Nanoparticles

 Introduction of Nanoparticles
 Solid lipid Nanoparticles
 Advantage & disadvantages of SLNs
 Methods of Preparation
 Sterilization Criteria
 Characterization of SLNs
 Applications of SLNs
 References

NANOTECHNOLOGY-

It comprises technological developments on the
nanometer scale, usually 0.1 to 100 nm.
Nanotechnology, the science of the small.

Nano is Greek for dwarf, and nanoscience deals with
the study of molecular and atomic particles.

 NANOSUSPENSIONS : They are colloidal
dispersions of nanosized drug particle that are
produced by suitable method and stabilized by
suitable stabilizer .

 NANOPARTICLES : They are solid colloidal
particles sized from 30-100 nm .

 NANOSPHERES : Polymer matrices in which drug
is dissolved or dispersed .

 NANOCAPSULES : Consists of polymer wall
entrapping an oily core in which the drug is
dissolved

 NANOPARTICLES :
Nanoparticles are particles made of natural or
synthetic polymers ranging in size from 50 to 500 nm.
They consist of macromolecular materials in which
the active principle ( drug or biologically active
material ) is dissolved, entrapped, and or to which the
active principle is adsorbed or attached.

MATRIX RESERVIOR
type type

Nanospheres- are solid core spherical particulates,
which contain drug embedded within the matrix or
adsorbed onto the surface.(Matrix type)
Nanocapsules- are vesicular system in which drug is
essentially encapsulated within the central core
surronded by a polymeric sheath.(Reservoir type

POLYMERIC
NANOPARTICLES
LIPOSOMES QUANTUM
DOTS

NANOPARTICULATE
DENDRIMERS NIOSOMES
CARRIERS

SOLID LIPID NANOSHELLS
NANOPARTICLES CARBON
NANOTUBES

 The solid lipid nanoparticles(SLN’s) are submicron colloidal carriers which are

composed of physiological lipid, dispersed in water or in an aqueous
surfactant solution.
 They consist of macromolecular materials in which the active principle ( drug

or biologically active material ) is dissolved, entrapped, and or to which the
active principle is adsorbed or attached.
 Nanoparticles are particles made of natural or synthetic polymers ranging in

size from 50 to 500 nm.
 No potential toxicity problems as organic solvents are not used.

Phospholipids monolayer

 Small size & narrow size distribution provides for site specific drug
delivery by SLNs

 Controlled release of active drug over a long period can be achieved

 Protection of incorporated drug against chemical degradation

 No toxic metabolites are produced

 Sterilization can be done by autoclaving or gamma irradiation

 Surface modification can be easily done

 Drug Loading capacity is limited

 High pressure induce drug degradation

 Coexistences of several colloidal species

 Lipid crystallization & drug incorporation

- supercooled melts
- gelation phenomenon
 Drug expulsion

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 High pressure homogenization:
Hot homogenization
Cold homogenization
 Ultrasonication /high speed homogenization:
 Solvent emulsification/evaporation
 Micro emulsion based SLN preparations
 SLN preparation by using supercritical fluid
 Spray drying method

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Melting of the lipid & dissolving/dispersing of the drug in the lipid

Dispersing of the drug loaded lipid in a hot aqueous surfactant mixture.

Premix using a stirrer to form a coarse preemulsion

High pressure homogenization at a temperature above the lipid M.P.

Hot O/W nanoemulsion

Solid Lipid Nanoparticles

Disadvantages: 1) temperature induce drug degradation
2) partioning effect
3) complexity of the crystallization
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Melting of lipid & dissolving/dispersing of the drug in the lipid

Solidification of the drug loaded lipid in liquid nitrogen or dry ice

Grinding in a powder mill

Dispersing the powder in a aqueous surfactant dispersion medium

High pressure homogenization at room temperature or below.

Solid Lipid Nanoparticles

Disadvantages: 1) Larger particle sizes & broader size distribution
2) does not avoid thermal exposure but minimizes it
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SLN were also developed by high speed stirring or
sonication
 Adv. :
1) Equipment used is very common
2) No temperature induced drug degradation
 Disadv.:
1) Potential metal contamination
2) Broader particle size distribution ranging
into micrometer range.

