it contais all information about micropaticulate druge delivery system. formulation and evaluation of microparticulate drug delivery system

1. MICROPARTICLES
PRESENTED BY;
MR. SHETE SHUBHAM KAILAS
F.Y.M.PHARM
UNDER GUIDENCE OF
DR. S.F. SAYYAD
HOD AND PROFESSOR
DEPARTMENT OF PHARMACEUTICS
AMRUTVAHINI COLLEGE OF PHARMACY
SANGAMNER MAHARASHTRA
1

2. CONTENTS
•general introduction
•types
•polymers used for preparation
•release mechanism
•methods of preparation
•evaluation parameters
•applications
2

3. INTRODUCTION
• Size range from 1 -1000μm.
• Protects the drug from environment.
• Stabilization of sensitive drug.
• Elimination of incompatibility.
• Delivering therapeutic substance to the target site.
• Improved bioavailability.
• Sustained and controlled manner release.
3
Kumar et.al., IJPSR ,2011, 1(1), 19-37

4. DEFINATION:
Microparticles are nothing but in which a solid or liquid drug
is either encapsulated or dispersed into the surrounding
matrix.
IDEAL CHARACTERISTICS OF MICROPARTICLES
• The ability to incorporate reasonably high concentrations
of the drug.
• Stability.
• Controlled particle size.
• Biocompatibility with a controllable biodegradability.
4
1. Shrivastav et.al .,WJPPS , june 2012, 1 (1), 422-438.
2.Bansal1 et.al., IJPSR, 2011 ,10( 1,) 69-79
3.Ramteke et.al .,IOSRPHR, July2012, 2(4 ), 44-48

5. ADVANTAGES OF MICROPARTICLES
 Particle size reduction for enhancing solubility of the poorly soluble drug.
 Provide constant and prolonged therapeutic effect.
 Provide constant drug concentration in blood there by increasing patient
compliance.
 Decrease dose and toxicity.
 Protect the drug from enzymatic and photolytic cleavage hence found to be
best for drug delivery
 Taste and odor masking.
 conversion of liquid to free flowing solids.
5
Kadam et. al., Asian J Biomed Pharm Sci, 2015: 1-17
Kumar et.al., IJPSR ,2011, 1(1), 19-37

6. DISADVANTAGES OF MICROPARTICLES
6
Higher cost required for mfg of microspheres.
The fate of polymer or impact of polymers on products.
Reproducibility is less.
Process conditions like Temperature, pH, solvent addition may influence the
stability of core
The environmental impact like hydrolysis , oxidation of the degradation of the
products
Kadam et. al., Asian J Biomed Pharm Sci, 2015: 1-17
Kumar et.al., IJPSR ,2011, 1(1), 19-37

7. 7
TYPES OF MICROPARTICLES
MICROPARTICLES
MICROENCAPSULES
MONOCORED POLYCORED MATRIX
MICROSPHERES
BIOADHESIVE
MAGNETIC
FLOATING
RADIOACTIVE
POLYMERIC
Kumar et.al., IJPSR ,2011, 1(1), 19-37

8. 8
MICROENCAPSULE:
MONOCORED POLYCORED MATRIX
Kumar et.al., IJPSR ,2011, 1(1), 19-37

9. 9
MICROSPHERE:
Kumar et.al., IJPSR ,2011, 1(1), 19-37

10. TYPES OF MICROSPHERES
 Bioadhesive Microspheres
 Magnetic Microspheres
 Floating Microspheres
 Radioactive Microspheres
 Polymeric Microspheres
10
1. Shrivastav et.al .,WJPPS , june 2012, 1 (1), 422-438.
2.Bansali et.al., IJPSR, 2011 ,10( 1,) 69-79
3.Ramteke et.al .,IOSRPHR, July2012, 2(4 ), 44-48
4. Kadam et.a al., Asian J Biomed Pharm Sci, 2015: 1-17

11. POLYMERS USED IN PREPARATION OF
MICROSPHERES:
SELECTION OF POLYMERS :
Release drug in a predetermined fashion
Release drug at a constant rate for desired period
Ideal pharmacokinetic profile for drug
11
1. Shrivastav et.al .,WJPPS , june 2012, 1 (1), 422-438.
2.Bansal1 et.al., IJPSR, 2011 ,10( 1,) 69-79
3.Ramteke et.al .,IOSRPHR, July2012, 2(4 ), 44-48
4. Kadam et.a al., Asian J Biomed Pharm Sci, 2015: 1-17

