Particle size measurement photon correlation spectroscopy

The International Standard ISO 13321 1996 Particle size analysis - Photon correlation spectroscopy (PCS) , provides for methods of validation as well as good general advice on the use of this method. This standard is being amended to include frequency analysis techniques as well as addressing measurements at concentrations greater than very dilute. 

Various techniques and equipment are available for the measurement of particle size, shape, and volume. These include for microscopy, sieve analysis, sedimentation methods, photon correlation spectroscopy, and the Coulter counter or other electrical sensing devices. The specific surface area of original drug powders can also be assessed using gas adsorption or gas permeability techniques. It should be noted that most particle size measurements are not truly direct. Because the type of equipment used yields different equivalent spherical diameter, which are based on totally different principles, the particle size obtained from one method may or may not be compared with those obtained from other methods. 

PVA and TaM -for the 88%-hydrolyzed PVA. The same dependence was found for the adsorbed layer thickness measured by viscosity and photon correlation spectroscopy. Extension of the adsorption isotherms to higher concentrations gave a second rise in surface concentration, which was attributed to multilayer adsorption and incipient phase separation at the interface. The latex particle size had no effect on the adsorption density however, the thickness of the adsorbed layer increased with increasing particle size, which was attributed to changes in the configuration of the adsorbed polymer molecules. The electrolyte stability of the bare and PVA-covered particles showed that the bare particles coagulated in the primary minimum and the PVA-covered particles flocculated in the secondary minimum and the larger particles were less stable than the smaller particles. 

The adsorbed layer thickness for the llOOnm-size particles could not be measured by photon correlation spectroscopy because of the lOOOnm upper limit of this instrument. Again, the agreement between the two methods is excellent. It is interesting that the adsorbed layer thickness increases with increasing latex particle size and that these values vary with the 0.5 power of the particle radius, i.e., where R is the particle radius. This re-... 

Photon correlation spectroscopy A technique for measuring the size of submicrometer particles by analyzing their size-dependent scattering of laser light. 

The mean particle diameter was measured by photon correlation spectroscopy (PCS) with a Nanosizer N4 (Coultronics, Margency, France). The size and polydispersity of AmB lipid preparations depended on both the AmB/phospholipids ratio and the phospholipid composition. At a DMPC/DMPG molar ratio of 7/3, when the AmB content was below 10% w/w, large poly disperse particles were formed. At AmB ratios of 20% to 50% of total weight of phospholipids, a majority of submicronic particles were obtained. The smallest size, around 300 nm, and minimal polydispersity were achieved with AmB at 35% w/w that... 

Methods for analysis of the particle size distribution in the aerosol cloud include techniques such as time of flight measurement (TOE), inertial impaction and laser diffraction. Dynamic light scattering (photon correlation spectroscopy) is confined to particles (in suspension) in the submicron range. In addition to the size distribution, the particle velocity distribution can be measured with the Phase Doppler technique. 

Allen T., Photon correlation spectroscopy, in Particle Size Measurement, Vol. 1, Allen T., ed.. Chapman Hall, London, 1997, 426. 

This section contains a general description of the principles by which the Coulter Model N4 Sub-Micron Particle Analyzer, used in this study to characterize artificial gas-in-water emulsions (see Section 10.4), determines sample particle size. The measuring principles are based on the theory of Brownian motion and photon correlation spectroscopy (ref. 464,465 see also Sections 10.2 and 10.4). 

The expansion characteristics of carboxylic latex particles have been measured using three independent techniques sedimentation, which uses the change in particle density due to swelling to determine the change in particle size viscometry, which measures volume changes and photon correlation spectroscopy, which measures the diffusion coefficient of the particles. The sedimentation technique offers precise measurements at low shear but requires relatively... 

The surface charge of particles in a liquid medium can also be adjusted through the selective use of surfactants. Whether through the use of pH adjustment or surfactants, one must always ensure that the solubility of the powder does not increase, thereby dissolving the particles. Commercial instruments are readily available for this technique. The same apparatus often performs particle size measurements using photon correlation spectroscopy, which is discussed in a following section. 

Photon correlation spectroscopy (PCS), also referred to as dynamic light scattering, is a technique that is used to measure particles in the size range of 1 -0.001 p,m. Unlike particle sizing by laser diffraction, the sample, dispersed in a diluent, is not circulated, stirred, or sonicated during the measurement. The technique is dependent upon a stable suspension of particles that are in constant random motion due to collisions with molecules of the suspending liquid. 

Each of the aforementioned techniques is capable of measuring powder that would be used in low-dose, solid oral dosage formulations. The technique must be compatible with the drug substance, and must be capable of producing the information that is needed. For example, if the particle size distribution is needed to ensure dose content uniformity, photon correlation spectroscopy can only provide an average particle size. In this instance, laser diffraction or image analysis would be more suitable techniques. Table 13.1 contains a comparison of the techniques that have been discussed. 

Beside of the progress in the theory of a particle movement in the zetameter measurement cell, there was progress in particle measurement techniques. New models of zetameters enable automatic measurement of electrophoretic mobility on the basis of the shift of light wave scattered on the particle that moves in the electric field [82]. This technique is called photon correlation spectroscopy (PCS). To increase the sensitivity of the measurement, it is supported by multiangle electrophoretic light scattering (ELS). This combination, allows one also to measure the particle size distribution of the dispersed phase [83]. 

The diffusion coefficient for a suspension of monosized particles can be measured directly by photon correlation spectroscopy [12] (quasielastic light scattering). For distributions of different particle sizes, the average diffusion coefficient is determined by photon correlation spectroscopy. 

The original Acoustosizer used a single frequency whereas a later development has a range of 13 frequencies between 0.3 and 13 MHz. This allows the measurement of the dynamic mobility spectrum and the determination of the zeta potential and particle size. In order to invert the mobility spectrum into a size distribution a log-normal distribution of particle size is assumed. A comparison with photon correlation spectroscopy for determining particle size and laser Doppler anemometry for particle charge eonfirmed the results using ACS [266]. These and additional sedimentation measurements confirmed that changes in particle size and zeta potential due to dilution effects are likely to occur in aqueous and non-stabilized systems. 

In this model, the buoyant mass is then the sum of the buoyant mass of the three components, assuming that these are independent of the mass of solvent occupied in the solvation shell. Thus, the mass of the adsorbed shell can be calculated if information about the mass and density of the core particle and the density of the macromolecule and solvent are known. Photon correlation spectroscopy, electron microscopy, flow FFF, or other sizing techniques can readily provide some independent information on the physical or hydrodynamic particle size, and pycnometry can be used to measure the densities of the colloidal suspension, polymer solution, and pure liquid. 

---