**11. Spray congealing**

is influenced by the drying rate, the surface tension and the viscosity of the liquid which

In a general process, a solution of the matrix, which constitutes the particles, is contained in a syringe, with a metal capillary connected to a high-voltage power supply, working as an electrode. A metal foil collector is placed opposite the capillary as a counter electrode (Figure 7). Depending on the properties of the liquid, the flow rate and the voltage applied can be

The cone-jet mode is the method used to prepare nanoparticles, in which liquid emerging at the nozzle forms hemispherical drops because of the surface tension. By increasing the electrical field, the hemispherical drops can be changed to a conical shape, which breaks up into highly charged droplets. By selecting suitable conditions, droplets can be produced with a close size distribution and nano-or micrometer size range. Particles can be formed by evaporating the solvent from the droplets produced travelling through the electrical field.

The electrospray method has been employed to prepare monodisperse lipid-based nano-and microparticles: lipid has been dissolved in aliphatic alcohols and this solution has been used for particles production. Particle shape and size depend on the solvent and excipients used

constitutes the liquid feed.

66 Application of Nanotechnology in Drug Delivery

and on the applied voltage [54,55].

**Figure 7.** Scheme of electrospray apparatus

**10. Electrospray**

modulated.

In the spray congealing technique, lipids are heated to a temperature above their melting point and the drug is dissolved or suspended into the melted lipid. The hot mixture is then atomised through a pneumatic nozzle into a vessel, where the atomised droplets can solidify in the form of microparticles [56]. In this technique some variations can be performed, especially in the atomisation device.

The Wide Pneumatic Nozzle (WPN) (Figure 8A) is an innovative external mixing atomiser: the molten fluid and the atomisation air get in contact outside the nozzle; the former is delivered to the orifice by the Venturi effect, while the latter is delivered in radial direction with respect to the molten fluid. The atomisation occurs where the air input converges with the molten fluid [57].

The Air Pressure Nozzle (APN) (Figure 8B) is an internal mixing device: the molten fluid and the atomisation air get in contact in the mixing chamber inside the nozzle. The swirling fluid impinges on the plate and the interaction between the fluid and the air creates extreme turbulence in the chamber, and then flows through an orifice, where the droplets are exposed to shear forces, before coming in contact with a circular deflector ring and leaving the nozzle as a finely atomised spray cone [57].

**Figure 8.** A) Diagram of the external-mixing WPN. B) Diagram of the internal mixing APN

Another particular type of atomiser is based on ultrasounds [58]. The ultrasound-atomiser basically consists of three parts (Figure 9):


The atomiser is also provided of an inductive coil to keep the sonotrode at suitable temperature.

The melted lipid mixture, fed to the sonotrode by a thermostated reservoir through a funnel, is atomised by ultrasound energy into small droplets that fall freely and solidify by cooling at room temperature in a collector.

Toxicological issues are also very important: the materials used must be biocompatible and biodegradable, while the use of solvents can be a relevant drawback, since they can remain in

Techniques for the Preparation of Solid Lipid Nano and Microparticles

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

69

From a technological point of view, the possibility to scale up the process is very important, but also the feasibility of the method is relevant: in fact the use of expensive and complex

Finally the drug entrapment is very important: nowadays more and more complex molecules are entrapped within solid lipid particles. These molecules have different physico-chemical properties (solubility, hydrophobicity, etc.) and stability issues (temperature, pH, etc.). The chosen preparation technique should be the most suitable to enhance drug loading and encapsulation efficiency within the nanoparticles, without hampering the chemical stability of the molecule itself: the working temperatures and operating conditions used to prepare the

In Table 2 some important parameters, like particle size, solvents used, instrumentation needed, working temperatures and operating conditions, of the various techniques are shown

50-1000 nm High pressure

50-1000 nm High shear

**Instrumentation needed**

homogeniser

homogeniser

Ultrasound apparatus

homogeniser

**Working temperature**

5-10°C upon lipid mp

5-10°C upon lipid mp

5-10°C upon lipid mp

5-10°C upon lipid mp

lipid mp

40-75°C, according to the lipid matrix

25°C

**Operating conditions**

cavitation forces

Ultrasound treatment

pH shifts

traces in the final product.

for comparative purposes.

Coacervation 200-1000 nm

Solvent injection 100-500 nm

High pressure homogenisation

High shear homogenisation

Ultrasound homogenisation

machine can hamper the production on lab scale.

particles can affect the physico-chemical stability of the drug.

**Technique Particle size Solvent used**

50-1000 nm

Melt dispersion 1-250 μm High shear

PIT 30-100 nm 90°C

Microemulsion dilution 50-800 nm 5-10°C upon

Microemulsion cooling 50-300 nm 37-55°C

Ethanol, acetone, isopropanol

**Figure 9.** Scheme of the ultrasonic atomiser (not in scale): (A) ultrasound generator; (B) booster; (C) sonotrode; (D) inductive coil; (E) supply funnel; (F) cylindrical chamber (collector).

Another variant of the spray congealing method is to use a rotating disc [59]. With this technique, the melted mixture is dropped onto a high-speed rotating disc. The rotation induces the molten mixture to spread between the disc periphery and the cooled surface on which microparticles are collected.

Owing to this technique SLM with particle size ranging from 50 to 2000 μm can be produced.
