2. MICROSPHERES
Microspheres are small spherical particles,
ranging in size from 1 μm to 1000 μm.
They are spherical free flowing particles
consisting of proteins or synthetic polymers
which are biodegradable in nature.
2
5. ADVANTAGES
Improve bioavailability
Provide prolonged therapeutic effect.
Provide constant drug concentration in
blood .
Decrease toxicity.
Protect the drug from enzymatic and
photolytic cleavage
Reduce the dosing frequency and thereby
improve the patient compliance
5
6. DISADVANTAGES
The cost is more.
Process conditions like change in
temperature, pH, solvent addition, and
evaporation/agitation may influence the
stability of core particles.
Degradation of product due to heat,
hydrolysis, oxidation, solar radiation or
biological agents.
6
7. TYPES OF MICROSPHERES
Bioadhesive microspheres
Floating microspheres
Radioactive microspheres
Magnetic microspheres
Polymeric microspheres
a) Biodegradable polymeric
microspheres
b) Synthetic polymeric
microspheres 7
8. Bio-adhesive microspheres:
Adhesion of drug delivery device to the
mucosal membrane such as buccal, ocular,
rectal, nasal etc can be termed as
Bioadhesive microspheres .
8
TYPES OF MICROSPHERES
9. 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.
9
TYPES OF MICROSPHERES
10. Floating microspheres:
In floating types the bulk density is less than
the gastric fluid and so remains buoyant in
stomach.
10
TYPES OF MICROSPHERES
11. Radioactive microspheres:
radioactive microspheres deliver high
radiation dose to the targeted areas without
damaging the normal surrounding tissues.
11
TYPES OF MICROSPHERES
12. Polymeric microspheres:
The different types of polymeric
microspheres can be classified as follows:
a) Biodegradable polymeric microspheres
b) Synthetic polymeric microspheres
12
TYPES OF MICROSPHERES
14. SINGLE EMULSION
TECHNIQUE
14
Polymer in aqueous solution+ drug
Disperse in organic phase (oil/
chloroform)
Microspheres
Microspheres in organic phase
stir or sonicate
Chemical cross linking
or heat denaturation
Centrifugation ,
Wash, separation
15. DOUBLE EMULSION
TECHNIQUE
15
Polymer in aq. solution + Drug
Disperse in organic phase
First emulsion ( W/O)
Multiple emulsion(W/O/W)
Microspheres in solution
Microspheres
Homogenization or sonication
Addition of aq. sol of PVA
Addition to large aq. Phase
Separation, wash, dry
17. SOLVENT
EVAPORATION
17
Coating polymer solution
Core material disperse in liquid
manufacturing vehicle phase
Evaporation of polymer solvent
Microspheres
Core material
Dissolved or dispersed
Agitation
Heating (if need)
18. PHASE SEPARATION
COACERVATION
TECHNIQUE
18
Aq/ organic solution of polymer
Drug dispersed or dissolved in the
polymer solution
Polymer rich globules
Microspheres in aq/ organic phase
microspheres
Add drug
Phase separation induced
by different means
solidify
Separate, wash and dry
21. Techniques used for
coacervation
Change in temperature
Incompatible polymer addition
Non solvent addition
Salt addition
Polymer – polymer interaction
21
22. SPRAY DRYING AND
SPRAY CONGEALING
22
Polymer dissolved in organic phase
(acetone)
Drug is dispersed in polymer solution under high
speed homogenization/
Atomized in a stream of hot air
Separated by cyclone separator and traces of solvent is
removed by vacuum drying
microspheres
Solvent evaporation
Formation of small droplets
25. i. a ) BULK
POLYMERIZATION
25
Monomer / mixture of monomer +
initiator
Microspheres
Heated to initiate polymerization
Polymer obtained is moulded /
fragmented
26. i. b ) SUSPENSION
POLYMERIZATION
26
Monomer or composition of
monomers are heated and dispersed
in water
Microspheres
Droplets
(vigorous agitation)
27. i. c) EMULSION
POLYMERIZATION
27
Monomer + aq. Solution of NaOH +
initiator ( stir)
Polymerization occurs , microspheres
are formed
Micelles solution of polymer in aq.
medium
28. ii. INTERFACIAL
POLYMERIZATION
28
Monomer A +
water Oil phase
W/O emulsion
Add monomer B
Microspheres in
aq. Medium
Microspheres
High pressure
homogenization
polymerization
30. 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. surface chemistry :
The surface chemistry of the microspheres
can be determined using the electron
spectroscopy for chemical analysis(ESCA).
