1. MICROSPHERESMICROSPHERES
Presented by,
Hinglajia Hetal Ratilal
M.Pharm- Pharmaceutics, Sem-II
14024671001
SKPCPER, Ganpat University, Kherwa
Guided by,
Dr. R. P. Patel

2. INTRODUCTION
• The oral route is considered as the most promising route of drug delivery. Conventional
drug delivery system achieves as well as maintains the drug concentration within the
therapeutically effective range needed for treatment, only when taken several times a
day.
• This results in a significant fluctuation in drug levels. A well defined controlled drug
delivery system can overcome some of the problems of conventional therapy and
enhance the therapeutic efficacy of a given drug..
• There are various approaches in delivering a therapeutic susbstance to the target site
in sustained controlled release fashion using microspheres as carrier for drug
• Administration of drugs in the form of microspheres usually improves the treatment by
providing the localization of the active substances at the site of action & by prolonging
the release of drugs.

3. POTENTIAL USE OF MICROSPHERES IN THE
PHARMACEUTICAL INDUSTRY
• Taste and odor 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.

4. PREREQUISITES FOR IDEAL MICROPARTICULATE
CARRIERS
 Longer duration of action
 Control of content release
 Increase of therapeutic efficacy
 Protection of drug
 Reduction of toxicity
 Biocompatibility
 Sterilizability
 Relative stability
 Water solubility or dispersibility
 Bioresorbability
 Targetability
 Polyvalent

5. DEFINITION OF MICROSPHERES
• Microparticles or microspheres are defined as small, insoluble, free
flowing spherical particles consisting of a polymer matrix and drug.
and sized from about 50 nm to about 2 mm.
• The term Nano spheres is often applied to the smaller spheres (sized
10 to 500 nm) to distinguish them from larger microspheres
• Ideally, microspheres are completely spherical and homogeneous in
size

6. • Microspheres are made from polymeric , waxy or protective materials
that is biodegradable synthetic polymers and modified natural
products.
• Microspheres are manufactured in both solid and hollow form. Hollow
microspheres are used as additives to lower the density of a material.
• 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.

7. TYPES OF MICROSPHERES
• Microcapsule: consisting of an encapsulated core particle. Entrapped
substance completely surrounded by a distinct capsule wall.
• Micromatrix: Consisting of homogenous dispersion of active ingredient in
particle.
Microcapsule Micromatrix
Types of Microspheres

8. POLYMERS USED IN THE MICROSPHERE
PREPARATION
Synthetic Polymers
 Non-biodegradable
• PMMA - Poly(methyl methacrylate)
• Acrolein
• Epoxy polymers
 Biodegradable
• Lactides and Glycolides copolymers
• Polyalkyl cyanoacrylates
• Polyanhydrides

9. • Natural Materials
 Proteins
• Albumins
• Gelatin
• Collagen
 Carbohydrates
• Starch agarose
• Carrageenan
• Chitosan
 Chemically modified carbohydrates
• Poly(acryl)dextran
• Poly(acryl)starch

10. ADVANTAGES
• Controlled release for longer period of time (like 1-3 months).
• Frequency is reduced and hence patient compliance is
increased.
• Constant release and hence no peaks and troughs in
concentration of drug.
• Low dose and hence toxic effect is less.
• Targeting the tissue is possible.
• Other organ toxicity is less.
• No distribution through out the body (no dilution effect)

11. DISADVANTAGES
• Intended mainly for parenteral route which causes pain.
• Forms a depot in tissue or muscle for longer period and
hence may produce pain when muscle activities are
done.
• Once administered, it is difficult to take back the dose.
• Polymer may produce toxic effects.
• High cost.

12. MECHANISMS OF DRUG RELEASE
• Degradation controlled monolithic system.
• Diffusion controlled monolithic system.
• Erodible poly agent system.

13. DEGRADATION CONTROLLED MONOLITHIC
SYSTEM.
• The drug is dissolved in the matrix is in degradation controlled monolithic
microspheres system, the dissolved and is released only on degradation of the
matrix.
• The diffusion of the drug is slow compared with the degradation of the matrix.
• When degradation as by homogeneous bulk mechanism, drug release is show
initially and increase rapidly when repaid bulk degradation starts.
• Drug release from such type of device in independent of the geometry of the
device if the degradation is by homogeneous mechanism, degradation is
confined to the surface. Hence rate of release is affected by the geometry of the
device.

14. DIFFUSION CONTROLLED MONOLITHIC
SYSTEM.
• Here the active is released by diffusion prior to or concurrent with the degradation of the
polymer matrix.
• Degeneration of the polymer matrix affects the rate of release and to be taker into
account.
• Rate of release also depends on whether the polymer degrades by homogeneous or
heterogeneous mechanism.