12. 12
CLASSES OF POLYMERS
CLASSES OF POLYMERS
NON
BIODEGRADABLE HYDROGELS SOLUBLE BIODEGRADABLE

13. 13
Non biodegradable polymers: polyethylene vinyl acetate (PVA),
polydimethyl siloxam (PDS), Polyether urethane (PEU), Ethyl cellulose (EC),
Cellulose acetate (CA), Polyethylene & PVC.
Soluble polymers: PEG, HPMC, Copolymer of methacrylic acid and acrylic
acid methyl ester (Eudragit L).
Hydrogels: polyhydroxy ethyl methyl acrylate, cross linked polyvinyl alcohol
(PVA), PVP, Polyacrylamide & natural substances like dextran.
 Biodegradable Polymers: Polylactic acid , Polyglycolic acid,
Polycaprolactone (PCL).
Kumar et.al., IJPSR ,2011, 1(1), 19-37

14. 14
RELEASE MECHANISM OF DRUG FROM MICROPARTICLES :
1.DIFFUSION :
2. EROSION :
Kumar et.al., IJPSR ,2011, 1(1), 19-37

15. 15
Miléna et.al., Sci.Pharma,2019,87(20), 20-45
RELEASE MECHANISM

16. 16
Miléna et.al., Sci.Pharma,2019,87(20), 20-45

17. 17
METHOS OF PREPARATION
OF MICROPARTICLES
CHEMICAL METHOD
EMULSION
POLYMERIZATION
INTERFACIAL
POLYMERIZATION
IN SITU POLYMERIZATION
PHYSICAL METHOD
SUSPENSION CROSS LINKING
SOLVENT EVAPORATION
HOT MELT
MICROENCAPSULATION
PHASE SEPARATION
SPRAY DRYING
FLUIDIZED BED COATING
CONTROLLED COATING
RAPID EXPANSION
Kumar et.al., IJPSR ,2011, 1(1), 19-37

18. 18
SELECTION OF MICROENCAPSULATION METHOD :
REQUIREMENTS:
1. High yield and drug encapsulation efficiency.
2. Stability not be effected.
3. Biological activity not be effected.
4. Not exhibit aggregation or adherence .
5. Usable at industrial scale.

19. 19
1.EMULSION POLYMERIZATION :
CHEMICAL METHOD
Aqueous core material containing
suitable emulsifier
Drop wise addition of monomer into
this solution
Polymerization done by ppt polymer into
solution
Primary nuclei and then growing that
nuclei
Simultaneously entrapment of core
material and final micro particle is
formed

20. 20
2. INTERFACIAL POLYMERIZATION
Multifunctional monomer dissolved
in liquid core material and it will be
dispersed in aqueous phase using
dispersing agent
Coreactant amine added
Rapid polymerization at interface and
generation of capsule shell containing
core material

21. 21
3. IN SITU POLYMERIZATION
Polymerization occurs in the
continuous phase and on the
continuous side of the interface
formed by dispersed core material
Low molecular weight prepolymer
will be formed
Prepolymer grows in size and gets
deposited onto dispersed core
material and solid shell is formed

22. 22
PHYSICAL METHOD
1. SUSPENSION CROSSLINKING METHOD
Dispersion of aq.solution of the
polymer which contains core material
into immiscible organic solvent in
the form of small droplets
Suspension medium contains suitable
stabilizer
Cross linking is done by either
thermally (>500 oc) or using
crosslinking agent like formaldehyde

23. 2.EMULSION SOLVENT EVAPORATION METHOD
23
core material dispersed into
polymeric solution
aqueous solution and surfactant
homogenize using mechanical
stirrer and perform evaporation
microsphere are formed

24. 24
3. HOT MELT MICROENCAPSULATION
Polymer is melted and mixed with
solid or liquid drug
Suspended into immiscible solvent
Heated to above melting point of the
polymer under continuous stirring
Emulsion is cooled below melting
point untill droplets get solidifies

25. 25
aq /organic solution of polymer
drug dispersed in the polymer solution
polymer reached globules are formed By
changing temperature ,addition of salt,
addition of nonsolvent
microspheres formed in aq/organic
phase
separation of microspheres
4.PHASE SEPARATION/ COACERVATION METHOD

26. 5.SPRAY DRYING METHOD
26
polymer dissolved in organic solvent like
acetone, DCM
drug dispersed in polymeric solution
under homogenization
atomized in hot air stream due to solvent
evaporation small droplets are formed
formation of microspheres
separated by cyclone separator

27. 27
6.FLUIDIZED BED COATING:

28. 7.CONTROLLED COATING:
Coating material dissolved in
ScCO2
Time and pressure adjusted
in the autoclave
Coating material get ppt on
suspended material i.e core
material

29. 29
8. ENCAPSULATION BY RAPID EXAPANSION OF SCF:
ENCAPSULATON BY RAPID EXPANSION OF SCF
RESS
Active ingredients and shell
material in SCF at high
pressure then released at atm
presuure through small
nozzeles shell material
deposited on active
ingredients
GAS PROCESS
Core +shell material +SCF
anti solvent at high pressure
leads to super saturation that
precipitate the solute
PGSS
Core +shell material +SCF at
high pressure causes swelling
of shell
This mixture is heated above
glass transition temp
polymer liquifies
Upon releasing pressure
shell material deposited onto
core material

