Nanoparticles

Nanoparticles are sub-nanosized colloidal structures composed of synthetic or semi synthetic polymers.

The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle matrix.

1. Presented By :
Mr. Sanket Rajiv Shinde
M. Pharmacy (QAT)
Savitribai Phule Pune University
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2. 1.What is Nanoparticle ?
2.Classification of Nanoparticles
3.Advantages of Nanoparticles
4.Disadvantages of Nanoparticles
5.Preparation of Nanoparticles
6.Equipments for Nanoparticles
7.Pharmaceutical aspects of Nanoparticles
8.Evaluation of Nanoparticles
9.Applications of nanoparticles
10.Marketed Formulations
11.Conclusion
12.References
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3. •“Nanoparticles are sub-nanosized colloidal structures
composed of synthetic or semi synthetic polymers”.
•Size range : 10–1000 nm
•The drug is dissolved, entrapped, encapsulated or attached to a
nanoparticle matrix.
•Organic and inorganic in nature
•Metalic, liposomes and dendrimers etc.
•Used as carrier molecules
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4. •The first reported nanoparticles were based on
nonbiodegradable polymeric systems.
e.g. polyacrylamide,
polymethylmethacrylate,
polystyrene etc.

•The possibilities of chronic toxicity due to tissue and
immunological response towards these polymers had
restricted their use for systemic administration.
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•This problem has been solved by using biodegradable
polymers.

•The term particulate is suggestively generalized
because they could be;
Nanospheres
Nanocapsules
Nanocrystals
Nanoparticles

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Nanoparticles
Nanospheres Nanoencapsules
These are systems in
which the drug is
confined to a cavity
surrounded by a unique
polymer membrane.
These are matrix systems
in which the drug is
physically and uniformly
dispersed.

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9. Solid Lipid Nanoparticles
Polymeric Nanoparticles
Ceramic Nanoparticles
Hydrogel Nanoparticles
Copolymerized Peptide Nanoparticles
Nanocrystals and Nanosuspensions
Functionalized Nanocarriers
Nanotubes And Nanowires
Nanospheres
Nanocapsules
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10. •New type of colloidal drug carrier system for IV.
•Consists of spherical solid lipid particles in the nm range
(50-100nm), dispersed in water or in aqueous surfactant
solution.
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Small size and relatively narrow size distribution which
provide biological opportunities for site specific drug
delivery by SLN.
Controlled release of active drug over a long period can be
achieved.
Protection of incorporated drug against chemical
degradation.
No toxic metabolites are produced.
Relatively cheaper and stable.
Ease of industrial scale production by hot dispersion
technique.

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•PNPs are defined as particulate dispersions or solid
particles with size in the range of 10-1000nm.
•Composed of synthetic or semi-synthetic Polymers.
•Biodegradable polymeric nanoparticles;
Polylactic acid (PLA), polyglycolic acid (PGA),
Polylactic - glycolic acid (PLGA), and Polymethyl
methacrylate (PMMA) Phospholipids Hydrophobic
core.

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•These are the nanoparticles made up of inorganic
(ceramic) compounds silica, (Inorganic/metal) titania
and alumina.
•Exist in size less than 50 nm, which helps them in
evading deeper parts of the body.

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•Polymeric system involving the self-assembly and self
aggregation of natural polymer amphiphiles cholesteroyl
pullulan , cholesteroyl dextran and agarose cholesterol
groups provide cross linking points.
•Drug moiety is covalently bound to the carrier instead of
being physically entrapped.

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•Pure drug coated with surfactant, Aggregation of these
particles in crystalline form.
•Drug powder dispersed in aqueous surfactant solution.
•Biological materials like proteins, enzymes, peptides etc…
are being utilized as a carriers for the drug delivery.

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•Nano particle can be administered by parenteral, oral,
nasal, ocular routes.
•By attaching specific ligands on to their surfaces, nano
particles can be used for directing the drugs to specific
target cells.
•Improves stability and therapeutics index and reduce
toxic affects.
•Both active & passive drug targeting can be achieved by
manipulating the particle size and surface characteristics
of nanoparticles.

20. •Small size & large surface area can lead to particle
aggregation.
•Physical handling of nano particles is difficult in liquid
and dry forms.
•Limited drug loading.
•Toxic metabolites may form.