15. ERODIBLE POLY AGENT SYSTEM.
• In this case the active agent is chemically attach to matrix & the rate of
biodegradation of matrix is slow compared to the rate of hydrolysis of drug-polymer
bond.
• Assuming that the rate of diffusion of active agent from the matrix to the surrounding
is rapid, the rate limiting step is the rate of cleavage of bond attaching drug to
polymer matrix.
• In vitro studies in rats using labeled drug polymer conjugate showed that a fairly
constant release is obtained during the time of observation which was 5 months

16. MICROSPHERE MANUFACTURE
• Most important physicochemical characteristics that may be
controlled in microsphere manufacture are:
 Particle size and distribution
 Polymer molecular weight
 Ratio of drug to polymer
 Total mass of drug and polymer

17. GENERAL METHODS OF PREPARATION
• Single Emulsion techniques
• Double emulsion techniques
• Polymerization techniques
- Normal polymerization.
- Interfacial polymerization
• Coacervation phase separation techniques
• Emulsification-solvent evaporation method
• Spray drying and spray congealing
• Brace process

18. SINGLE EMULSION BASED METHOD
Aq.Solution/suspension of polymer
Dispersion in organic phase
(Oil/Chloroform)
Microspheres in organic phase Microspheres in organic phase
MICROSPHERES
Stirring, Sonication
CROSS LINKING
Chemical cross linking
(Glutaraldehyde/Formald
ehyde/ButanolHeat denaturation
Centrifugation, Washing, Separation

19. Aq.Solution of protein/polymer
First emulsion (W/O)
MICROSPHERES
Dispersion in oil/organic phase
Homogenization
Separation, Washing, Drying
Addition of aq. Solution of PVA
Addition to large aq. Phase
Denaturation/hardening
Multiple emulsion
Microspheres in solution
DOUBLE EMULSION BASED METHOD

20. INTERFACIAL POLYMERIZATION TECHNIQUE

21. 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 re- suspending the particles in an isotonic
surfactant-free medium.

22. PHASE SEPARATION METHOD
Aqueous/Organic.Solution of polymer
Drug dispersed or dissolved in polymer solution
MICROSPHERES
Drug
Separation, Washing, Drying
Hardening
Polymer rich globules
Microspheres in aq./organic phase

23. 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

24. EMULSIFICATION-SOLVENT EVAPORATION
METHOD

25. SPRAY DRYING AND SPRAY CONGEALING
METHOD
• These methods are based on drying of the mist of polymer and drug in air.
Depending on the removal of solvent or cooling the solution are named as
“drying” and “congealing”, respectively.
• The polymer dissolved in a suitable volatile organic solvent
(dichloromethane,acetone,etc)
• The drug in the solid form is then dissolved in polymer solution under high
speed homogenization.
• This dispersion is atomized in a stream of hot air.
• This leads to formation of small droplets from which solvent evaporates
leading to the formation of microspheres.
• These are then separated from hot air by means of cyclone separator.
• Spray congealing involves the formation of microspheres by solidifying the
melted mass of drug and polymer in the form of minute particles.

26.  Ultra Spherical Microspheres..
 Microspheres with a monodisperse grain size distribution and the
smallest divergence are manufactured by BRACE.
• Perfectly spherical Microspheres
• Monodisperse grain size, narrow size distribution with diameters
between 50µm and 5000µm
• Nonabrading, therefore dust-free
• Free flowing, porous, large surface area,soft or rigid
The BRACE-Process

27. THE BRACE-PROCESS
 A liquid is gently pumped through a vibrating nozzle system
whereupon exiting the fluid stream breaks up into uniform droplets.
 The surface tension of these droplets moulds them into perfect
spheres in which gelation is induced during a short period of free fall.
 Solidification can be induced in a gaseous and/or liquid medium
through cooling, drying, or chemical reaction.
 There are no constraints on the type of liquid—molten materials,
solutions, dispersions, sols, or suspensions can be used to
manufacture perfectly spherical Microspheres.

28. 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.

29.  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.

30. REFERENCES
 S.P.Vyas., R.K.Khar, International Journal for Targeted & Controlled Drug Delivery Novel Carrier Systems.,
 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.
 N.K.Jain ,Controlled and novel drug delivery edited by reprint 2007 pg.no.236-255.
 Donald L.Wise, Handbook of pharmaceutical controlled release technology.
 James Swarbrick, James C.Boylan ,Encyclopedia of pharmaceutical technology Editors, volume-10.
 Patrick B.Deasy, Microencapsulation and related drug delivery processes edited by.
 James Swarbrick, Encyclopedia of pharmaceutical technology , 3rd
edition volume-4 .
 www.koboproducts.com
 www.brace.com
 www.wikipedia.org
 info@polysciences.com
 www.harperintl.com.
 www.pharmacy2011foru.blogspot.com

31.  Donald L.Wise, Handbook of pharmaceutical controlled release technology.
 James Swarbrick, James C.Boylan ,Encyclopedia of pharmaceutical technology
Editors, volume-10.
 Patrick B.Deasy, Microencapsulation and related drug delivery processes edited by.
 James Swarbrick, Encyclopedia of pharmaceutical technology , 3rd
edition volume-4
.
 www.koboproducts.com
 www.brace.com
 www.wikipedia.org
 info@polysciences.com
 www.harperintl.com.
 www.pharmacy2011foru.blogspot.com