microsphere shm
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M I c r o s p h e r e SM I c r o s p h e r e S
Microspheres & Microcapsules
A MicrocapsuleMicrocapsule has a drug located centrally within the particle, where it is encased within a unique polymeric membrane
A MicrosphereMicrosphere has its drug dispersed throughout the particle i.e. the internal structure is a matrix of drug and polymeric excipients
Microencapsulation
• Microencapsulation is a process by which solids, liquids or even gases may be enclosed in microscopic particles formation of thin coatings of wall material around the substances.
• The process had its origin in the late 1930s as a cleaner substitute for carbon paper & carbon ribbons as sought by the business machines industry.
• The ultimate development in the 1950s of reproduction paper & ribbons that contained dyes in tiny gelatin capsules released on impact by a typewriter key or the pressure of a pen or pencil was the stimulus for the development of a host of microencapsulated materials, including drugs.
• The first research leading to the development of microencapsulation procedures for the Pharmaceuticals was published by Bungen burg de Jong and Kan in 1931 & dealt with the preparation of gelatin spheres & the use of a gelatin Coacervation process.
• Microspheres are characteristically free flowing powders consisting of protiens or synthetic polymers which are biodegradable in nature and ideally having particle size less than 200 μm.
Reasons for Microencapsulation
• Production of novel product• Protection of the product from the surrounding environment,
hence improving the shelf life of the product and stability of the system
• Protection of environment from product, where active core material is hazardous or toxic
• Separation of components, allowing control of incompatibility of components
• Control rate of release of core material, by rupture of polymer wall e.g. by impact or long acting sustained release e.g. solution or diffusion
• Masking undesired properties of active component e.g. odour, taste
• Formation of solid systems e.g. conversion of liquid components to free flowing powders
• Targeting of site of release of active material
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Applications of microencapsulation• Sustained drug delivery
• Prolonged action medications
• Taste masked chewable tablets.
• Powders and suspensions.
• Single layer tablet containing chemically incompatible ingredients.
• New formulation concepts of creams, ointments, aerosols, dressings, plasters, suppositories and injectables.
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Disadvantages of microencapsulation
• No single microencapsulation technique is adaptable to core
material.
• Incomplete or discontinuous coating.
• Non reproducible and unstable release characteristics.
• Non economic method.
• At present, there is no universally accepted size range that particles
must have in order to be classified as microcapsules.
• Many researchers classify capsules smaller than 1 um as
nanocapsules and capsules larger than 1000 um as macrocapsules.
• Commercial microcapsules typically have a diameter between 3 and
800 um and contain 10-90 wt. percent core.
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Core material
• It is defined as specific material to be coated.
• It can be liquid or solid.
• Composition of core material is varied
Liquids: dispersed and/or dissolved materials.
Solids: mixture of active constituents, stabilizers,
diluents, release rate retardants or accelerators etc..
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Core material
Core materialCore material Characteristic Characteristic propertyproperty
PurposePurpose Dosage formDosage form
Acetaminophen Acetaminophen Slightly water Slightly water solublesoluble
Taste maskingTaste masking TabletTablet
Activated Activated charcoalcharcoal
AdsorbentAdsorbent Selective sorptionSelective sorption Dry powderDry powder
AspirinAspirin Slightly water Slightly water solublesoluble
Taste masking, Taste masking, SR, reduced SR, reduced gastric irritationgastric irritation
Tablet or Tablet or capsulecapsule
Isosorbide Isosorbide dinitratedinitrate
Water soluble Water soluble solidsolid
SRSR CapsulesCapsules
Potassium Potassium chloridechloride
Highly water Highly water solublesoluble
Reduced gastric Reduced gastric irritationirritation
CapsulesCapsules
Vitamin A Vitamin A palmitatepalmitate
Non volatile liquidNon volatile liquid Stabilization to Stabilization to oxidationoxidation
Dry powderDry powder
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Coating material
• It can be defined as material which coat the core material.
• Before selecting coating material following criteria are to be evaluated.
Specific dosage or product requirement- stabilization, reduced volatility, release characteristics, environmental condition etc…
Which material will satisfy product objectives and requirements.
