Microspheres are solid spherical particles ranging from 1-1000μm that are used for drug delivery. They can be made of proteins or synthetic polymers. There are two main types - microcapsules which have a core and coating, and micromatrices which have a drug dispersed throughout the polymer matrix. Microspheres offer advantages like reduced dosing, constant drug levels, and protection of drugs. They are made using methods like solvent evaporation, emulsion techniques, and polymerization. Microspheres find applications in delivery to sites like the eyes, oral cavity, skin and more. Evaluation involves analyzing size, shape, drug content and release kinetics.

1. MICROSPHERES
PRESENTED BY:
Dhruv J. Patel
M. Pharm.2nd semester(2017-2018)
GUIDED BY:
Dr. Sunita A. Chaudhary
Arihant school of pharmacy & BRI, Adalaj
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2. INTRODUCTION
• Microspheres are solid spherical particles ranging
in size from 1-1000µm. They are spherical free
flowing particles consisting of proteins or
synthetic polymers.
• The microspheres are free flowing powders
consisting of proteins or synthetic polymers,
which are biodegradable in nature.
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3. • There are two types of microparticles
• 1) Microcapsules
• 2)Micromatrices.
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4. ADVANTAGES OF MICROSPHERES
1. Particle size reduction for enhancing solubility of the poorly
soluble drug.
2. provide constant and prolonged therapeutic effect.
3. provide constant drug concentration in blood there by
increasing patent compliance.
4. Decrease dose and toxicity.
5. Protect the drug from enzymatic and photolytic cleavage
hence found to be best for drug delivery.
6. Reduce the dosing frequency and thereby improve the patient
compliance
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5. 7. Better drug utilization will improve the bioavailability
and reduce the incidence or intensity of adverse
effects.
8. Protects the GIT from irritant effects of the drug.
9. Biodegradable microspheres have the advantage over
large polymer implants in that they do not require
surgical procedures for implantation and removal.
10. Controlled release delivery biodegradable microspheres
are used to control drug release rates there by
decreasing toxic side effects, and eliminating the
inconvenience of repeated injections.
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6. DISADVANTAGES
1. The costs of the materials and processing of the controlled
release preparation, are substantially higher than those of
standard formulations.
2. The fate of polymer matrix and its effect on the
environment.
3. The fate of polymer additives such as plasticizers ,
stabilizers, antioxidants and fillers.
4. Reproducibility is less.
5. Process conditions like change in temperature, pH,
solvent addition, and evaporation/agitation may influence
the stability of core particles to be encapsulated.
6. The environmental impact of the degradation products of
the polymer matrix produced in response to heat,
hydrolysis, oxidation, solar radiation or biological agents.
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7. Ideal characteristics of microspheres
• The ability to incorporate reasonbly high concentration of
the drug.
• Stability of the preparation after synthesis with a
clinically acceptable shelf life.
• Controlled particle size and dispersability in aqueous
vehicles for
injection.
• Release of active reagent with a good control over a wide
time scale.
• Biocompatibility with a controllable biodegradability.
• Susceptibility to chemical modification.
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8. TYPES OF MICROSPHERES:
1. Bioadhesive
microspheres
2. Magnetic
microspheres
3. Floating
microspheres
4. Radioactive
microspheres
5. Polymeric
microspheres
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9. 1. Bioadhesive microspheres:
• Adhesion can be defined as sticking of drug to
the membrane by using the sticking property of
the water soluble polymers.
• Adhesion of drug delivery device to the mucosal
membrane such as buccal, ocular, rectal, nasal
etc. can be termed as bio adhesion.
• These kinds of microspheres exhibit a prolonged
residence time at the site of application and
causes intimate contact with the absorption site
and produces better therapeutic action.
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10. 2. Magnetic microspheres:
• This kind of delivery system is very much
important which localises the drug to the disease
site.
• Magnetic carriers receive magnetic responses to a
magnetic field from incorporated materials that
are used for magnetic microspheres are chitosan,
dextran etc.
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11. a.Therapeutic magnetic microspheres used to
deliver chemotherapeutic agent to liver tumour.
Drugs like proteins and peptides can also be
targeted through this system.
b.Diagnostic microspheres, used for imaging liver
metastases and also can be used to distinguish
bowel loops from other abdominal structures by
forming nano size particles supramagnetic iron
oxides.
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12. 3. Floating microspheres:
• In floating types the bulk density is less than the
gastric fluid and so remains buoyant in stomach
without affecting gastric emptying rate.
• The drug is released slowly at the desired rate,
and the system is found to be floating on gastric
content and increases gastric residence and
increases fluctuation in plasma concentration.
• Moreover it also reduces chances of dose
dumping.
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13. 4. Radioactive microspheres:
• Radio embolization therapy microspheres sized
10-30 nm are of larger than the diameter of the
capillaries and gets tapped in first capillary bed
when they come across.
• They are injected in the arteries that leads them
to tumour of interest so all these conditions
radioactive microspheres deliver high radiation
dose to the targeted areas without damaging the
normal surrounding tissues.
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14. 5. Polymeric microspheres:
• The different types of polymeric
microspheres can be classified as
follows and they are biodegradable
polymeric microspheres and
Synthetic polymeric microspheres.
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15. • i) Biodegradable polymeric microspheres:
Natural polymers such as starch are used with the
concept that they are biodegradable,
biocompatible, and also bio adhesive in nature.
Biodegradable polymers prolongs the residence
time when contact with mucous membrane due to
its high degree of swelling property with aqueous
medium , results gel formation.
The rate and extent of drug release is controlled by
concentration of polymer and the release pattern
in a sustained manner.
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16. ii) Synthetic polymeric microspheres:
• Synthetic polymeric microspheres are widely used
in clinical application, moreover that also used as
bulking agent, fillers, embolic particles, drug
delivery vehicles etc.
• main disadvantage of these kind of microspheres,
are tend to migrate away from injection site and
lead to potential risk, embolism and further organ
damage.
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17. METHOD OF PREPARATION:
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8. Quassi
emulsion
solvent
diffusion6.
POLYMERISATION
TECHNIQUE
7. Solvent
extraction
5. Phase
separation
coacervation
technique
1. Spray
Drying
2. Solvent
Evaporation
3. Single
emulsion
technique
4. Double
emulsion
technique
17