30
31. 3) Drug entrapment efficiency:
Drug entrapment efficiency can be
calculated using following equation,
% Entrapment = Actual content /
Theoretical content x 100
31
32. 4) Swelling index :
Swelling index can be calculated by using
Swelling index= (mass of swollen
microspheres –mass of dry
microspheres) 100/mass of
dried microspheres
32
33. 5 )In vitro methods:
Release studies for different type of
microspheres are carried out by using
phosphate buffer pH 6.8, mostly by
rotating paddle apparatus.
6) Adhesion property:
Freshly cut piece of pig intestine is used
(5 cm long) to determine the adhesion
property of Bio-adhesive microspheres.
33
35. APPLICATIONS
Ophthalmic Drug Delivery
Oral drug delivery
Gene delivery
Nasal drug delivery
Buccal drug delivery
Gastrointestinal drug delivery
Transdermal drug delivery
Colonic drug delivery
35
37. MICROENCAPSULATION
“Microencapsulation may be defined as
the process of surrounding or
enveloping one substance within
another substance on a very small
scale, yielding capsules ranging from
less than one micron to several hundred
microns in size.”
It is mean of applying thin coating to
small particle of solid or droplet of liquid
& dispersion.
Particle size: 50-5000 micron.
2 phases:
a) Core material
b) Coating material
37
38. TECHNIQUES TO
MANUFACTURE
Physical methods
Air-suspension coating
Multiorifice centrifugal process
Pan coating
Coacervation Process
Spray–drying
Chemical process
Solvent Evaporation
Polymerization
38
39. AIR SUSPENSION
(WURSTER METHOD)
39
Within the coating chamber, particles
are suspended on an upward moving
air stream.
Spraying of coating material on the
air suspended particles.
The cyclic process is repeated
depending upon purpose of
microencapsulation.
Air stream serves to dry the product
the core material receives an
increment of coating material
41. B) Pan Coating
41
The particles are tumbled in a pan
while the coating material is applied
slowly as solution or atomized spray
to the core
To remove the coating solvent, warm
air is passed over the coated
materials
43. 43
the rotating disc flings the particulate core
material ( liquid) droplets or solid particles
towards orifices
The counter rotating disc mounted within the
cylinder , atomizes or disperses the core
material fed through the centrally located
inlet .
When the core material arrives at the orifices
& encounters the coating material membrane
The impact & centrifugal force , generated by
the rotating cylinder , hurls the core material
through the enveloping coating membrane.
MULTIORIFICE
CENTRIFUGAL PROCESS
45. APPLICATION
For sustained or prolonged drug release.
For masking taste and odor of many drugs
to improve patient compliance.
For converting liquid drugs in a free
flowing powder.
To reduce toxicity and GI irritation
Incompatibility among the drugs can be
prevented by microencapsulation.
The drugs, which are sensitive to oxygen,
moisture or light, can be stabilized by
microencapsulation
45
46. REFERENCE
Theory and practice in novel drug delivery
system by S.P. VYAS.
MICROSPHERES: A BRIEF REVIEW
Kadam N. R. and Suvarna V Department of
Quality Assurance, SVKM’s Dr. Bhanuben
Nanavati College of Pharmacy,Vile Parle,
Maharashtra.
Leon, Lachman, Herbert A. L., Joseph, L.
K; “ The Theory And Practice Of Industrial
Pharmacy”, 3rd edition, 1990, Varghese
Publishing House,412, 428.
46