Which encapsulation method is best suited
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Microencapsulation techniques• Air suspension
• Coacervation phase sepeartion
• Multiorifice centrifugal
• Pan coating
• Solvent evaporation
• Spray drying and congealing.
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Microspheres Preparation
Homogenization
W/O emulsion
Stirring
Centrifuge andWashing with D.W.Freeze Drying
Solvent evaporation or solvent extraction
W1+O
Microspheres
W2
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Microencapsulation Microencapsulation processprocess
Applicable core Applicable core materialmaterial
Approx particle size Approx particle size (um)(um)
Air suspensionAir suspension SolidsSolids 35-500035-5000
Coacervation phase Coacervation phase seperationseperation
Solids and liquidSolids and liquid 2-50002-5000
Multiorifice centrifugalMultiorifice centrifugal Solids and liquidSolids and liquid 1-50001-5000
Pan coatingPan coating SolidsSolids 600-5000600-5000
Solvent evaporationSolvent evaporation Solids and liquidsSolids and liquids 5-50005-5000
Spray drying and Spray drying and congealingcongealing
Solids and liquidsSolids and liquids 600600
Preparation of Microspheres
Should satisfy certain criteria
1. The ability to incorporate reasonably high concentrations of drug
2. Stability of the preparation after synthesis with a clinically
acceptable shelf-life
3. Controllable particle size & dispersability in aqueous vehicles for
vehicles for injection
4. Release of active agent with good control over a wide time scale
5. Biocompatibility with a controllable biodegradability
6. Susceptibility to chemical modification
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Method of drug incorporation
Drugs are incorporated into the microspheres either During their synthesis or After the microspheres are formed.
High loading can be achieved by in situ loading if the drug is insoluble in the dispersion medium
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Drug-polymer binding
The binding force that holds the drug to the microsphere
matrix can either be physical or chemical.
Hydrophobic & electrostatic incorporation may also exist.
Drug release from matrix depends on these forces.
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Routes of Administration
Oral
Parenteral
Others
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Fate of microspheres in Fate of microspheres in bodybody
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Mechanism of Drug Mechanism of Drug releaserelease
Degradation controlled monolithic system
Diffusion controlled monolithic system
Diffusion controlled reservoir system
Erodable polyagent system
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Targeting of microspheres Targeting of microspheres
Passive targeting
Active targeting
Targeting using magnetic microspheres
Intracellular targeting
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Microspheres based on Natural Microspheres based on Natural PolymerPolymer
Albumin microspheres
Casein microspheres
Gelatin microspheres
Polysaccharide microspheres
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Microspheres of synthetic Microspheres of synthetic biodegradable polymerbiodegradable polymer
Polyester microspheres
Polyanhydride microspheres
Other biodegradable polymers (Poly ortho esters, polyhydroxy
butyrate, etc)
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Evaluation of microspheres• Physical characterization: bulk density, true density, tapped
density, hausners index, compressibility index
• Particle size determination – optical microscopy, electric methods.
• % encapsulation efficiency – gives idea about the drug content.
• Assay- depicts amount of drug present .
• Surface characteristics: SEM (Scanning electron Microscopy)
• Drug release study- dissolution apparatus type I basket type.
• Stability studies
ReferencesReferences
• Birnbaum D. T, Peppas L.B., “Microparticle Drug Delivery Systems”, Available on
www.bme.utexas.edu/faculty/.../BrannonPeppas.LBPCancerChapter2003.pdf
• Venkatesan P. et al, »Microencapsulation: A Vital Technique in Novel Drug
Delivery System”, J. Pharm. Sci. & Res. Vol.1(4), 2009, 26-35.
• N.K. Jain, “Controlled & Novel Drug Delivery”, CBS Publisher & distributor, 237-250.
• Vyas S.P., Khar R. K., “Targetted & controlled drug delivery”, CBS Publisher &
distributors, 417-457.
• Trivedi P., Verma A. M. L., Garud N., “Preparation & characterisation of aceclofenac
microspheres”, Asian Journal of Pharmaceutics, Apr 2008, 110-115.
• Dey N.S., Majumdar S, Rao M.E.B., “Multiparticulate Drug Delivery Systems for
Controlled Release”, Tropical Journal of Pharmaceutical Research, September
2008; 7 (3): 1067-1075.23
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