SEMINAR BY: B.

THILAK CHANDRA
M.PHARMACY(PHARMACEUTICS),(II-Semester) VAAGDEVI INSTITUTE OF PHARMACEUTICAL SCIENCES BOLLIKUNTA, HANAMKONDA.

CONTENTS

INTRODUCTION CLASSIFICATION OF POLYMERS. METHODS OF PREPARATION. MECHANISAM OF DRUG RELEASE FROM MICROSPHERE. CHARACTERIZATION. APPLICATIONS. CONCLUSION. REFERENCES

INTRODUCTION
Definition of microspheres Microparticles or microspheres are defined as small spheres made of any material and sized from about 50 nm to about 2 mm.
The term nanospheres is often applied to the smaller spheres (sized 10 to 500 nm) to distinguish them from larger microspheres
Microbeads and beads are used alternatively for microspheres.

 Ideally, microspheres are completely spherical and homogeneous in size.

Types of Microspheres
Microcapsule: consisting of an encapsulated core particle. Entrapped substance completely surrounded by

a distinct capsule wall.

Types of Microspheres

Microcapsule

Micromatrix

Micromatrix: Consisting of homogenous dispersion of active ingredient in particle.

Polymers used in the Microsphere preparation

Synthetic Polymers Non-biodegradable PMMA Acrolein Epoxy polymers
Biodegradable Lactides and Glycolides copolymers Polyalkyl cyanoacrylates Polyanhydrides

 Natural Materials

Proteins
Albumins Gelatin Collagen

Carbohydrates
Starch agarose Carrageenan Chitosan

Chemically modified carbohydrates

Poly(acryl)dextran Poly(acryl)starch

GENERAL METHODS OF PREPARATION

Single Emulsion techniques Double emulsion techniques Polymerization techniques

- Normal polymerization. - Interfacial polymerization Coacervation phase separation techniques Spray drying and spray congealing Solvent extraction

SIMPLE EMULSION BASED METHOD

Aq.Solution/suspension of polymer
Stirring, Sonication

Dispersion in organic phase (Oil/Chloroform)

Heat denaturation
CROSS LINKING

Chemical cross linking (Glutaraldehyde/For maldehyde/Butanol

Microspheres in organic phase

Microspheres in organic phase Centrifugation, Washing, Separation

MICROSPHERES

DOUBLE EMULSION BASED METHOD

Aq.Solution of protein/polymer
Dispersion in oil/organic phase Homogenization

First emulsion (W/O) Addition of aq. Solution of PVA Multiple emulsion

Addition to large aq. Phase Denaturation/hardening

Microspheres in solution

Separation, Washing, Drying

MICROSPHERES

Polymerization techniques

Polymerization techniques
Normal polymerization
Bulk polymeriza -tion Suspension polymerization Emulsion polymerization

Interfacial polymerization

BULK POLYMERIZATION

Monomer bioactive material initiation

Polymerization with heating /initiator

Polymer block
Mould/mechanical fragmentation

microspheres

Suspension polymerization
Monomer, bioactive materials, initiator
Dispersed in water

Droplets
Vigorous agitation Heat/ irradiation

Microspheres

Emulsion polymerization
Monomer/ bioactive material Aq.solution of NaOH with intiator, surfactant above cmc stabilizer

Dispersion with vigorous stirring

Micellar solution of polymer in aq.medium

polymerization

Microspheres formation
Seperation, washing, drying

Microspheres microspheres

Interfacial Polymerization technique

When two reactive monomers are dissolved in immiscible

solvents, the monomers diffuse to the oil- water interface where they react to form a polymeric membrane that envelopes dispersed phase.
Drug is incorporated either by being dissolved in the

polymerization medium or by adsorption onto the nanoparticles after polymerization completed.

The nanoparticle suspension is

then purified to remove various stabilizers and surfactants employed for polymerization by ultracentrifugation and resuspending the particles in an isotonic surfactant-free medium.

PHASE SEPARATION METHOD

Aqueous/Organic.Solution of polymer

Drug
Drug dispersed or dissolved in polymer solution

Polymer rich globules

Hardening
Microspheres in aq./organic phase

Separation, Washing, Drying MICROSPHERES

Salting-out process
An aqueous phase saturated with electrolytes (e.g.,

magnesium acetate, magnesium chloride) and containing PVA as a stabilizing and viscosity increasing agent is added under vigorous stirring to an acetone solution of polymer.
In this system, the miscibility of both phases is prevented

by the saturation of the aqueous phase with electrolytes, according to a salting-out phenomenon.
The addition of the aqueous phase is continued until a

phase inversion occurs and an o/w emulsion is formed

Emulsification-Solvent evaporation method

DRUG LOADING
During the preparation of microspheres or after the formation

of microspheres by incubating.
Loading into preformed microspheres has an advantage of

removing all impurities from microsphere preparation before the drug is incorporated.
High loading can be achieved by insitu loading.

