Solid Lpid Nanoparticles (SLN) Manufacturing 

There are several technique or method to prepare Solid lipid nanoparticles (SLN), they are:
1. High shear homogenization
2. Hot homogenization
3. Cold homogenization
4. Ultrasonication or high speed homogenization
5. solvent emulsification/evaporation method
6. supercritical fluid method
7. Spray drying method
8. Double emulsion method



Solid Lipid Nanoparticles Technique - High shear homogenization

High shear homogenization technique were initially used for the production of solid lipid Nanodispersions. But, dispersion quality is often compromised by the presence of micro particles. High-speed homogenization method is used to produce SLN by melt emulsification.

Parameters influence in SLN preparation by high shear homogenization :
• emulsification time
• stirring rate
• cooling condition on the particle size
• zeta potential

Lipids used in this method are :
• trimyristin
• tripalmitin,
• a mixture of mono, di and triglycerides (Witepsol W35, Witepsol H35) with glycerol behenate
• poloxamer 188 used as steric stabilizers (0.5% w/w).

The best SLN quality for Witepsol W35 dispersions was obtained after stirring for 8 min at 20,000 rpm followed by cooling 10 min and stirring at 5000 rpm at a room temp.

The best conditions for Dynasan116 dispersions were a 10-min emulsification at 25,000 rpm and 5 min of cooling at 5,000 rpm in cool water (≈160). Higher stirring rates did not significantly change the particle size, but slightly improved the polydispersity index.


Solid Lipid Nanoparticles Technique - Hot homogenization

Hot homogenization is done at temperatures above the lipid melting point and is similar to the homogenization of an emulsion. A pre-emulsion of the drug loaded lipid melt and the aqueous emulsifier phase at the same temperature is obtained by high-shear mixing device.

It is best to obtain droplets in the size range of a few micrometers. Higher processing temperatures gets lower particle sizes because of lowered viscosity of the lipid phase, but higher temperature may accelerate drug and carrier degradation.

To obtain better products several passes through the high-pressure homogenizer (HPH) is necessary, typically 3-5 passes. High pressure processing increases the temperature of the sample (approximately 10° at 500 bar). In most cases, 3-5 homogenization cycles at 500-1500 bar are sufficient. Increasing the homogenization leads to an increase of the particle size due to particle coalescence, this occurs because of the high kinetic energy of the particles.


Solid Lipid Nanoparticles Technique - Cold homogenization


Cold homogenization developed to overcome the problems at hot homogenization technique:
• Temperature mediated accelerated degradation of the drug payload
• Partitioning and hence loss of drug into the aqueous phase during homogenization
• Uncertain polymorphic transitions of the lipid due to complexity of the crystallization step of the nanoemulsion leading to several modifications and/or super cooled melts.

Cold homogenization process is done with the solid lipid and milling of a suspension at elevated pressure. To ensure the solid state of the lipid during homogenization, effective temperature regulation is needed.
1. solubilization or dispersion of the drug in the lipid melt.
2. The drug containing melt is cooled rapidly (using dry ice or liquid nitrogen) to favor homogenous drug distribution in the lipid matrix.
3. the drug containing solid lipid is pulverized to micropaticles by ball/mortar milling. Typical particle sizes attained are in the range 50-100 microns.
4. Chilled processing further facilitated particle milling by increasing the lipid fragility.
5. The SLNs are dispersed in a chilled emulsifier solution.
6. The dispersion is subjected to high pressure homogenization at or below room temperature with appropriate temperature control keeping in view the usual rise in temperature during high pressure processing.

Compared to hot homogenization, larger particle sizes and a broader size distribution are typical of cold homogenized samples. The method of cold homogenization minimizes the thermal exposure of the sample, but it does not avoid it due to the melting of the lipid/drug mixture in the initial step.

Continue in  METHOD OF SOLID LIPID NANOPARTICLES (SLN) PREPARATIONS (PART II)

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Solid Lipid Nanoparticles : New Pharmaceutical Delivery System

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