18. 1. Spray Drying
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• Polymer dissolve in volatile organic solvent (acetone, dichloromethane)
Drug dispersed in polymer solution under high speed
homogenization
Atomized in a stream of hot air
Due to solvent evaporation small droplet or fine mist form
Leads to formation of Microspheres
Microspheres separated from hot air by cyclone separator, Trace of solvent
are removed by vacuum drying
18

19. 2. Solvent extraction
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• Drug is dispersed in organic solvent
(water miscible organic solvent such as Isopropanol)
Polymer in organic solvent
Organic phase is removed by extraction with water .
(This process decreasing hardening time for microspheres)
Hardened microspheres
19

20. 3. Single emulsion technique
• The micro particulate carriers of natural polymers.
• The natural polymers are dissolved or dispersed in
aqueous medium followed by dispersion in non-aqueous
medium like oil.
• In the next step, the cross linking of the dispersed globule
is carried out. The cross linking can be achieved either by
means of heat or by using the chemical cross linkers and
then subjected to centrifugation, washing, separation.
• The nature of the surfactants used to stabilize the
emulsion phases can greatly influence the size, size
distribution, surface morphology, loading, drug release,
and bio performance of the final multiparticulate product.
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21. 4. Double emulsion technique
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Aq.Solution of protein/polymer
Dispersion in oil/organic phase Homogenization
First emulsion(W/O)
Addition of aq. Solution ofPVA
Multiple emulsion
Addition to large aq.Phase
Denaturation/hardening
Microspheresinsolution
Separation, Washing, Drying
MICROSPHERES
21

