MICROSPHERES &

MAGNETIC MICROSPHERES

PRESENTED BY GUIDED BY

K. Swapna Dr.Yasmin begam

256213886015 M.Pharm, Ph.D

CONTENTS

INTRODUCTION

CONCEPT

ADV AND DISADV

MATERIALS REQUIRED

IDEAL MICROSPHERE PREREQUISITES

METHOD OF PREPARATION

CHARACTERIZATION or EVALUATION

APPLICATIONS

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CONCEPT

The Main Concept involved is :

Accurate Delivery of Small quantities of Potent Drug and

provide Controlled Release. .

Eg : Narcotics , Antagonist and Steroid hormones.

Selective and Effective Localization of pharmacologically active moiety at preselected target(s) in therapeutic concentration,,

Disable it’s Exposure to non-target normal tissues and cells.

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ADVANTAGES :

SC, IM or Intraperitoneal administration

Biodegradable microspheres containing antigens will protect the antigens from the proteolysis

It is inexpensive (Encapsulation method)

Various degrees of controlled release can be achieved

More uniform effect of the drug

Reduction of drug Side Effects

Reduced fluctuation in circulating drug levels

Avoids hepatic first pass metabolism

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DISADVANTAGES :

High molecular weight compounds have limited & restricted loading & their release may be difficult

Formation of complexes with the blood components

High cost

Productivity more difficult

Reduced ability to adjust the dose

Highly sophisticated technology

Requires skills to manufacture

Difficult to maintain stability of dosage form.

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PREREQUISITES FOR IDEAL MICROSPHERES

Longer duration of Action

Control of Content Release

Increased Therapeutic Efficiency

Drug Protection

Reduction of Toxicity

Biocompatibility

Sterilizability

Relative Stability

Dispersability

Targetability

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MATERIALS USED FOR THE PREPARATION

Natural materials Synthetic polymers

Proteins

Eg : Albumins , Gelatin

Non-biodegradable

Eg : Acrolein , Epoxy polymers

Carbohydrates

Eg : Starch , Agarose

Chemically Modified

Carbohydrates

Eg : Poly (Acryl)dextran ,

Poly(Acryl)starch

Biodegradable

Eg : Lactides and glycolides and their

copolymers

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METHOD OF PREPARATION

Single Emulsion Technique

Double Emulsion Technique

Polymerization techniquesNormal polymerization

Interfacial polymerization

Coacervation technique

Spray Drying & Spray Congealing

Solvent Extraction

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SINGLE EMULSION TECHNIQUE

Microparticulate carrier of natural polymers

are dissolved or dispersed in aqueous

medium followed by dispersion

The cross linking can be achieved either by

means of heat or by using the chemical cross

linkers like glutaraldehyde, formaldehyde,

butanol .

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Aq solution/suspension of polymer

Dispersion in org phase oil/chloroform

Microspheres in org phase Microspheres in org phase

Cross linkingHeat/Denaturation Chemical

Micro spheres

Centrifugation, washing, separation

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DOUBLE EMULSION TECHNIQUE

It involves the formation of the multiple emulsion of type w/o/w & is best suited for the water soluble drugs

A number of hydrophilic drugs like LH-RH agonists, vaccines, proteins or peptides & conventional molecules are successfully incorporated in to the microspheres using the method of double emulsion solvent evaporation or extraction

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Aq sol of protein/polymer drug (if present)

Dispersed in Oil

First emulsion

Multiple emulsion

Micro spheres in solution

Micro spheres

Homogenization

Addition of aq sol of PVA

Addition to large aq phase(Denaturation)