30. 30
FACTORS INFLUENCING ENCAPSULATION EFFICIENCY

31. 31
EVALUATION OF MICROPARTICALS :
1. Microsphere yield
2. Drug entrapment efficiency
3. Surface morphology
4. Particle size analysis
5. In vitro release study
6. Differential scanning calorimetry
Kumar et.al., IJPSR ,2011, 1(1), 19-37

32. 32
1. Microsphere yield:
practical yield *100
percentage yield=
therotical yield
2. Entrapment efficiency:
Qty of drug encapsulated
% EE=
Qty of drug added for encapsulation

33. 33
3. Surface morphology:
SEM

34. 34
4.Particle size analysis:
(A) Manual:
a) Optical Microscopy
b) Electron Microscopy –
(i) Transmission electron microscopy
(ii) Scanning electron microscopy
c) Sieving
d) Sedimentation (Andreason Pipette Method)
(B) Automated:
a) Particle counters –
b) (i) Optical particle counting
(ii) The counter principle
(iii) Permeability
(iv) Impaction & inertial techniques
b) Light Scattering –
(i) Dynamic light scattering
(ii) Enhance laser diffraction
c) Flow cytometry
d) Field flow fractionation

35. 35
5. In vitro release study:
i) dissolution apparatus
ii) dialysis method
6.DSC
i) stability
ii)exothermic or endothermic reactions

36. 36
1. Shrivastav et.al .,WJPPS , june 2012, 1 (1), 422-438.
2.Bansal1 et.al., IJPSR, 2011 ,10( 1,) 69-79
3.Ramteke et.al .,IOSRPHR, July2012, 2(4 ), 44-48
4. Kadam et.a al., Asian J Biomed Pharm Sci, 2015: 1-17
APPLICATIONS
1. Sustained drug delivery
2. Controlled drug delivery
3. Local drug delivery
4. Pulsatile drug delivery
5. Targeted drug delivery
8.Kumar et.al., IJPSR ,2011, 1(1), 19-37

37. APPLICATIONS
1 Bioadhesive microspheres : Buccal, oral, ocular, nasal, colonic drug
delivery
 Nasal - Gentamicin, Insulin
 GI – Glipizide
 Colonic - Insulin,
 Ocular - Methyl prednisolone
2 Magnetic microspheres :
 Used in DNA analysis
 cell isolation,
 protein purification and targetting drugs to tumour sites (Doxorubicin)
3 Floating microspheres :
 Carriers for drugs like antiviral, antifungal and antibiotic agents
 non-steroidal anti inflammatory drugs, Prednisolone, Lansoprazole
37

38. 4 Radioactive microspheres :
• For diagnostic purpose – Diagnostic radioembolization:
99mTc-macroaggregated
• human serum albumin (MAA) , Thrombus imaging in deep
vein thrombosis : 99mTc-sulfur colloid
• For therapeutic purpose - Radioembolization of liver and
spleen tumours: 90Ymicrospheres
• Local radiotherapy: 212Pb-sulfur colloid
5 Polymeric microspheres:
•Vaccine delivery: Hepatitis, Influenza , Pertussis, Diptheria
toxoid,
• Oral drug delivery of easily degraded drugs: Gene therapy with
DNA plasmids; delivery of insulin, LHRH
• Controlled drug delivery after local application : Release of
proteins, hormones and peptides over extended times
38

39. BIBLIOGRAPHY
1. Nikhil Shrivastava, a review on microspheres: methods of preparation and evaluation, world
journal of pharmacy and pharmaceutical sciences · june 2012, 1( 1), 422-438.
2. Harsh Bansal1, Simar Preet kaur2, Atul Kumar Gupta2, microsphere: methods of prepration
and applications; a comparative study, International Journal of Pharmaceutical Sciences
Review and Research 2011, 10( 1), 2011; 69-79
3. Ramteke K.H1, Jadhav V.B2, Dhole S.N. Microspheres: as carrieres used for novel drug
delivery system, IOSR Journal of Pharmacy (IOSRPHR) July2012, 2( 4) ,44-48.
4. Kadam N. R. and Suvarna V, microspheres: a brief review Asian Journal of Biomedical and
Pharmaceutical Sciences, 2015. doi: 10.15272/ajbps.v5i47.713 ,1-17
5. Miléna Lengyel 1, Nikolett Kállai-Szabó 1, Vince Antal 1, András József Laki 2,3 and István
Antal 1,*Review Microparticles, Microspheres, and Microcapsules for Advanced Drug
Delivery Sci. Pharm. 2019, 87( 20); doi:10.3390/scipharm87030020.
6. Slide Share on microspheres by M. Sowjanya.
7. Microsphere preparation Youtube
39

40. 40
8. B.Pavan Kumar*, I.Sarath Chandiran, B.Bhavya, M.Sindhuri. Microparticulate
drug delivery system: A Review, Indian Journal of Pharmaceutical Science &
Research ,2011,1(1) pp. 19-37.

41. 41