1. MICROSPHERES &
MAGNETIC MICROSPHERES
PRESENTED BY GUIDED BY
K. Swapna Dr.Yasmin begam
256213886015 M.Pharm, Ph.D

2. CONTENTS
 INTRODUCTION
 CONCEPT
 ADV AND DISADV
 MATERIALS REQUIRED
 IDEAL MICROSPHERE PREREQUISITES
 METHOD OF PREPARATION
 CHARACTERIZATION or EVALUATION
 APPLICATIONS
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3. 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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4. 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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5. 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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6. 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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7. 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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8. METHOD OF PREPARATION
Single Emulsion Technique
Double Emulsion Technique
Polymerization techniques
Normal polymerization
Interfacial polymerization
Coacervation technique
Spray Drying & Spray Congealing
Solvent Extraction
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9. 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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10. Aq solution/suspension of polymer
Dispersion in org phase oil/chloroform
Cross linking
Heat/Denaturation Chemical
Microspheres in org phase Microspheres in org phase
Centrifugation, washing, separation
Micro spheres
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11. 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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12. Aq sol of protein/polymer drug (if present)
Dispersed in Oil
Homogenization
First emulsion
Addition of aq sol of PVA
Multiple emulsion
Addition to large aq phase(Denaturation)
Micro spheres in solution
Separation, washing, drying
Micro spheres
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13. POLYMERIZATION TECHNIQUES
Normal polymerization
Bulk polymerization,
Suspension precipitation and
Emulsion polymerization
Interfacial polymerization
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14. BULK POLYMERIZATION
Monomer, Bioactive material, Initiator
Polymerization
Polymer Block
Mould/ mechanical fragmentation
Microspheres
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15. SUSPENSION POLYMERIZATION
Monomer, Bioactive material, Initiator
Dispersed in water & stabilizer
Droplets
Vigorous agitation, heat
Separation & drying
MICROSPHERES >100μM
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16. EMULSION POLYMERIZATION
Monomer/ bioactive material Aq sol of NaOH, initiator, surfactant
Vigorous stirring
Micellar sol of polymer in aq medium
polymerisation
Microspheres formation
Separation, washing, drying
MICROSPHERES
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17. 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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18. COACERVATION TECHNIQUE
Aq/ org sol of polymer
Drug dispersed in polymer sol
Phase separation
Polymer rich globules
Microspheres in aq/ org phase
Microspheres
Hardening
Separation, drying
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19. 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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20. 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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21. 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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22. 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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23. 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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24.  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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25. 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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27. CONTENTS
 1] INTRODUCTION
 2] CONCEPT
 3] IDEAL CHARACTERISTICS
 4] MATERIALS CREATING MF
 5] ADVANTAGES AND DISADVANTAGES
 6] APPLICATIONS
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28. INTRODUCTION
 DEFINITION :
 Magnetic Microspheres (MM):
 These are microspheres, containing magnetic
substance inside which, can be easily targeted by
applying external magnetic field.
 They were mainly developed to minimize renal
clearance and to increase target site specificity. This
system has a great potential in the treatment of
localized tumors in the regions of well-defined blood
supply.
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29. 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 still
continued to lodge at the target site, presumable because they had lodged
in the vascular endothelium, penetrated in to the interstitial space,
resulting in their retention.
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30. 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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31. 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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32. 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 FeOfe203
having a molecular weight of 231.55 with a chemical
composition of Fe=72.36%, O=27.64%.
The Ferro magnetic material when incorporated into
microspheres makes them magnetically responsive, so that
they can be concentrated to the desired site by applying some
external magnetic field.
OTHER MF CREATORS ARE : ADRIAMYCIN,
VINDESIN SULPHATE
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33. ADVANTAGES :
Incorporation of magnetically responsive materials into microspheres
makes them susceptible to applied magnetic field, so that they are
concentrated to the target site by application of magnetic field externally
to that site. Due to this, rapid clearance of these microspheres by RES is
prevented.
Microspheres can transit into extra vascular space creating an extra
vascular depot of drug for sustained release of drug within the targeted
areas.
Increase of tumor targeting microspheres can be internalized by tumor
cell due to its much-increased phagocytic activity as compared to
normal cell. So the problem of drug resistance due to inability of drug
to be transported across the cell membrane can be prevented.
Controlled and predictable rate of drug release with smaller doses of
drug can be achieved.
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34. DISADVANTAGES
One of the major limitations of this system is, the drug cannot
be targeted to deep-seated organism in the body. This approach
is confined to the targeting of drugs to the superficial tissues
like 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 liver
and the regions of RES and the dangerous effect of self-flocculation
of the magnetic particles causing vascular
obstruction to vital organs in the body.
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35. 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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36. 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.com
International Journal of Pharma. Research and
development. [ISSN 0974-9446].
• http://www.stumbleupon.com/su/AmpEKq/www.authorstre
am.com/Presentation/ksk121087-545436-microspheres
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