22. 5. Phase separation coacervation
technique
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Aqueous/Organic Solution of polymer
Drug
Drug dispersed or dissolved in polymer solution
Phase seperation induced by various means
Polymer rich globules
Hardening
Microspheres in aq./organic phase
Separation, Washing, Drying
MICROSPHERES 22

23. Steps of Coacervation
Formation of
three
immiscible
chemical
phases
Deposition of
the coating
Rigidization of
the coating
6

24. Overview of Coacervation 7

25. Techniques Used for
Coacervation
Change In
Temperature
Incompatible
Polymer
Addition
Non-solvent
Addition
Salt Addition
Polymer-
Polymer
Interaction
8

26. Temperature
Change
Under proper
polymer
concentration,
temperature and
agitation, liquid
polymer coalesce
around dispersed
core and form
embryonic micro
particles.
9

27. Incompatible Polymer
Addition
Usage of
dissimilar
polymer in
common solvent
can be done for
preparation of
micro particles.
10

28. Non-Solvent
Addition
Liquid, which is
non- solvent for
polymer, is used
for coacervation.
11

29. Salt
Addition
Soluble inorganic
salts are added to
aqueous solutions
of water soluble
polymers for phase
separation
12

30. Polymer
Interaction
Interaction of
oppositely charged
polyelectrolytes result
in the formation of
complex with
reduced solubility
that phase
separation occurs.
13

31. 6.POLYMERISATION
TECHNIQUE
• NORMAL POLYMERIZATION:-
BULK POLYMERIZATION:-
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MONOMR OR
COMBINATION
OF
MONOMERS
INITIATOR OR
CATALYST
HEATED POLYMER
MOULDED
MICROSPHERES
Drug loading may be done during the
polymerization process
31