Separation, washing, drying

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POLYMERIZATION TECHNIQUES

Normal polymerization

Bulk polymerization,

Suspension precipitation and

Emulsion polymerization

Interfacial polymerization

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BULK POLYMERIZATION

Monomer, Bioactive material, Initiator

Polymer Block

Microspheres

Polymerization

Mould/ mechanical fragmentation

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SUSPENSION POLYMERIZATION

Monomer, Bioactive material, Initiator

Droplets

MICROSPHERES >100µM

Separation & drying

Vigorous agitation, heat

Dispersed in water & stabilizer

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EMULSION POLYMERIZATION

Monomer/ bioactive material Aq sol of NaOH, initiator, surfactant

Micellar sol of polymer in aq medium

Microspheres formation

MICROSPHERES

Separation, washing, drying

polymerisation

Vigorous stirring

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INTERFACIAL POLYMERIZATION

It involves reaction of various monomers at

the interface between the two immiscible

liquid phases to form a film of polymer

The continuous phase is generally aqueous

in nature throughout which the second

monomer is emulsified

The monomers present in either phase

diffuse rapidly & polymerize rapidly at the

interface.

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COACERVATION TECHNIQUE

Aq/ org sol of polymer

Drug dispersed in polymer sol

Polymer rich globules

Microspheres in aq/ org phase

Microspheres

Phase separation

Hardening

Separation, drying

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SPRAY DRYING AND SPRAY CONGEALING

Based on drying of the mist of the polymer and drug in the air

The polymer is first dissolved in a suitable volatile organic solvent

The drug in solid form is then dispersed in polymer solution under high speed homogenization;

It is then atomized in a stream of hot air.

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CONT’D

Formation of the small droplets or fine mist

from which the solvent evaporates

instantaneously leading to formation of the

microspheres

Micro particles are separated from the hot air

by means of the cyclone separator and

traces of solvent are removed by vacuum

drying

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SOLVENT EXTRACTION

Here microspheres are prepared by removal of the organic solvent with extraction with water

This process decreases the hardening time of microspheres

It depends on the temperature of water, ratio of emulsion volume to the water and the solubility profile of the polymer.

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CHARACTERIZATION OF MICROSPHERES

Particle size and shape

Electron spectroscopy for chemical analysis

Attenuated total reflectance Fourier transform-infrared spectroscopy

Density determination

Isoelectric point

Surface carboxylic acid residue

Surface amino acid residue

Capture efficiency

Release studies

Angle of contact

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Capture efficiency

% Entrapment = Actual content X100

Theoretical content

Density Measurement : By Using Multivolume Pychometer

Release Studies : By Two Methods:

a) Rotating Paddle Dissolution Apparatus

b) Dialysis Method

Media : Phosphate Saline Buffer at pH 7.4

Isoelectric Point : By Using Micro electrophoresis

Apparatus

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In vitro drug release studies:

Microspheres of all batches had faster initial drug release approximately 25 percentages within 15 minutes. Then the release was slow and sustained over 8 hours, depending upon the polymer: drug ratio. By the end of 8th hour the percentage of drug release was found to 79.22, 84.72 and 94.12 for F1, F2 and F3 formulation respectively (figure 2). The formulation F3 showed better sustained release (94%) at the end of the 8th hour as compared to other batches. This may be due to better loading, encapsulation efficiency and increased particle size as compared to other batches.

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APPLICATIONS

1] In Vaccine Delivery

2] In Case of Antigen Release

3] Targeting of Drug

4] ImmunoMicrospheres

5] MicroSponges : Topical porous Microspheres

6] Surface Modified Microspheres

7] Imaging

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CONTENTS

1] INTRODUCTION

2] CONCEPT

3] IDEAL CHARACTERISTICS

4] MATERIALS CREATING MF

5] ADVANTAGES AND DISADVANTAGES

6] APPLICATIONS

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INTRODUCTION

DEFINITION :

Magnetic Microspheres (MM):

These are microspheres, containing magneticsubstance inside which, can be easily targeted byapplying external magnetic field.

They were mainly developed to minimize renalclearance and to increase target site specificity. Thissystem has a great potential in the treatment oflocalized tumors in the regions of well-defined bloodsupply.

