5. Why SLN ?
Conventional o/w emulsion
protection of drug against chemical degradation is required. Hence,
Incorporation of drug in the solid lipid matrix surely offer a better
protection.
Prolonged release of drug from emulsion is not feasible which can be
achieved to a certain extent from SLN.
Polymeric nanoparticles:
Lower cytotoxicity of SLN due to the absence of solvents.
Low cost of excipients.
Large scale production is possible by the simple process of high-
pressure homogenization
6. In comparison with liposomes SLNs offer better protection to drug
against chemical degradation.
However there are certain limitations associated with SLN, like
limited drug loading capacity and drug expulsion during storage,
which can be minimized by the next generation of solid lipids,
Nanostructured lipid carriers (NLC).
NLC are lipid particles with a controlled nanostructure that
improves drug loading and firmly incorporates the drug during
storage .
Owing to their properties and advantages, SLN and NLC may find
extensive application in topical drug delivery, oral and parental
administration of cosmetic and pharmaceutical actives.
Cosmeceuticals is emerging as the biggest application target of
7. PREPARATION OF SLNs
• SLNs are made up of solid lipid, emulsifier and water/solvent.
• The lipids used: triglycerides (tri-stearin), partial
glycerides(Imwitor), fatty acids (stearic acid, palmitic acid),
steroids (cholesterol) and waxes (cetyl palmitate).
(Imwitor is blend of mono, di and tri-glycerides especially of capryllic
and caproic acids.)
• Various emulsifiers and their combination (Pluronic F 68, F 127)
have been used to stabilize the lipid dispersion. The combination
of emulsifiers might prevent particle agglomeration more
efficiently and hence helps in dispersion.
(pluronic f 123 is triblock co polymer of polyethylene glycol and
propylene glycol)
8. Preparation methods:-
1. High shear homogenization:
• Used for the production of solid lipid nanodispersions
• Method is easy to handle. Dispersion quality is often compromised by the
presence of micro particles.
• Different parameters which affect the process include emulsification time,
stirring rate and cooling condition & also the particle size are investigated by
Olbrich et al.
• Lipids: tripalmitin, mixture of mono, di, triglycerides (WitepsolW35) with
glycerol bahenate and poloxamer 188 used as steric stabilizers or emulsifiers
(0.5% w/w). Witepsol W35 on dispersion, the best SLN quality was obtained
after stirring for 8 min at 20,000 rpm followed by cooling 10 min and stirring at
5000 rpm at a room temperature.
Higher stirring rates did not significantly change the particle size, but slightly
improves the Dispersion.
9. 2. Hot homogenization:
• Carried out at temperature above the melting point of the lipid and is
similar to homogenization of emulsion
• Typically lipid content is between 5-10%. By this method up to 40%
success is obtained. A pre-emulsion of the (drug loaded) lipid melt and
the aqueous emulsifier phase (same temperature) is obtained by high-
shear mixing device.
• High pressure homogenization of the pre-emulsion is done above the lipid
melting point.
• The quality of the pre-emulsion affects the quality of the final product to a
great extent and it is desirable to obtain droplets in the size range of a few
micrometers.
10. • Lower particle sizes are obtained at higher processing temperatures
due to lower viscosity of the lipid phase. Good product is obtained due
to several passes through the high-pressure homogenizer (HPH),
typically 3-5 passes.
• High pressure processing always increases the temperature of the
sample. In most cases 3-5 homogenization cycles at 500-1500 bar are
sufficient. Problem: High temp. may lead to degradation of the active
compound.
11. 3. Cold homogenization:
• This method has been developed to overcome the problems of the hot
homogenization technique such as: Temperature mediated accelerated
degradation of active compound.
• First step in between cold and hot homogenization is same but they are
differing from next steps. The lipid melt is cooled rapidly using ice or
liquid nitrogen (for distribution of drug in the lipid matrix).
• Particle sizes attained are in the range 50-100 microns. Compared to
hot homogenization; larger particle sizes and a broader size distribution
are typical of cold homogenized samples.
• Cold homogenization minimizes the thermal exposure of the sample.
12. 4. Ultrasonication or high speed homogenization:
• SLNs can also be produce by sonication or high speed stirring.
• It is very simple and it can be advantageous over other method like hot
and cold homogenization because the equipment used in this
technique is very common in every lab.
• Disadvantage is non uniform size distribution and physical instability of
active compound like particle growth upon storage and also metal
contamination due to ultrasonication.
13. 6. SLN prepared by solvent emulsification/evaporation: (mostly
considering drug delivery)
• The lipophilic material is dissolved in water immiscible organic solvent
(cyclohexane) that is emulsified in an aqueous phase. Upon
evaporation of the solvent nanoparticle, dispersion is formed by
precipitation of the lipid in the aqueous medium.
• The mean diameter of the obtained particles was 25 nm with
cholesterol acetate (as a model drug) and lecithin/sodium
glycocholate blend as emulsifier.
• The reproducibility of the result was confirmed by Siekmann et.al. ,
who produced the cholesterol acetate nanoparticles of mean size 29
nm.
16. REFERENCES
• Solid Lipid Nanoparticles: A Modern Formulation Approach in Drug
Delivery System
S. MUKHERJEE*, S. RAY AND R. S. THAKUR
• Solid Lipid Nanoparticles: Technological Developments and in Vivo
Techniques to Evaluate Their Interaction with the Skin
Mariella Bleve, Franca Pavanetto and Paola Perugini
Department of Drug Sciences, University of Pavia
• SOLID LIPID NANOPARTICLES AS COLLOIDAL DRUG CARRIER
SYSTEMS
António J. Almeida
