1. SEMINAR BY:
B.THILAK CHANDRA
M.PHARMACY(PHARMACEUTICS),(II-Semester)
VAAGDEVI INSTITUTE OF PHARMACEUTICAL SCIENCES
BOLLIKUNTA,
HANAMKONDA.
2. CONTENTS
INTRODUCTION
CLASSIFICATION OF POLYMERS.
METHODS OF PREPARATION.
MECHANISAM OF DRUG RELEASE FROM
MICROSPHERE.
CHARACTERIZATION.
APPLICATIONS.
CONCLUSION.
REFERENCES
3. INTRODUCTION
Definition of microspheres
Microparticles or microspheres are defined as small
spheres made of any material and sized from about 50
nm to about 2 mm.
The term nanospheres is often applied to the smaller
spheres (sized 10 to 500 nm) to distinguish them from
larger microspheres
Microbeads and beads are used alternatively for
microspheres.
5. Types of Microspheres
Microcapsule: consisting of an encapsulated core
particle. Entrapped substance completely surrounded by
a distinct capsule wall.
Types of Microspheres
Microcapsule Micromatrix
Micromatrix: Consisting of homogenous dispersion of
active ingredient in particle.
6. Polymers used in the Microsphere
preparation
Synthetic Polymers
Non-biodegradable
PMMA
Acrolein
Epoxy polymers
Biodegradable
Lactides and Glycolides copolymers
Polyalkyl cyanoacrylates
Polyanhydrides
8. GENERAL METHODS OF
PREPARATION
Single Emulsion techniques
Double emulsion techniques
Polymerization techniques
- Normal polymerization.
- Interfacial polymerization
Coacervation phase separation techniques
Spray drying and spray congealing
Solvent extraction
9. SIMPLE EMULSION BASED METHOD
Aq.Solution/suspension of polymer
Stirring, Sonication
Dispersion in organic phase
(Oil/Chloroform) Chemical cross
linking
(Glutaraldehyde/For
Heat denaturation CROSS LINKING maldehyde/Butanol
Microspheres in organic phase Microspheres in organic phase
Centrifugation, Washing, Separation
MICROSPHERES
10. DOUBLE EMULSION BASED METHOD
Aq.Solution of protein/polymer
Dispersion in oil/organic phase
Homogenization
First emulsion (W/O)
Addition of aq. Solution of PVA
Multiple emulsion
Addition to large aq. Phase
Denaturation/hardening
Microspheres in solution
Separation, Washing, Drying
MICROSPHERES
14. Emulsion polymerization
Aq.solution of NaOH
Monomer/ bioactive with intiator, surfactant
material above cmc stabilizer
Dispersion with vigorous stirring
Micellar solution of
polymer in aq.medium
polymerization
Microspheres formation
Seperation, washing, drying
Microspheres
microspheres
15. Interfacial Polymerization technique
When two reactive monomers are dissolved in immiscible
solvents, the monomers diffuse to the oil- water interface
where they react to form a polymeric membrane that
envelopes dispersed phase.
Drug is incorporated either by being dissolved in the
polymerization medium or by adsorption onto the
nanoparticles after polymerization completed.
The nanoparticle suspension is then purified to remove
various stabilizers and surfactants employed for
polymerization by ultracentrifugation and resuspending the
particles in an isotonic surfactant-free medium.
16.
17. PHASE SEPARATION METHOD
Aqueous/Organic.Solution of polymer
Drug
Drug dispersed or dissolved in polymer solution
Polymer rich globules
Hardening
Microspheres in aq./organic phase
Separation, Washing, Drying
MICROSPHERES
18. Salting-out process
An aqueous phase saturated with electrolytes (e.g.,
magnesium acetate, magnesium chloride) and containing
PVA as a stabilizing and viscosity increasing agent is
added under vigorous stirring to an acetone solution of
polymer.
In this system, the miscibility of both phases is prevented
by the saturation of the aqueous phase with electrolytes,
according to a salting-out phenomenon.
The addition of the aqueous phase is continued until a
phase inversion occurs and an o/w emulsion is formed
21. DRUG LOADING
During the preparation of microspheres or after the formation
of microspheres by incubating.
Loading into preformed microspheres has an advantage of
removing all impurities from microsphere preparation before
the drug is incorporated.
