Dynamic light scattering (DLS) techniques have been the mainstay for the determination of particle size and particle size distributions. When light is directed at a particle, it can either be deflected or absorbed by the particle, which is dependent on the size of the particle relative to the wavelength of the light.
Sample Preparation for Dynamic Light Scattering
Particles are presented, suspended in a liquid of known viscosity. Mechanical agitation/sonication may be required to achieve adequate dispersion of particles.
Principle of Dynamic Light Scattering
In dynamic light scattering (DLS), also called photon correlation spectroscopy and quasielastic light scattering, the intensity of scattered light at a given angle is measured as a function of time for a population of particles. The rate of change of the scattered light intensity is a function of the movement of the particles by Brownian motion. Brownian motion is the random movement of a small particle or macromolecule caused by collisions with the smaller molecules of the fluid in which it is suspended. It is independent of external variations, except the viscosity of the suspending fluid and its temperature, and as it randomizes particle orientations, any effects of particle shape are minimized.
Brownian motion is independent of the suspending medium, and although an increase in the viscosity does slow down the motion, the amplitude of the movements is unaltered. Because the suspended, small particles are always in a state of motion, they undergo diffusion. Diffusion is governed by the mean free path of a molecule or particle, which is the average distance of travel before diversion by collision with another molecule.
DLS analyses the constantly changing patterns of laser light scattered or diffracted by particles undergoing Brownian motion, and monitors the rate of change of scattered light during diffusion. In most instruments, monochromatic light from a helium–neon laser is focused onto the measurement zone, containing particles dispersed in a liquid medium. Light is scattered at all angles, and is often detected by a detector placed at an angle of 90°, although other angles may be chosen, depending on the instrument used. The detection and spatial resolution of the fluctuations in the intensity of the scattered light, are used to calculate size distribution.
Brownian diffusion causes three-dimensional random movement of particles, where the mean distance travelled, , does not increase linearly with time, t, but according to the following relationship:
$$ \overset-x=\sqrt{Dt} $$
where D is the diffusion coefficient.
This equation, known as the Stokes–Einstein equation, is the basis for calculating particle diameters by DLS:
$$ D=\frac{1.38\times10^{-12}T}{3{\mathrm{πηd}}_{\mathrm h}}m^2s^{-1} $$
where dh is the hydrodynamic diameter, η the fluid viscosity and T the absolute temperature (kelvins).
This calculation assumes that particles are spherical, and a very low particle concentration is required. The technique determines the hydrodynamic diameter. As colloidal particles in a liquid dispersion have an adsorbed layer of ions/molecules from the dispersion medium that moves with the particles, the hydrodynamic diameter is larger than the physical size of the particle. Most instruments also yield a polydispersity index (PDI), determined by cumulant analysis as described in the international standard on particle size analysis by DLS.
The PDI, a dimensionless term, gives information regarding the width of the size distribution, with values ranging between 0 and 1. For monodisperse samples, the PDI is theoretically zero, although values from 0 to 0.08 are taken as indicative of nearly monodisperse systems, whilst values from 0.08 to 0.2 represent particles having a relatively narrow size distribution.
Available instruments differ according to their ability to characterize different particle size ranges, produce complete size distributions, measure dispersions of both solid and liquid particles and determine the molecular weights of macromolecules. Some instruments combine DLS to determine particle size with electrophoretic light scattering to measure the electrophoretic movement of dispersed particles. The velocity of particles moving between two electrodes is measured by laser Doppler velocimetry and can be used to determine their zeta potential.
Reference:
- Aulton, M. (2018). Aulton’s pharmaceutics, the design and manufacture of medicines. Edinburgh. : Elsevier
- Khar, R.,Vyas, S., Ahmad, F., & Jain, G. (2016). Lachman/Lieberman’s The Theory and Practice of Industrial Industrial Pharmacy. New Delhi, ND: CBS Publishers & Distributors Pvt Ltd
