part of an eye of a mammal to treat or prevent a disease or condition affecting mammals. The method is comprised of administering an effective amount of an ester prodrug of the active drug such as tazarotene (prodrug of tazarotenic acid) subconjunctivally or periocularly since a systemic administration requires high systemic concentration of the prodrug. The ester prodrug is contained in biodegradable polymeric microparticle system prepared using the o/w emulsion solvent evaporation methods.

• Encapsulation of nucleotides and growth hormone using simple or double emulsification methods was achieved by Johnson et al

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• A method of encapsulating DNA retaining its ability to induce expression of its coding sequence in a microparticle for oral administration prepared using the w/o/w emulsion and using biodegradable polymers under reduced shear is produced by Jones et al

• Reslow et al. utilized starch to encapsulate vaccines using emulsification method. In process, an immunologically active substance (vaccine) is suspended in an aqueous starch solution with an amylopectin content exceeding 85% by weight. The starch droplets containing the vaccine are allowed to gel as the starch has capacity to gel naturally.

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Brand name API Manufacturer

OROS CT(osmotically active

tablets)

Colon specific drugs Alza corp.

ReGel(oncogel)

Paclitaxel Macro Med Inc.

Clopigrel clopidogrel+ Aspirin Lupin pinnacle

Clobitab clopidogrel+ Aspirin Lupin pinnacle

Atoplus Atorvastatin Triton (calyx)

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References• The Theory and Practice of Industrial Pharmacy,

lachman/lieberman, 4th edition, pg no. 579-596• Microencapsulation- Processes and Applications,

edited by Tan E. Vandegar, pg no. 1-20 and 57-59• Multiparticulate drug delivery, edited by Iisaac

Ghebre- Sellassie, pg no. 51-109• The Design and Manufacture of Medicines,

Michael Aulton and Kevin M.G.Taylor, 4th edition, pg no. 578-581

• Polymeric Drug Delivery- Particulate Drug Carriers, edited by Sonke Svenson, pg no. 242-245

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References• Microencapsulation: a vital technique in novel drug delivery system

P.Venkatesan, R.Manavalan and K.Valliappan (http://jpsr.pharmainfo.in/Documents/Volumes/Vol1Issue4/

jpsr01040903.pdf)• Microencapsulation: Process, Techniques and Applications Hammad

umer*1 , Hemlata Nigam2 , Asif M Tamboli2 , M. Sundara Moorthi Nainar2

(http://www.ijrpbsonline.com/files/R017.pdf) • Microencapsulation: a review jyothi sri.s* 1 , a.seethadevi 1 , k.suria

prabha 1 , p.muthuprasanna 1 and ,p.pavitra2 (http://ijpbs.net/vol-3/issue-1/bio/P%20-%2058.pdf)• Microencapsulation – A Novel Approach in Drug Delivery: A Review Nitika Agnihotri, Ravinesh Mishra*, Chirag Goda, Manu Arora (file:///C:/Users/B%20A%20Sawant/Downloads/IGPS_2_1.-Nitika-

Agnihotri-et-al-2012.pdf)

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References

• Reslow M, Bjorn S, Drustrup J, Gustafsson NO, Jonsson M, Laakso T, inventors. A controlled release, parenterally administrable microparticle preparation. EP1328258. 2008

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093624/)

• Microencapsulation(https://uqu.edu.sa/files2/tiny_mce/plugins/

filemanager/files/4290121/MICROENCAPSULATION.pdf

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Thankyou