High loading can be achieved by insitu loading.
If the drug is insoluble in dispersion medium employed for
microsphere stabilization.
23. MECHANISM OF DRUG RELEASE
Degradation controlled monolithic system.
Diffusion controlled monolithic system.
Diffusion controlled reservoir system.
Erodable polyagent system.
24. Characterisation METHODS
PARAMETERS
1. PARTICLE SIZE Light microscope, scanning electron microscope,
confocal laser scanning microscopy .
AND SHAPE
2. CHEMICAL electron spectroscopy for chemical analysis (esca)
ANALYSIS
3. DEGRADATION Attenuated total reflectance Fourier Transform-
OF POLYMER Infrared Spectroscopy
MATRIX
4. DENSITY Multivolume pychnometer
DETERMINAT
ION
5. ISOELECTRIC Micro-electrophoresis
POINT
28. POTENTIAL USE OF MICROSPHERES
IN THE PHARMACEUTICAL INDUSTRY
Taste and odour masking.
Conversion of oils and other liquids to solids for ease
of handling.
Protection of drugs against the environment
(moisture, light etc.).
Separation of incompatible materials (other drugs or
excipients).
Improvement of flow of powders.
Aid in dispersion of water-insoluble substances in
aqueous media, and Production of SR, CR, and
targeted medications.
29. OTHER APPLICATIONS
Microcapsules are also extensively used as diagnostics, for
example, temperature-sensitive microcapsules for
thermographic detection of tumors.
In the biotechnology industry microencapsulated microbial
cells are being used for the production of recombinant proteins
and peptides.
Encapsulation of microbial cells can also increase the cell-
loading capacity and the rate of production in bioreactors.
A feline breast tumor line, which was difficult to grow in
conventional culture, has been successfully grown in
microcapsules.
Microencapsulated activated charcoal has been used for
hemoperfusion.
30. Microspheres are made from polymeric , waxy or protective
materials that is biodegradable synthetic polymers and
modified natural products.
Solid biodegradable microspheres incorporating a drug
dispersed or dissolved throughout particle matrix have the
potential for controlled release of the drug.
These carriers received much attention not only for prolonged
release but also for the targeting anti cancer drugs to the
tumour.
These Microspheres are free-flowing and roll with practically
no friction, that means there is no abrasion, guaranteeing a
dust-free environment.
31. MARKETED PRODUCTS
Drug Commercial Company Technology Indication
name
Risperidone RISPERDAL® Janssen®/Alker Double Schizophrenia;
CONSTA® mes, Inc. emulsion (oil bipolar I
in water) disorder
Naltrexone Vivitrol® Alkermes Double Alcohol
emulsion (oil dependence
in water)
Octreotide Sandostatin® Novartis Phase Acromegaly
LAR separation
Somatropin Nutropin® Genentech/Alk Alkermes Growth
Depota ermes ProLease® deficiencies
Technology
(Cryogenic
spray-drying)
Bromocriptine Parlodel LAR Novartis Spray dry Parkinsonism
™
Minocycline Arestin® Orapharma Periodontitis
32. CONCLUSION
The concept of microsphere drug delivery systems
offers certain advantages over the conventional
drug delivery systems such as controlled and
sustained delivery. Apart from that microspheres
also allow drug targeting to various systems such
as ocular , intranasal , oral and IV route .
Novel technologies like magnetic microspheres,
immunomicrospheres offer great advantages and
uses than conventional technologies.
33. Further more in future by combining various
other strategies, microspheres will find the
central place in novel drug delivery,
particularly in diseased cellsorting
,diagnostics, gene and genetic materials,
safe,targated and effective invivo delivery
which may have implications in gene therapy.
This area of novel drug delivery has
innumerable applications and there is a need
for more research to be done in this area.
34. REFERENCES
International Journal for Targeted & Controlled Drug
Delivery Novel Carrier Systems., S.P.Vyas., R.K.Khar,
First Edition :2002.,Reprint :2007 page no:417,453.
Review: Radioactive Microspheres for Medical
Applications.
International journal of Pharmaceutics 282 (2004) 1-
18,Review polymer microspheres for controlled drug
release.
Controlled and novel drug delivery edited by N.K.Jain
reprint 2007 pg.no.236-255.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811640.
