INTRODUCTION:

Solid lipid nanoparticles (SLN) are introduced in the year of 1991 an alternative carrier system. Tradition colloidal carriers system such as - emulsions, liposome’s and polymeric micro – and nanoparticles. Hence nanoparticles made from solid lipids are attracting major attention as novel colloidal drug carrier system for intravenous applications also they have been proposed as an alternative particulate carrier system. SLN are sub-micron colloidal carriers ranging from 50 to 1000 nm, which are composed of physiological lipid, dispersed in water or in aqueous surfactant solution. Solid lipid nanoparticle offer unique properties such as very small size, large surface area, high drug loading and the interaction of phases at the interface and are attractive for their potential to increase performance of pharmaceuticals.

Solid lipid nanoparticles are one of the modern potential colloidal carrier system as alternative materials to excipients which is identical to oil in water emulsion for parenteral nutrition. They have many advantages such as good biocompatibility, low toxicity and lipophilic drugs are better delivered by solid lipid nanoparticles and the system is physically stable.

Advantages of SLN ^1-4

• Control or target drug release.

• Good biocompatibility.

• Increase stability of pharmaceuticals.

• High and enhanced drug content.

• Easy to scale up and sterilize.

• Better control over release kinetics of encapsulated compounds.

• Improved bioavailability of entrapped bioactive compounds.

• Chemical protection of labile incorporated compounds.

• More easier to manufacture than biopolymeric nanoparticles.

• No need of any special solvent.

• Conventional emulsion manufacturing methods applicable.

• Raw materials essential the same as in emulsions.

• Very high long-term stability.

• Application versatility.

• Can be subjected to commercial sterilization procedures.

Disadvantages of SLN ^{4, 6}

• Particle growth.

• Unpredictable gelation tendency.

• Unexpected dynamics of polymeric transitions.

Aims of solid lipid nanoparticles ^{6, 9}

• Possibility of controlled drug release.

• Improve drug stability.

• High drug pay load.

• No bio-toxicity of the carrier.

• Avoidance of organic solvents.

• Incorporation of lipophilic and hydrophilic drugs.

Methods of preparation of solid lipid nanoparticles^1-10:

1. High pressure homogenization

A. Hot homogenization

B. Cold homogenization

2 . Solvent evaporation method

4. Solvent emulsification-diffusion method

5. Supercritical fluid method

6. Micro emulsion based method

7. Spray drying method

8. Double emulsion method

9. Precipitation technique

10. Film-ultrasound dispersion

1. High pressure homogenization (HPH):

It is a easy and powerful technique, which is used for the formulation of SLNs. High pressure Homogenizers push a liquid with high pressure (100–2000 bar) through a narrow gap (in the range of a few microns). The fluid rotate on a very short distance to very high velocity (over 1000 Km/h). Very high shear stress and cavitation forces disrupt the particles down to the submicron range. Generally 5-10% lipid content is used but up to 40% lipid content has also been investigated. Two general approaches of HPH are hot homogenization and cold homogenization; work on the same principle of mixing the drug in bulk of lipid melt.

A. Hot homogenization:

Hot homogenization is carried out at temperatures above the melting point of the lipid and can therefore be regarded as the homogenization of an emulsion. A pre-emulsion of the drug loaded lipid melt and the aqueous emulsifier phase (same temperature) is obtained by high-shear mixing device. HPH of the pre-emulsion is carried out at temperatures above the melting point of the lipid. generally, higher temperatures result in lower particle sizes due to the decreased viscosity of the inner phase. However, high temperatures increase the degradation rate of the drug and the carrier. Increasing the homogenization pressure or the number of cycles often results in an improve of the particle size due to high kinetic energy of the particles.

