microsphere,METHOD OF PREPARATION,SINGLE EMULSION TECHNIQUE,DOUBLE EMULSION TECHNIQUE,SOLVENT EVAPORATION, PHASE SEPARATION COACERVATION TECHNIQUE,SPRAY DRYING AND SPRAY CONGEALING,SOLVENT EXTRACTION,POLYMERIZATION,EVALUATION OF MICROSPHERES,MICROCAPSULES,MICROENCAPSULATION,AIR SUSPENSION ,Pan Coating,MULTIORIFICE CENTRIFUGAL PROCESS

1. Presented by
P.Pavazhaviji
M.Pharm I Year (II Sem)
Dept. of Pharmaceutics
MTPG & RIHS
Puducherry 1

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

3. CLASSIFICATION
Microspheres
Microcapsules Micromatrices
 Microcapsules consisting of an encapsulated
core particle .
 Micromatrices in which entrapped substance is
dispersed throughout the matrix.
3

4. 4

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

13. METHOD OF PREPARATION
 Single emulsion technique
 Double emulsion technique
 Solvent evaporation
 Phase separation coacervation technique
 Spray drying and spray congealing
 Solvent extraction
 Polymerization 13

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

16. 16

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

19. Steps of coacervation
Formation
of three
immiscible
chemical
phases
Deposition
of the
coating
Rigidization
of the
coating
19

20. 20

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

23. 23
 SOLVENT EXTRACTION

24.  POLYMERIZATION
24
polymerization
normal
interfacial
Emulsion
polymerization
Suspension
polymerization
Bulk
polymerization

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

29. 29

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

34. 34

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

36. MICROCAPSULES
Microcapsules :
Microcapsules consisting of an
encapsulated core particle .
Entrapped substance completely
surrounded by a capsule distance
wall.
36

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

40. 40

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

42. 42

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

44. 44

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.
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