Introduction to Nano Particles.

1. SEMINAR ON
SOLID LIPID NANOPARTICLES
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Presented by:
Dhiraj Shrestha
M.Pharm(Pharmaceutics)

2. Introduction
Advantages & disadvantages
Aims of SLNs
Principle of drug release
Methods of Preparation
Sterilization of SLNs
Analytical characterization of SLNs
Applications of SLNs
Routes of administration
References
CONTENTS :
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3. Solid lipid nanoparticles
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 is dissolved, entrapped, and or to which the active
principle is adsorbed or attached.
No potential toxicity problems as organic solvents are not used.
SLNs are spherical in shape & diameter range from 10-1000nm.
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To overcome the disadvantages associated with the liquid state of
the oil droplets, the liquid lipid was replaced by a solid lipid shown
in fig,
Fig. 1: Structure of solid lipid nanoparticle (SLN)

5. The reasons for the increasing interest in lipid based system are :
1. Lipids enhance oral bioavailability and reduce plasma
profile variability.
2. Better characterization of lipoid excipients.
3. An improved ability to address the key issues of technology
transfer and manufacture scale-up.
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6. Advantages of SLN
1) Control and target drug release.
2) Excellent biocompatibility.
3) Improve stability of pharmaceuticals.
4) High and enhanced drug content.
5) Easy to scale up and sterilize.
6) Enhanced bioavailability of entrapped bioactive compounds.
7) Much easier to manufacture than biopolymeric nanoparticles.
8) No special solvent required.
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7. 9) Conventional emulsion manufacturing methods applicable.
10) Raw materials essential the same as in emulsions.
11) Can be subjected to commercial sterilization procedures.
Disadvantages of SLN
1) Particle growth.
2) Unpredictable gelation tendency.
3) Unexpected dynamics of polymeric transitions.
4) Drug loading capacity is limited.
5) High pressure induce drug degradation.
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Aims of solid lipid nanoparticles
1) Possibility of controlled drug release.
2) Increased drug stability.
3) High drug pay load.
4) No bio-toxicity of the carrier.
5) Avoidance of organic solvents.
6) Incorporation of lipophilic and hydrophilic drugs.

9. Principles of drug release from SLNs
The general principles of drug release from lipid nanoparticles
are as
1. Crystallinization behaviour of the lipid carrier and high
mobility of the drug lead to fast drug release.
2. Higher surface area due to smaller particle size in nanometer
range gives higher drug release.
3. Slow drug release can be achieved when the drug is
homogenously dispersed in the lipid matrix. It depends on
type and drug entrapment model of SLN.
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10. Methods of preparation of solid lipid nanoparticles
1. High pressure homogenization
A. Hot homogenization
B. Cold homogenization
2. Ultrasonication
A. Probe ultrasonication
B. Bath ultrasonication
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SLN preparation:
General ingredients include solid lipid,emulsifier & water
Lipid contains triglicerides, partial glycerides, fatty acids, steroids,waxes.
Combination of emulsifier might prevent particle agglomeration.
Emulsifier include soybean, lecithin, egg lecithin, poloxmer etc.

11. 3. Supercritical fluid technology
4. Solvent emulsification-diffusion method
5. Microemulsion based method
6. Spray drying method
7. Precipitation technique
8. Film-ultrasound dispersion
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1. High pressure homogenization
A. Hot homogenization

13. B. cold homogenization process
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14. 2. Ultrasonication/high speed homogenization
SLNs are also prepared by ultrasonication or high speed homogenization
techniques.
For smaller particle size combination of both ultrasonication and high
speed homogenization is required
Advantages
Reduced shear stress.
Equipment used is very common.
No temperature induced drug degradation.
Disadvantages
Potential metal contamination.
Physical instability like particle growth upon storage.
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3. Supercritical fluid Technology :
SLNs can also be prepared by Rapid Expansion of
Supercritical Solution method(RESS),
Supercritical Fluid Extraction of Emulsions (SFEE).
Advantage;
 Avoidance of the use of solvents,
 Particles obtained as a dry powder instead of suspensions,
 Requires mild pressure and temperature conditions.

16. 4. Solvent emulsification-diffusion method
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17. 5. Microemulsion based method
Fig. : Microemulsion method
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18. 6. Spray drying method
It's an alternative procedure to lyophilization in order to transform
an aqueous NLC dispersion into a drug product.
It's a cheaper method than lyophilization. But his method can
cause particle aggregation due to high temperature, shear forces and
partial melting of the particle.
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19. 7. Precipitation method
The glycerides are dissolved in an organic solvent (e.g.
chloroform) and the solution will be emulsified in an aqueous phase.
After evaporation of the organic solvent the lipid will be precipitated
forming nanoparticles.
8. Film-ultrasound dispersion
lipid + drug add in to organic solutions, after decompression,
rotation and evaporation of the organic solutions, a lipid film is formed.
Then the aqueous solution which includes the emulsions was added,
Using the ultrasound with the probe to diffuser at last, the SLN with the
little and uniform particle size is formed.
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Strerilization of SLNs
For ocular and parenteral administration SLNs must be sterile.
For lecithin stabilised SLNs autoclaving is possible
& it is not applicable for sterically stabilized polymers.
Physical stability during autoclave can not be stated,
it depends on composition.
SLNs can also be sterilized by filtration.

21. 1) Measurement of particle size
Static light scattering (SLS)
Electron microscopy
Acoustic methods.
Atomic force microscopy (AFM)
DSC
Analytical characterization of SLN
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22. 2) Measurement of crystallinity & lipid modification
X-ray photoelectron spectroscopy
Laser doppler anaemometry
DSC
Gel chromatography
Electrophoresis.
DSC.
IR.
X-ray scattering.
Raman spectroscopy
3) Co – existence of additional structures
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23. Routes of administration
1. Parenteral administration
2. Oral administration
3. Rectal administration
4. Nasal administration
5. Respiratory delivery
6. Ocular administration
7. Topical administration
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24. 1. SLN as potential new adjuvant for vaccines.
2. Solid lipid nanoparticles in cancer chemotherapy.
3. Solid lipid nanoparticles for delivering peptides and proteins.
4. Solid lipid nanoparticles for targeted brain drug delivery.
5. Solid lipid nanoparticles for parasitic diseases.
6. Solid lipid nanoparticles for ultrasonic drug and gene delivery.
7. SLN applied to the treatment of malaria.
8. Solid lipid nanoparticles in tuberculosis disease.
9. SLN in cosmetic and dermatological preparations.
10. SLN for potential agriculture applications
Applications of SLN
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25. Vyas S.P. Targeted And Controlled Drug Delivery System,
1stEdition, 2009, CBS Publication;
299-321 .
Jain N. K., Controlled and novel Drug Delivery, 1st edition
2003(reprint), CBS Publication; 408-425.
International Current Pharmaceutical Journal 2012, 1(11):
384-393
Muller, R.H., Mäder, K., Gohla, S.H. (2000) Solid Lipid
Nanoparticles For Controlled Drug Delivery- A Review of the
State of the art. Eur J Pharm Bio Pharm 50(1): 161-177.
REFERENCE
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