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Polymeric
Nanoparticles
Polymerization
Dispersion
polymerization
(DP)
Emulsion
polymerization
(EP)
EP in an organic
continuous phase
EP in aqueous
Continuous phase
Preformed
polymer
Solvent
Evaporation
method
Solvent
Displacement
method
Salting out
tech.
Super
Critical
Fluid tech.

22. a)Size of nanoparticles required
b)Inherent properties of the drug, e.g., aqueous solubility and
stability;
c)Surface characteristics such as charge and permeability;
d)Degree of biodegradability, biocompatibility and toxicity;
e)Drug release profile desired; and
f)Antigenicity of the final product.
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23. Natural hydrophilic polymers :
•Proteins :- Gelatin, albumin, lectins, legumin.
•Polysaccharides :- alginate, dextran, chitosan, agarose.

Synthetic hydrophobic polymers :
•Pre-polymerized polymers :- Poly (e-caprolactone) (PECL), Poly
(Lactic acid)(PLA), Polystyrene
•Polymerized in process polymers :- Poly (isobutyl cyanoacrylates)
(PICA), Poly (butyl cyano acrylates)
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24. Two approaches for preparation :
1.Dispersion Polymerization (DP): Used for preparation
of biodegradable polyacrylamide & polymethyl methacrylate
(PMMA).

The acrylate or methyl methacrylate monomer is dissolved in
aqueous phase.

polymerization by γ-irradiation or chemical initiation
combined with heating to tem. above 65 ˚c.

The oligomer formed subsequently aggregate & above certain
molecular weight precipitate in the form of nanoparticles
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Polymerization Method

25. 2. Emulsion Polymerization (EP):
Monomer

Dissolved in aqueous phase which contains an initiator
which is a surfactant

Vigorous agitation

Emulsion formation

Particle smaller than 100nm

Initiator which generates either radicals or ions depending
upon the type of initiator & these radicals or ions nucleate
the monomeric unit & starts polymerization process. 25

26. •EP in an organic continuous phase :- Water soluble
monomers are polymerized.
Polyalkyl cynoacrylate (PACA) nanoparticles were
prepared by EP in continuous organic phase.
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Drug dissolved in Aq. Phase
Organic solvent (hexane, chloroform) containing
surfactant
Microemulsion & monomer diffuse in
swollen micelles
Nanospheres
Emulsified
OH¯ ions initiate polymerization

27. 1. Solvent evaporation method :
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Preformed Polymer
Example : polylactic acid nanoparticle loaded with testosterone
using poloxamer 188 as stabilizer by using homogenizer.
Drug & polymer is dissolved in organic solvent.
Emulsified with an aq. phase containing surfactant to
obtain o/w emulsion.
Organic phase is then evaporated
Nanoparticles

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Drug dissolved in organic phase (ethanol/methanol)
Emulsified with Aq. Phase
Immediate polymer precipitation because of complete
miscibility of both the phase.
Nanoparticles
Displacement of organic phase
2. Solvent displacement / Nanoprecipitation :
•Useful for slightly water soluble drug.

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3. Salting out method :
•Suitable for drug & polymers that are soluble in polar
solvent such as acetone or ethanol.
Organic Phase
Organic solvent
(Acetone), Drug polymer
Aqueous Phase
Distilled water, PVA
o/w emulsion
Nanoparticle
Mechanical stirring
Distilled water

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Super Critical Fluid (SCF)
Technique
SCF Technology
Rapid Expansion of
Supercritical solution
(RESS)
For drugs soluble in SCF
Super Critical Anti-
solvent (SCA)
For drug insoluble in
SCF

31. Drug dissolved in super critical fluid
Solution sprayed into region of low pressure
Solvent power of super critical fluid decreases
Precepitation of
nanoparticles
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Drug + Methanol
Drug is dissolved
Add Super critical fluid
(miscible with methanol)
Precepitation of drug
as fine particles

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•Formation of dry nanoparticles.
•Rapid precipitation process.
•Contain very low traces of organic solvent.
•Involves use of environment friendly solvent like super
critical carbon dioxide or nitrogen.

