a general description on micropsheres

1. MICROSPHERES
1
Submitted By
Neelam
Somani
Submitted to
Meenakshi
Bharkatiya

2. Microspheres Are Small Spherical Particles With
Diameter, 1µm To 1000µm.
Microspheres are free flowing particles
consisting of protein or synthetic polymer
which are biodegradable in nature.
2

3. Classification
microspheres are of two types
Microcapsules are those in which entrapped substance
is distinctly surrounded by a capsule wall
Micromatrices are in which entrapped substance is
dispersed throughout the matrix.
3

4. Types of microspheres
BIOADHESIVE
FLOATING
RADIOACTIVE
MAGNETIC
POLYMERIC
4

5.  Improved bioavailability
 Provide constant and prolong therapeutic
effect
 Provide constant concentration in the
blood
 Decrease dose and toxicity
 Protect the drug from enzymatic
degradation and photolytic cleavage so it
is the best drug delivery system for protein
 Reduce the dosing frequency and5

6. The cost is more
Reproducibility is less
Process like change in temperature , pH, solvent
addition ,evaporation may influence the stability of
core particles.
Degradation of product due to heat, hydrolysis,
oxidation ,solar radiation or biological agents .
6

7. Natural polymers
Proteins Carbohydrates
 Albumins
 Gelatin
 Collagen
 Starch agarose
 Carrageenan
 Chitosan
 Chemically mordified
carbohydrates
 Poly (acryl)dextran
 Poly (acryl)starch
 DEAE cellulose
Polymers used in microspheres
7

8. Synthetic polymers
Non – biodegradable Biodegradable
 PMMA
 Acrolein
 Epoxy polymers
 Lactides and glycolids
 Copolymers
 Polyanhydrides
 Polyalkyl
cynoacrylates
8

9. General methods of preparation
 Simple emulsion technique
 Double emulsion technique
 Polymerization techniques
 Normal polymerization
 Interfacial polymerization
 Coacervation phase separation techniques
 Spray drying and congealling
 Solvent extraction
9

10. Single emulsion technique
 The natural polymers are dissolved or dispersed in
aqueous medium followed by dispersion in the non –
aqueous medium e.g.oil.
 In the second step of preparation, cross linking of the
dispersed globules is carried out .
 The cross-linking can achieved either by means of heat or
by using the chemical cross linkers.
 The chemical cross-linking agents used include
glutaraldehyde, formaladehyde, terephthaloyl chloride ,
diacid chloride ,etc.
10

11. 11

12. Double emulsion technique
 This method involves the formation of the multiple
emulsions and best suited to the water-soluble drugs,
peptides, proteins and the vaccines.
 This method can be used for both the natural as well as
the synthetic polymer .
 The aqueous protein solution is dispersed in a lipophilic
organic continuous phase. This protein solution may
contain the active constituents.
 The continuous phase is generally consisted of the
polymer solution that eventually encapsulates the protein
contained in dispersed phase.
12

13. Double emulsion technique
 The primary emulsion is then subjected to homogenization
or sonication before adding to aqueous polyvinyl alcohol
solution.
 This results in the formation of double emulsion .the
emulsion is subjected to solvent removal by solvent
evaporation or extraction process.
 The solvent evaporation is carried out by maintaining
emulsion at reduced pressure or by stirring the emulsion so
that the organic phase evaporate.
 Then the emulsion is added to larger quantity of water into
which organic phase diffuses out.13

14. 14

15. Double emulsion technique
 The solid microspheres are obtained by
subsequent filtration and washing.
 A number of hydrophilic drugs like leutinizing
hormone releasing hormone (LH-RH)
agonist,vaccines , protein /peptides are
incorporated into microspheres using this method.
15

16. Phase separation coacervation
technique
 Phase separation method is specially designed for preparing the
reservoir type of the system to encapsulate water soluble drugs
e.g. peptides , proteins.
 Some of the preparations are of matrix type particularly, when
the drug is hydrophobic in nature e.g. steroids.
 In matrix type device, the drug or the protein is soluble in the
polymer phase.
 The process is based on the principle of decreasing the solubility
of the polymer in the organic phase to affect the formation of the
polymer rich phase called the ‘coacervates’.
16

17. Phase separation coacervation
technique
 In this technique the polymer is first dissolved in a suitable
solvent and then drug is dispersed by making its aqueous
solution , if hydrophillic or dissolved in the polymer solution itself,
if hydrophobic .
 Phase separation is then accomplished by changing the solution
conditions by using any of the method mentioned.
 The process is carried out under continuous stirring to control the
size of the microparticles.
Salt addition
Non-solvent addition
Addition of incompatible polymer
Change in pH
17

18. 18

19. Spray drying and spray
congealing
 Spray drying and spray congealing methods are based on drying of
the mist of the polymer and drug in the air.
 The polymer is first dissolved in as suitable volatile organic solvent
such as dichloromethane ,acetone ,etc.
 The drug in the solid form is then dispersed in the polymer solution
under high –speed homogenization.
 The atomization leads to the formation of the small droplets or the
fine mist from which the solvent evaporates instantaneously leading
the formation of the microspheres in a size range 1-100 um.
 Micro particles are separated from the hot air by means of the
cyclone separator while the traces of solvent are removed by
vacuum drying.
19

20. 20

21. Spray drying and spray
congealing
 One of the major advantages of the process is feasibility of
operation under aseptic conditions.
 The two processes are rapid, requiring single stage operation ,
suitable for both batch and bulk manufacturing.
 These techniques have been used to encapsulate a large
number of the drugs. The spray drying process is used to
encapsulate various penicillins.
21

22. SOLVENT EXTRACTION
 It involves the removal of the organic phase by the extraction of
the organic solvent.
 Organic phase removed by extraction with water, this process
decreases the hardening time for the microspheres.
 The drug or protein is added directly to the polymer organic
solution .
 Removal of solvent depend on :-
 1. Temperature of water
 2. Ratio of emulsion volume to the water
 3. Solubility profile of the polymer
22

23. 23

24. Conclusion
Microspheres are having wide applications in
drug delivery system ,controlled and sustained
drug delivery. By combining various strategies
,microsphere will find central place in novel
drug delivery mainly particularly in cell sorting
,diagnostics and genetic engineering.
24

25. References
25

26. Thank
you
26