Drug in melted lipid

Dispersion of liquid phase to aqeuous mixture

Pre-emulsion

High Pressure

Hot o/w nanoemulsion

Cooling at room

Solid lipid nanoparticle

B. Cold homogenization:

Cold homogenization has been formulated to overcome various problems associated with hot Homogenization such as: Temperature-induced drug degradation, drug distribution into the aqueous phase during homogenization, Complexity of the crystallization step of the nanoemulsion leading to several modifications and/or super cooled melts. In this technique the drug containing lipid melt is cooled, the solid lipid ground to lipid micro particles and these lipid micro particles are dispersed in a cold surfactant solution yielding a pre-suspension. Then this pre-suspension is homogenized at or below room temperature, the gravitation force is strong enough to break the lipid micro particles directly to solid lipid nanoparticles.

Advantages:

· Low capital cost.

· Demonstrated at lab scale.

Disadvantages:

· Energy intensive process.

· Demonstrated at lab scale Bimolecular damage.

3. Solvent evaporation:

SLNs can also prepared by solvent evaporation method. The lipophilic material is dissolved in a Water immiscible organic solvent (e.g. cyclohexane) that is emulsified in an aqueous phase. Upon evaporation of the solvent, nanoparticles dispersion is formed by precipitation of the lipid in the aqueous medium by giving the nanoparticles of 25 nm mean size. The solution was emulsified in an aqueous phase by high pressure homogenization. The organic solvent was removed from the emulsion by evaporation under reduced pressure (40–60 mbar).

Advantages:

· Scalable.

· Mature technology.

· Continuous process.

· Commercially demonstrated

5. Supercritical fluid method:

This is an alternate method of preparing SLNs by particles from gas saturated solutions (PGSS).

Advantages:

· Avoid the use of solvents.

· Particles are obtained as a dry powder, as an alternative of suspensions.

· Mild pressure and temperature specification.

· Carbon dioxide solution is the good choice as a solvent for this method.

6. Microemulsion based method

Microemulsion method is based on the dilution of microemulsions. Basically micro-emulsions are two-phase systems contain of an inner and outer phase (e.g. o/w microemulsions). These are made by stirring an optically transparent mixture at 65-70°C, which typically composed of a low melting fatty acid (e.g. stearic acid), an emulsifier (e.g. polysorbate 20), co-emulsifiers (e.g. butanol) and water. The hot microemulsion is dispersed in cold water (2-3°C) under stirring. SLN dispersion can be used as granulation fluid for transferring in to solid product (tablets, pellets) by granulation process, but in case of low particle content too much of water needs to be removed. High-temperature gradients facilitate rapid lipid crystallization and prevent aggregation. Due to the dilution step; achievable lipid contents are considerably lower compared with the HPH based formulations.

Advantages:

· Low mechanical energy input.

· Theoretical stability.

Disadvantage:

· Extremely sensitive to change.

· Labor intensive formulation work.

· Low nanoparticle concentrations.

7. Spray drying method ⁸:

Spray drying method is an alternative technique to the lyophilization process. This recommends the use of lipid with melting point more than 70oC. The best results were obtained with SLN concentration of 1% in a solution of trehalose in water or 20% trehalose in ethanol-water mixture.

8. Double emulsion method:

Here the drug is encapsulated with a stabilizer to prevent the partitioning of drug in to external water phase during solvent evaporation in the external water phase of w/o/w double emulsion.

9. 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.

10. Film-ultrasound dispersion:

The lipid and the drug were put into suitable 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.

CONCLUSION:

Advantages of SLN contain the composition (physiological compounds), the rapid and effective production process including the possibility of large scale production, the avoidance of organic solvents and the possibility to produce carriers with higher encapsulation efficiency. Disadvantages include low drug-loading capacities, the presence of alternative colloidal structures (micelles, liposomes, mixed micelles, drug nanocrystals), the complexity of the physical state of the lipid (transformation between different modifications) and the possibility of super cooled melts which cause stability problems during storage or administration (gelation, particle size increase, drug expulsion). SLN are very complex systems with clear advantages and disadvantages to other colloidal carriers.

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Received on 26.04.2016 Modified on 21.05.2016

Res. J. Pharm. Dosage Form. & Tech. 2016; 8(3): 218-220.

DOI: 10.5958/0975-4377.2016.00030.6