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•Homogenizer
•Ultra Sonicator
•Mills
•Spray Milling
•Supercritical Fluid Technology
•Electrospray
•Ultracentrifugation
•Nanofiltration

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40. •Nanoparticles should be;
–free from potential toxic impurities
–easy to store and administer
–sterile if parentral use is advocated

•Process parameters are performed before releasing
them for clinical trials;
A.Purification
B.Freeze drying
C.Sterilization
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Remark :
High molecular weight substances and impurities are
difficult to remove
1.Gel filtration :

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Remark :
•High molecular weight impurities are difficult to remove
•Time consuming process
2.Dialysis :

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3.Ultra
centrifugation :
Remark :
•Aggregation of particles
•Time consuming process

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4.Cross-flow Filtration Technique :

45. •This technique involves the freezing of the nanoparticle
suspension and subsequent sublimation of its water content
under reduced pressure to get free flowing powder material.

Advantages :
•Prevention from degradation.
•Prevention from drug leakage, drug desorption .
•Easy to handle and store and helps in long term preservation.
•Readily dispersed in water without modifications in their
physicochemical properties
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46. •Nanoparticles intended for parenteral use should be
sterilized to be pyrogen free.

•Sterilization can achieved by
•Using aseptic technique throughout their preparation,
processing and formulation.
•Subsequent sterilizing treatments like autoclaving,
irradiation.
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47. 1.Particle size
2.Density
3.Molecular weight
4.Structure and
crystallinity
5.Specific surface area
6.Surface charge &
electronic mobility
7.Surface hydrophobicity
8.Invitro release
9.Nanoparticle yield
10. Drug entrapment
efficiency
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48. 1.Particle size :
•Photon correlation spectroscopy (PCS) : For smaller particle.
•Laser diffractrometry : For larger particle.
•Electron microscopy (EM) : Required coating of conductive
material such as gold & limited to dry sample.
•Transmission electron microscopy (TEM) : Easier method &
Permits differntiation among nanocapsule & nanoparticle.
•Atomic force microscope
•Laser force microscope High resolution Scanning electron
microscope
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49. 2. Density :
•Helium or air using a gas pycnometer
•Density gradiant centrifugation
3. Molecular weight :
•Gel permeation chromatography using refractive index
detector.
4. Structure & Crystallinity :
•X-ray diffraction
•Thermoanalytical method such as,
1.Differential scanning calorimetry
2.Differential thermal analysis
3.Thermogravimetry
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50. 5. Specific surface area :
•Sorptometer;
specific surface area A = σ
Density x diameter of particle
6. Surface charge & electronic mobility :
•Surface charge of particle can be determined by measuring particle
velocity in electrical field.
•Laser Doppler Anemometry tech. for determination of Nanoparticles
velocities.
•Surface charge is also measured as electrical mobility.
•Charged composition critically decides bio-distribution of
nanoparticle .
•Zeta potential can also be obtain by measuring the electronic
mobility.
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51. 7. Surface Hydrophobicity :
•Important influence on intraction of nanoparticles with
biological environment.
•Several methods have been used,
1. Hydrophobic interaction chromatography.
2. Two phase partition.
3. contact angle measurement.
8. Invitro release :
•Diffusion cell
•Recently introduce modified Ultra-filtration tech.
•Media used : phosphate buffer
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52. 10. Drug entrapment efficiency :
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9. Nanoparticle yield :
% yield = Total weight of excipient & Drug x 100
Actual weight of product
Drug entrapment % = Mass of drug in Nanoparticles x 100
Mass of drug used in formulation

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54. EMEND
(Merck & Co. Inc)
Rapamune
(Wyeth-Ayerst Laboratories)
OLAY MOISTURIZERS
(Proctor and Gamble)
ABRAXANE
(American Biosciences, Inc.)
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55. •Nanoparticles are one of the novel drug delivery systems,
which can be of potential use in controlling and targeting drug
delivery as well as in cosmetics textiles and paints.
•Judging by the current interest and previous successes,
nanoparticulate drug delivery systems seems to be a viable and
promising strategy for the biopharmaceutical industry.
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56. 1.Encyclopedia of controlled drug delivery system edited by Edith
Mathiowitz, Pg. no:551-564.
2.Vyas S.P. , Khar R.K. Targeted & Controlled Drug Delivery, Novel
Carrier Systems, CBS Publication ,2002 ,Page No.249-277,331-387.
3.www.pharmainfo.net/reviews/nanoparticles-and-its-applications-
field-pharmacy
4.Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical
Journal of Pharmaceutical Research 2006; 5(1): 561-573
5.Google.com(images)
6.Jain N. K., Controlled and novel Drug Delivery, 1st edition 2001,
CBS Publication; 292 - 301.
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