MIcrosphereS

Microspheres & Microcapsules

A Microcapsule has a drug located centrally within the particle, where it is encased within a unique polymeric membrane A Microsphere 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 m.

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

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.
5

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
6

Core material
It is defined as specific material to be coated. It can be liquid or solid. Composition of core material is varied p Liquids: dispersed and/or dissolved materials. p Solids: mixture of active constituents, stabilizers, diluents, release rate retardants or accelerators etc..

Core material
Core material Acetaminophen Characteristic property Slightly water soluble Purpose Taste masking Selective sorption Dosage form Tablet Dry powder

Activated charcoal Adsorbent Aspirin Slightly water soluble

Taste masking, SR, Tablet or capsule reduced gastric irritation Capsules Capsules Dry powder
8

Isosorbide dinitrate Water soluble solid SR Potassium chloride Highly water soluble Reduced gastric irritation Vitamin A palmitate Non volatile liquid Stabilization to oxidation

Coating material
It can be defined as material which coat the core material. Before selecting coating material following criteria are to be evaluated. p Specific dosage or product requirement- stabilization, reduced volatility, release characteristics, environmental condition etc p Which material will satisfy product objectives and requirements. p Which encapsulation method is best suited
9

Microencapsulation techniques
Air suspension Coacervation phase sepeartion Multiorifice centrifugal Pan coating Solvent evaporation Spray drying and congealing.

10

Microspheres Preparation

Homogenization
W1+O W2

Stirring

W/O emulsion

Solvent evaporation or solvent extraction Centrifuge and Freeze Drying Washing with D.W.

Microspheres

11

Microencapsulation process Air suspension

Applicable core material Approx particle size (um) Solids 35-5000

Coacervation phase seperation Multiorifice centrifugal

Solids and liquid Solids and liquid

2-5000 1-5000

Pan coating Solvent evaporation Spray drying and congealing

Solids Solids and liquids Solids and liquids

600-5000 5-5000 600

12

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
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 body

17

Mechanism of Drug release

Degradation controlled monolithic system Diffusion controlled monolithic system Diffusion controlled reservoir system Erodable polyagent system

18

Targeting of microspheres
Passive targeting Active targeting Targeting using magnetic microspheres Intracellular targeting

19

Microspheres based on Natural Polymer

Albumin microspheres Casein microspheres Gelatin microspheres Polysaccharide microspheres

20

Microspheres of synthetic biodegradable polymer

Polyester microspheres Polyanhydride microspheres Other biodegradable polymers (Poly ortho esters, polyhydroxy butyrate, etc)

21

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.

22

References
Birnbaum D. T, Peppas L.B., Microparticle Drug Delivery Systems, Available on www.bme.utexas.edu/faculty/.../BrannonPeppas.LBPCancerChapter2003.p df 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
23

aceclofenac microspheres, Asian Journal of Pharmaceutics, Apr 2008, 110-

24