**4. Coacervation method**

Recently, a new method was developed to prepare-in a controlled way-SLN by coacervation. This method allows the incorporation of drugs, without using very complex equipment or dangerous solvents, and is therefore inexpensive for laboratory and industrial application. It is based on the interaction between a micellar solution of a fatty acid alkaline salt (soap) and an acid solution (coacervating solution) in the presence of different amphiphilic polymeric stabilizing agents: fatty acid nanoparticles precipitate as proton exchange occurs between the coacervating solution and the soap solution [27,28].

contacting water, encapsulating the drug. Particle size can be influenced by lipid type,

Techniques for the Preparation of Solid Lipid Nano and Microparticles

http://dx.doi.org/10.5772/58405

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SLN can also be prepared starting from emulsion precursor, whose organic phase is constituted

O/W or W/O/W emulsions can be prepared: O/W emulsions are used for lipophilic drugs, that are dissolved in the inner organic phase of the system [33,34], together with the lipid. W/O/W emulsions are suitable for hydrophilic drugs, that are dissolved in the inner aqueous phase, while the lipid is dissolved in the intermediate organic phase of the multiple system [35,36].

Nanoparticles are formed when the solvent is removed either by evaporation (solvent evaporation technique for volatile solvents) [33, 35] or by water dilution (solvent diffusion technique for partially water miscible solvents) [34, 36]: owing to solvent removal lipid

Solvent evaporation technique is quite outdated and shows many drawbacks, due to the toxicity of chlorinated solvents used; solvent diffusion is more innovative and most of the

Supercritical fluid (SCF) technology has gained increasing interest in the last years for nanoparticle production. SCF is obtained above its critical pressure and temperature: above this fluid's critical point, the solubility of a substance in the fluid can be modulated by a relatively small change in pressure. Due to its low critical point at 31 °C and 74 bar, and its low

RESS, which is also called supercritical fluid nucleation (SFN), is based on a simple principle: the matrix is dissolved in SCF, which is then expanded through a nozzle, in order to form the particles [38]. This major limitation of RESS lies in the too low solubility of compounds in SCF, that precludes production at acceptable costs. In fact its applications to lipid particles is very

solvent employed show a better safety profile compared to volatile solvents.

cost and non toxicity, carbon dioxide (CO2) is the most widely used SCF [37].

The four main SCF processes used to produce nano-or microparticles are:

**1.** Rapid Expansion of Supercritical Solutions (RESS);

**4.** Supercritical Fluid Extraction of Emulsions (SFEE).

**3.** Particles from Gas-saturated Solutions/Suspensions (PGSS);

**2.** Gas Anti-Solvent (GAS) process;

**6.1. RESS**

limited.

surfactant and solvent used, and from the viscosity of the outer phase [31,32].

by a solvent, which can be either volatile or partially water miscible.

**5.2. Solvent evaporation – Diffusion from emulsions**

precipitates as nanoparticles encapsulating the drug.

**6. Supercritical fluid based methods**

In this method the precursor for SLN preparation is a soap micellar solution, obtained at a temperature above its Krafft point (that is the solubilisation temperature of the soap in water): drug can be dissolved directly in the micellar solution, or pre-dissolved in a small amount of ethanol, in order to enhance micellisation. As for microemulsion templates, the good solubil‐ ising properties of micellar solutions allow an advantageous drug loading within SLN for many drugs, especially for poorly water soluble drugs [29, 30].

The salt of fatty acid is chosen from the group consisting from sodium stearate, sodium palmitate, sodium myristate, sodium arachidate and sodium behenate in a concentration preferably between 1 and 5% w/w. The stabilizing agent is selected from the group of surface active non ionic polymers: polyvynilacetate/polyvynilalcohol and polyoxyethylene/polyoxypropylene copolymers, dextrans, hydroxypropylmethylcellulose. Normally the acidification takes place at a temperature between 40 and 50 °C, above the Krafft point of the fatty acid sodium salt; sodium arachidate and behenate need higher temperatures. Then the obtained suspension is rapidly cooled to 15 °C [27,28].

A very important feature of this method is the possibility to control the size of SLN changing the reaction conditions. In order to obtain a homogeneous and stable nanoparticle suspension, a key role is played by the right coupling between the fatty acid alkaline salt and the proper coacervating solution. Particle size is highly influenced by the lipid concentration: increasing the micellar solution concentration the SLN size increases. Also the type and the grade of the polymer used as stabiliser influence the SLN mean particle size [28].