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CONCEPT

1] Ideally, magnetic microspheres are injected and selectively a

and magnetically localized at the capillary level, they would

have free flow access through the large arteries.

2] The selective capillary localization of the microspheres can be

achieved by taking advantage of the physiological difference in the

linear flow velocity of blood at the capillary level (0.05 cm/sec).

Obviously, a much lower magnetic field strength is necessary to restrict

the microspheres at the slower moving flow velocities of blood in

capillaries.

After removal of the magnetic field, the microspheres stillcontinued to lodge at the target site, presumable because they had lodgedin the vascular endothelium, penetrated in to the interstitial space,resulting in their retention.

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IMPORTANT CHARACTERISTICS

Particle size of a drug carrier can affect the degree of drug entrapment.

Increase in size of albumin microspheres due to hydration can alter its

distribution.

Use of sub micro size microspheres minimizes the incidence of pulmonary

embolism often encounter with particles greater than 7 microns or particles,

which aggregate upon their in vivo administration.

The retention of magnetic microspheres at the target site is dependent on the

magnetic content of the carrier and the magnitude of applied magnetic field.

In targeting, using MM, the magnetic content of the carrier and the magnitude

of applied magnetic field are important.

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Note: Incorporation of drug and magnetic needs to

be delicately balanced. Depending on the

type of drug and the desired target site, the

optimum magnetic content would vary

between 20% and 50% magnetic by dry

weight of the drug carrier complex

retention..

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MAGNETIC FIELD CREATORS MAGNETITE:

It is also called as ferric ferrous oxide, tri iron tetra oxide,and black iron oxide.

Magnetic iron oxide with chemical formula FeOfe203having a molecular weight of 231.55 with a chemicalcomposition of Fe=72.36%, O=27.64%.

The Ferro magnetic material when incorporated intomicrospheres makes them magnetically responsive, so thatthey can be concentrated to the desired site by applying someexternal magnetic field.

OTHER MF CREATORS ARE : ADRIAMYCIN,VINDESIN SULPHATE

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ADVANTAGES :

Incorporation of magnetically responsive materials into microspheresmakes them susceptible to applied magnetic field, so that they areconcentrated to the target site by application of magnetic field externallyto that site. Due to this, rapid clearance of these microspheres by RES isprevented.

Microspheres can transit into extra vascular space creating an extravascular depot of drug for sustained release of drug within the targetedareas.

Increase of tumor targeting microspheres can be internalized by tumorcell due to its much-increased phagocytic activity as compared tonormal cell. So the problem of drug resistance due to inability of drugto be transported across the cell membrane can be prevented.

Controlled and predictable rate of drug release with smaller doses ofdrug can be achieved.

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DISADVANTAGES

One of the major limitations of this system is, the drug cannotbe targeted to deep-seated organism in the body. This approachis confined to the targeting of drugs to the superficial tissueslike skin, superficial tumors or the joints.

Thrombosis at the site of administration.

The unknown toxicity of magnetic beads.

The possible unwanted localization of the product in the liverand the regions of RES and the dangerous effect of self-flocculation of the magnetic particles causing vascularobstruction to vital organs in the body.

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APPLICATIONS

1] In Vaccine Delivery

2] In Case of Antigen Release

3] Targeting of Drug

4] ImmunoMicrospheres

5] MicroSponges : Topical porous Microspheres

6] Surface Modified Microspheres

7] Imaging

8] To Immobilize Enzymes

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REFERENCE

• N.K JAIN Advances in controlled & Novel drug delivery, Pg No.12,177

• S.P. VYAS and Roop. K. KHAR, controlled drug delivery, concepts & Advances. Pg No.174, 176.

• www.ijprd.comInternational Journal of Pharma. Research and development. [ISSN 0974-9446].

• http://www.stumbleupon.com/su/AmpEKq/www.authorstream.com/Presentation/ksk121087-545436-microspheres

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