If the drug is insoluble in dispersion medium employed for

microsphere stabilization.

ROUTE OF ADMINISTRATION

ORAL DELIVERY
PARENTERAL DELIVERY

MECHANISM OF DRUG RELEASE

Degradation controlled monolithic system. Diffusion controlled monolithic system. Diffusion controlled reservoir system.

Erodable polyagent system.

Characterisation
PARAMETERS METHODS
Light microscope, scanning electron microscope, confocal laser scanning microscopy . electron spectroscopy for chemical analysis (esca)

1. PARTICLE SIZE AND SHAPE 2. CHEMICAL ANALYSIS

3. DEGRADATION Attenuated total reflectance Fourier TransformInfrared Spectroscopy OF POLYMER MATRIX

4. DENSITY DETERMINAT ION

5. ISOELECTRIC POINT

Multivolume pychnometer

Micro-electrophoresis

PARTICLE SIZE

6. CAPTURE EFFICIENCY

7. RELEASE STUDIES
Rotating paddle apparatus
APPARATUS paddle BUFFER 7.4ph AGITATION 100rpm

Dialysis method

8.

ANGLE OF CONTACT

Determine wetting property of microparticulate carrier.

POTENTIAL USE OF MICROSPHERES IN THE PHARMACEUTICAL INDUSTRY

Taste and odour masking. Conversion of oils and other liquids to solids for ease of handling. Protection of drugs against the environment (moisture, light etc.). Separation of incompatible materials (other drugs or excipients). Improvement of flow of powders. Aid in dispersion of water-insoluble substances in aqueous media, and Production of SR, CR, and targeted medications.

OTHER APPLICATIONS
Microcapsules are also extensively used as diagnostics, for

example, temperature-sensitive microcapsules for thermographic detection of tumors.

In the biotechnology industry microencapsulated microbial

cells are being used for the production of recombinant proteins and peptides.
Encapsulation of microbial cells can also increase the cell-

loading capacity and the rate of production in bioreactors.

A feline breast tumor line, which was difficult to grow in

conventional culture, has been successfully grown in microcapsules.

Microencapsulated activated charcoal has been used for

hemoperfusion.

 Microspheres are made from polymeric , waxy or protective

materials that is biodegradable synthetic polymers and modified natural products.

Solid biodegradable microspheres incorporating a drug

dispersed or dissolved throughout particle matrix have the potential for controlled release of the drug.
These carriers received much attention not only for prolonged

release but also for the targeting anti cancer drugs to the tumour. These Microspheres are free-flowing and roll with practically no friction, that means there is no abrasion, guaranteeing a dust-free environment.

MARKETED PRODUCTS
Drug Risperidone Commercial name RISPERDAL CONSTA Vivitrol Company Janssen/Alker mes, Inc. Alkermes Technology Double emulsion (oil in water) Double emulsion (oil in water) Phase separation Indication Schizophrenia; bipolar I disorder Alcohol dependence Acromegaly

Naltrexone

Octreotide

Sandostatin LAR

Novartis

Somatropin

Nutropin Depota

Genentech/Alk Alkermes ermes ProLease Technology (Cryogenic spray-drying)

Novartis Orapharma Spray dry

Growth deficiencies

Bromocriptine Minocycline

Parlodel LAR Arestin

Parkinsonism Periodontitis

CONCLUSION
The concept of microsphere drug delivery systems offers certain advantages over the conventional drug delivery systems such as controlled and sustained delivery. Apart from that microspheres also allow drug targeting to various systems such

as ocular , intranasal , oral and IV route . Novel technologies like magnetic microspheres, immunomicrospheres offer great advantages and uses than conventional technologies.

Further more in future by combining various other strategies, microspheres will find the central place in novel drug delivery,

particularly in diseased cellsorting ,diagnostics, gene and genetic materials, safe,targated and effective invivo delivery which may have implications in gene therapy.
This area of novel drug delivery has innumerable applications and there is a need for more research to be done in this area.

REFERENCES
International Journal for Targeted & Controlled Drug

Delivery Novel Carrier Systems., S.P.Vyas., R.K.Khar, First Edition :2002.,Reprint :2007 page no:417,453. Review: Radioactive Microspheres for Medical Applications. International journal of Pharmaceutics 282 (2004) 118,Review polymer microspheres for controlled drug release. Controlled and novel drug delivery edited by N.K.Jain reprint 2007 pg.no.236-255. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811640.

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