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 Lipophilic material is dissolved in a water immiscible organic
solvent (e.g.cyclohexane) that is emulsified in an aqueous phase.

 Upon evaporation of solvent, a nanoparticle dispersion is
formed by precipitation of lipid in aq. Medium.

The mean diameter of the obtained particles was 25 nm with
cholesterol acetate as model drug and lecithin/sodium
glycocholate blend as emulsifier.

Adv:- Avoidance of any thermal stress.
Disadv:- use of organic solvents.
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 Preparation by stirring optically transparent mixture at 65-70 o c
composed of a low melting fatty acid, emulsifier, coemulsifier &
water.
 This hot microemulsion dispersed in cold water (2-3oc) &
stirring.

By using Supercritical fluid
 Can be prepared by Rapid Expansion of Supercritical Carbon
dioxide solution methods(RESS)
 Carbon dioxide with 99.99% is good solvent.

 Adv:- 1) Solvent less processing.

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Alternative procedure to lyophilization in in order to transform
an aqueous SLN dispersion into a drug product.

 Disadvantages:-
1) particle aggregation due to high temp., shear forces & partial

melting of particles.
2) Recommended use of lipid with M.P. >700 c for spray
drying.

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For parentral & ocular administration SLNs must be
sterile.
For lecithin stabilized SLNs autoclaving is possible & it is
not possible for sterically stabilized polymers.
Physical stability during autoclave can not be stated, it
depends on composition.
SLN dispersion can also be sterilized by filtration.

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[I] Measurement of particle size
 Photon correlation spectroscopy
 Transmission electron microscopy
 Scanning electron microscopy

[II] Measurement of Zeta Potential
 Allows predictions about the storage stability of colloidal
dispersion

 Zeta potential under 30 mV are required for full electrostatic
stabilization.

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 Gel chromatography
 Atomic force microscopy

[IV] Surface element analysis
 X-ray photoelectron spectroscopy
 Electrophoresis
 Laser Doppler anaemometry

[V] Density
 Helium compression pychnometry
 Contact angle measurement

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[VI] Molecular analysis
 H-NMR
 Infra red analysis

[VI] Measurement of Crystallinity, Lipid modification
 DSC and
 X-ray scattering used to investigate status of lipid

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 Solid lipid Nanoparticles possesses a better stability and ease
of up grad ability to production scale as compared to
liposomes.

 SLNs form the basis of colloidal drug delivery systems, which
are biodegradable and capable of being stored for at least one
year .

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 Applied in the preparation of sunscreens.
 SLN has UV reflecting properties.

ORAL SLN IN ANTITUBERCULAR THERAPY
 Anti-tubercular drugs such as rifampicin, isoniazide,
loaded SLNs able to decrease dosing frequency and increase bioavailability.

SLN AS A GENE VECTOR CARRIER
 Several recent reports of SLN carrying genetic materials such as DNA,
plasmid DNA, & other nucleic acid have been reported.

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 Vyas S.P. and Khar R.K. Targeted And Controlled Drug
Delivery System, 1stEdition, 2002, CBS Publication;
249 - 277.

 Jain N. K., Controlled and novel Drug Delivery, 1 st edition
2001, CBS Publication; 292 - 301.

 Mukherjee S., Ray S., Thakur R.S. “ Solid lipid nanoparticles:
a modern formulation approach in drug delivery system”
Indian journal of Pharmaceutical sciences, 71(2009) 349-358.

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 Heurtault B., Saulnier P., Pech B., Proust J.E., Benoit J.P. “
Physico-chemical stability of colloidal lipid particles’’
Biomaterials 24 (2003) 4283-4300

 Feng S., Chien S. “ Chemotherapeutic engineering: application
and further development of chemical engineering principles for
chemotherapy of cancer and other diseases” Chemical
engineering science 58 (2003) 4087-4114.

 Gasco M.R. “ Lipid nanoparticles: perspectives and
challenges”Advanced drug delivery reviews, 59 (2007)
377-378.

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Nanoparticles

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Nanoparticles