1

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

5

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.

6

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.

7

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..

8

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

9

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

10

Microencapsulation techniques• Air suspension

• Coacervation phase sepeartion

• Multiorifice centrifugal

• Pan coating

• Solvent evaporation

• Spray drying and congealing.

11

Microspheres Preparation

Homogenization

W/O emulsion

Stirring

Centrifuge andWashing with D.W.Freeze Drying

Solvent evaporation or solvent extraction

W1+O

Microspheres

W2

12

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

13

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

14

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.

15

Routes of Administration

Oral

Parenteral

Others

16

Fate of microspheres in Fate of microspheres in bodybody

17

Mechanism of Drug Mechanism of Drug releaserelease

Degradation controlled monolithic system

Diffusion controlled monolithic system

Diffusion controlled reservoir system

Erodable polyagent system

18

Targeting of microspheres Targeting of microspheres

Passive targeting

Active targeting

Targeting using magnetic microspheres

Intracellular targeting

19

Microspheres based on Natural Microspheres based on Natural PolymerPolymer

Albumin microspheres

Casein microspheres

Gelatin microspheres

Polysaccharide microspheres

20

Microspheres of synthetic Microspheres of synthetic biodegradable polymerbiodegradable polymer

Polyester microspheres

Polyanhydride microspheres

Other biodegradable polymers (Poly ortho esters, polyhydroxy

butyrate, etc)

21

22

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

24