2)       Dispersion polymerization: In which the monomer to be polymerized is emulsified in a solvent.

Figure: 16 Dispersion polymerization process


1)Double emulsion solvent evaporation:

Figure: 17Double emulsion solvent evaporation process

Figure: 18 Solvent displacement process

Figure: 19 Salting out process

The nanoparticles are generally evaluated for the following:
1)      Size and morphology
2)      Specific surface
3)      Surface charge and electrophoretic mobility
4)      Density of nanoparticles
5)      Molecular weight
6)      Nanoparticle recovery and drug incorporation efficiency
7)      In vitro release

1)      Size and morphology:
Size of nanoparticle is determined by
a)      Photon correlation spectroscopy(PCM)

b)      Electron microscopy(EM): This include
1)      Scaning electron microscopy(SEM)
2)      Transmission electron microscopy(TEM)
3)      Freez fraction electron microscopy(FFEM)

c)      Atomic force microscopy
Electron microcopy is less time consuming, FFEM give the internel morphology of particles.

TEM and FFEM provide differentiation among nanoparticle and nanocapsules and emulsion droplets.

All the particles are coated with gold as they are non-conductive (thickness of gold coat is 30-50nm). Thus determined size should be denoted as gold-coated particle size.

Atomic force microscopy(AFM) is an advanced nanoscopic technique and used for characterization of PLA nanosphere.

Mercury porositometery is use to measure size of nanoparticles.

2)      Specific surface:
Specific surface of freez dried nanoparticles is determined with sorptometer and it is calculated by using the formula:

A= 6/ D.d

A= Specific surface
D= Density
d= Diameter of the particle

3)      Surface charge and electrophoretic mobility:
Surface charge of nanoparticles can be determined by measuring the velocity of particle in an electronic field. It can also be measured as electrophoretic mobility.

The electrophoretic mobility is determined in phosphate saline buffer & human serum.

Laser Doppler anemometry or velocimetry is widely used techniques for determination of velocities.

Phosphate saline buffer (PH-7.4) reduces the charge value of nanoparticles, zeta potential can be obtained by measuring the electrophoretic mobility applying Helmholtz-Smoluchowski equation.

4)      Density of nanoparticles:
Density of nanoparticles is determined with helum or air using a gas pychnometer

5)      Molecular weight:
Molecular weight of polymer and its distribution in the matrix can be evaluated by Gel permeation chromatography.

6)      Nanoparticle recovery and drug incorporation efficiency:
Nanoparticle recovery or Nanoparticle yield can be calculated using equation:

Drug incorporation efficiency or drug content can be calculated using equation: 

7)      In vitro release:
In vitro release is determined by using dialysis diffusion cell or nodified ultrafiltration technique and phosphate buffer is used for it.

Donar and receptor chambers are  separated by milipore membrane. Donar compartment have nanoparticles along with phosphate buffer, while the receptor compartment contain only buffer solution.The receptor compartment is assayed for drug release at various time interval.

Devices used for evaluation:
The quantitative determination of exposure to nanoparticles currently poses a major challenge, because every environment already contains airborne particles in suspension. Through this mixture of dusts of different granulometries and various compositions, the content and characterization of nanoparticles must be determined. In industrial hygiene, airborne dust quantities are normally determined in units of mass per volume for most dusts, except in the case of fibres, which are counted.

These different ways of evaluating airborne dusts account for parameters improved the definition of the correlation between the health impairment risk and the exposure level.

The worker’s  exposure measurements normally are taken in the respiratory zone. Because of the rapid major variances in particulate concentration observed for nanoparticles and ultrafine particles, the direct reading devices used must react quickly. Unfortunately, no device is currently adapted to sample such particles in the respiratory zone. The existing devices capable of detecting nanoparticles and ultrafine particles are bulky and not conducive to sampling in the work environment, even at fixed stations. Major developments will be required to determine the precise occupational exposure on a routine basis with user-friendly, robust and affordable instruments.

Nanoparticles can be detected by electrostatic methods, by condensation on particles to grow them until they are measurable optically, or by other methods. Electrostatic methods require that the particles be charged and are not very sensitive, while condensation on particles is the only means allowing detection of neutral aerosol particles, which are too small to be measured by the optical method. The existing devices using condensation techniques can cover a wide range of diameters and concentrations.

The devices using the detection methods described above are often used with other devices, such as electrical mobility analyzers acting as preselectors. Combining these two types of devices obtains the granulometries or fine structures of ultrafine aerosols. Most of the devices used for nanoparticle detection cannot discriminate between nanoparticle agglomerates or single particles. This is why they are limitative in terms of assessment of aerosol toxicity, because it has been shown that nanoparticle agglomerates can have increased toxicity compared to solid particles of the same size.

A) Devices for direct measurement of concentration
Different devices and techniques allow measurement of certain parameters of particles in suspension in a liquid or gaseous medium. These parameters generally are the particulate concentration by mass, surface or number present in a certain liquid or gaseous volume. Some devices or techniques also make it possible to obtain the granulometric structure of these suspensions, that is, obtain these parameters for the different particle sizes present.

Table briefly illustrates some of these devices or techniques and their range of applicability. The following sections briefly describe the relevant nanoparticle detection techniques.

Table: 1 Techniques available for determination of size analysis

B) Diffusion batteries
Diffusion batteries are used as preselectors for detection devices, such as condensation nucleuscounters (CNC). They use the well-known phenomenon of the increase in particle diffusioncapacity in inverse proportion to the decrease in particle diameter. Small particles passingthrough a sieve will interact with it more due to surface attraction forces and will be depositedmore quickly on the neighbouring walls than coarse particles. The batteries use this phenomenonto separate the particles by granulometry brackets. This separation technique can be used forparticles ranging from 2 nm to 200 nm but is most often applied for particlessmaller than 100 nm. Granulometric resolution is limited,which explains why the devices described above, using electrostatic classification, are preferred to diffusion batteries. TSI is the only manufacturer to offer such a device with its model 3040/3041.



Subscribe to Pharmatutor Alerts by Email