32. SUSPENSION
POLYMERIZATION
Monomer
Vigorous ,Aggitation
Bioactive material Initiator
Dispersion in water & stabilizer
Droplet
Polymerization by Heat
Hardened microspheres
Separation & Drying
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33. EVALUATION OF MICROSPHERES
1. Particle size and shape :- The most widely used
procedures to visualize microparticles are conventional
light microscopy (LM) and scanning electron
microscopy (SEM).
2. Electron spectroscopy for chemical analysis: The
surface chemistry of the microspheres can be
determined using the electron spectroscopy for
chemical analysis (ESCA).
3. Density determination: The density of the microspheres
can be measured by using a multi volume pycnometer.
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34. 4. Isoelectric point: The micro electrophoresis is used to
measure the electrophoretic mobility of microspheres
from which the isoelectric point can be determined.
5. Angle of contact: The angle of contact is measured to
determine the wetting property of a micro particulate
carrier.
6. In vitro methods: Release studies for different type of
microspheres are carried out by using different suitable
dissolution media, mostly by rotating paddle apparatus
(USP / BP).
7. Drug entrapment efficiency: Drug entrapment efficiency
can be calculated using following equation, %
Entrapment = Actual content/Theoretical content x 100.
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35. 8. Swelling index : The swelling index of the
microsphere was calculated by using the
formula, Swelling index= (mass of swollen
microspheres - mass of dry microspheres/mass
of dried microspheres) 100.
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36. APPLICATION OF MICROSPHERES IN
PHARMACEUTICAL INDUSTRY
1. Ophthalmic Drug Delivery
• Polymer exhibits favorable biological behavior such as
bioadhesion, permeability-enhancing properties, and
interesting physico-chemical characteristics, which make it a
unique material for the design of ocular drug delivery vehicles.
Due to their elastic properties, polymer hydro gels offer better
acceptability, with respect to solid or semisolid formulation,
for ophthalmic delivery, such as suspensions or ointments.
2. Oral drug delivery
• The potential of polymer films containing diazepam as an oral
drug delivery was investigated in rabbits. The ability of
polymer to form films may permit its use in the formulation of
film dosage forms, as an alternative to pharmaceutical tablets.
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37. 3. Gene delivery
• Gene delivery systems include viral vectors, cationic liposomes,
polycation complexes, and microencapsulated systems. Viral
vectors are advantageous for gene delivery because they are
highly efficient and have a wide range of cell targets.
4. Nasal drug delivery
• The nasal mucosa presents an ideal site for bioadhesive drug
delivery systems. Polymer based drug delivery systems, such as
microspheres, liposomes and gels have been demonstrated to
have good bioadhesive characteristics and swell easily when in
contact with the nasal mucosa increasing the bioavailability and
residence time of the drugs to the nasal route.
5. Intratumoral and local drug delivery
• Intratumoral and local drug delivery strategies have gained
momentum recently as apromising modality in cancer therapy.
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38. 6. Buccal drug delivery
• Buccal tablets based on chitosan microspheres containing chlorhexidine
diacetate gives prolonged release of the drug in the buccal cavity
improving the antimicrobial activity of the drug.
• Polymer microparticles with no drug incorporated have antimicrobial
activity due to the polymer.
7. Gastrointestinal drug delivery
• Floating hollow microcapsules of melatonin showed gastroretentive
controlled-release delivery system. Release of the drug from these
microcapsules is greatly retarded with release lasting for 1.75 to 6.7hours
in simulated gastric fluid.
8. Transdermal drug delivery
• Polymer has good film-forming properties. The drug release from the
devices is affected by the membrane thickness and cross-linking of the
film. Chitosan-alginate polyelectrolyte complex has been prepared in-situ
in beadsand microspheres for potential applications inpackaging,
controlled release systems and wound dressings.
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39. 9. Colonic drug delivery
• Polymer has been used for the specific delivery of insulin to the
colon. The chitosan capsules were coated with enteric coating
(Hydroxy propyl methyl cellulose phthalate)and contained,
apart from insulin, various additional absorption enhancer and
enzyme inhibitor.
10. Vaginal drug delivery
• Polymer, modified by the introduction of thioglycolic acid to the
primary amino groups of the polymer, embeds clotrimazole,
animidazole derivative, is widely used for the treatment of
mycotic infections of the genitourinary tract.
11. Targeting by using microparticulate carriers
• Microcrystalline cellulose was used as additive in
concentrations range from 0-70 %.The powder mixture was
extruded using water and dilute acetic acid in different powder
to liquid ratios.
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40. Recent Advancements in Microspheres
• Important utilizations of chitosan polymer
Cholesterol-lowering effects
• Orthopaedic Patients
• Cosmetics industry
• Increase Stability of Drug
• Dental Medicine
• Enhanced Bone Formation by transforming
growth factor(TGF-pl)
• Wound Healing Properties
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41. DHRUV J.PATEL 41

42. REFERENCES
1. Jamini M., and Rawat S., A review on microsphere,
Res. j. pharm. boil. chem. sci. 2013; 4,(1):1223-33.
2. Patel N. R., Patel D. A., Bharadia P.D., Pandya V.,
Modi D.,Microsphere as a novel drug delivery, Int. j.
pharm. life sci. 2011;2(8):992-7.
3. Singh C., Purohit S., Singh M., Pandey B.L., Design
and evaluation of microspheres: A Review, jddr.
2013;2(2):18-27.
4. Prasanth v.v., Moy A. C., Mathew S. T., Mathapan R.,
MicrospheresAn overview, Int. J. Res. Pharm. Biome
d. Sci., 2011;2:3328
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43. REFERENCES
5. Kadam N. R. and Suvarna V., MICROSPHERES: A
BRIEF REVIEW, Department of Quality Assurance,
SVKM’s Dr. Bhanuben Nanavati College of
Pharmacy, Vile Parle, Mumbai-400 056.
Maharashtra, India
6. Ramteke K.H., Jadhav V.B., Dhole S.N.,
Microspheres: As carrieres used for novel drug
delivery system, IOSRPHR. 2012;2(4):44-48.
7. Leon Lachman, Herbert A. Lieberman, Joseph L.
Kanig,“The Theory and Practice of Industrial
Pharmacy”, 3rd edition, pp.420.
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44. DHRUV J.PATEL 44
“One should avoid carrying out an experiment
requiring more than 10 per cent accuracy.”
― Walther Nernst