**7. Membrane contactor technique**

homogeniser in order to form fine emulsions with a mean droplet size ranging between 30–

SLN suspensions are obtained using a continuous extraction method. The O/W emulsions are introduced into an extraction column from the top; simultaneously, supercritical CO2 (at constant pressure of 80 bar and temperature 35 °C) is introduced counter-currently from the

The operating pressure and temperature conditions have to be selected to minimise losses of product due to lipid and drug dissolution into the CO2 phase at maximum extraction efficiency. The residence time required for producing pure aqueous suspensions of SLN is approximately two minutes, with the product continuously removed from the bottom of the extraction

When the O/W emulsion containing the lipid and the drug is introduced into the supercritical CO2 phase, parallel processes of solvent extraction into the supercritical CO2 phase, and the inverse flux of CO2 into the emulsion droplets occurs, leading to expansion of the organic phase of the emulsion. This in turn leads to precipitation of lipid-drug material dissolved in the

100 nm.

column.

bottom [43,44] (Figure 3).

62 Application of Nanotechnology in Drug Delivery

**Figure 3.** Extraction column for emulsion with SCF in counter-current

organic phase as composite particles [44].

SLN can be produced by using a membrane contactor [45]: a proper module has been realised (Figure 4), including a Kerasep ceramic membrane (0.1, 0.2, 0.45 μm pore size), which separates the water phase, allowed to circulate tangentially to the membrane surface, and the lipid phase; the lipid phase is heated in a pressurised vessel above its melting point, conveyed through a tube to the module (Figure 5) and pressed through the membrane pores, allowing the forma‐ tion of small droplets, which are detached from the membrane pores by tangential water flow. SLN are formed after cooling of the obtained water dispersion [46].

SLN particle size depends on many process parameters: larger sizes are obtained with higher lipid phase content, reduced lipid phase pressure and aqueous cross-flow velocity. If the temperature of the aqueous phase is below the melting point of the lipid, smaller SLN are obtained: this is due to the fact that the lipid phase solidifies suddenly in the aqueous phase. Instead the SLN size decreases when the lipid temperature increases. Particle size is also highly influenced by type and concentration of surfactants added to the formulation [47].

**Figure 4.** Module for membrane contactor. A (lipid phase), B (water phase), M (porous membrane), 7 (tangential flow filtration unit).

dispersion (e.g., emulsions, liposomes, etc.); this feed is first atomised through various techniques (centrifugal, pneumatic, ultrasonic and electrostatic atomisation) to a spray form, that is put immediately into thermal contact with a hot gas, resulting in the rapid evaporation of the solvent to form dried solid particles [50]. The dried particles are then separated from the

Techniques for the Preparation of Solid Lipid Nano and Microparticles

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

65

The design may be "open cycle", when the drying gas (usually air) is not recirculated and is vented into the atmosphere. If an organic solvent is employed, a "closed cycle" layout is more suitable than an open one, since the risk of inflammability and explosion is higher in the latter

The main advantage of the spray-drying technique is the ability to manipulate and control a variety of parameters such as solvent composition, solute concentration, solution and gas flow rate, temperature and relative humidity, droplet size, etc. So the optimisation of particle characteristics can be performed in terms of size, size distribution, shape, morphology and density, in addition to macroscopic powder properties like bulk density, flowability and

However, the spray-drying process may induce degradation of some macromolecular drugs as a result of a number of factors such as thermal stress during droplet drying, high shear stress in the nozzle and peptide/protein adsorption at the greatly expanded liquid/air interface of

Sebti *et al.* have developed a spray-drying technique to produce SLM. These SLM are composed of biocompatible phospholipids and cholesterol, and can be used as a carrier or filler to deliver drugs directly to the lungs via a dry powder inhaler [52,53]. SLM are obtained by starting from an ethanolic solution of lipids and drug, which undergo to spray-drying process. Compared to other SLM production methods, spray-drying produces particles which are characterised by smaller and more homogeneous particle size distribution. However, the produced particles are not always spherical and may have convoluted surfaces, asperities and cavities. The shape

when organic feeds are heated in the presence of oxygen [51].

gas by means of a cyclone, an electrostatic precipitator or a bag filter (Figure 6).

**Figure 6.** Spray-drying apparatus

dispersibility [51].

the spray solution.

**Figure 5.** Scheme of the apparatus for producing SLN with a membrane contactor. A (lipid phase), B (water phase), 1 (pressurised vessel containing the lipid phase), 11 (thermostated bath), 12 (thermostat), 2 (nitrogen bottle), 3 (manom‐ eter), 4 (vessel containing the water phase), 41 (thermostated bath), 42 (thermostat), 5 (stirrer), 6 (pump), 7 (tangential flow filtration unit), 8-9 (manometer).
