Particle Size Analysis Flashcards
Why is particle size important?
Because particle size:
1) affects processing and handling (I.e. powder flow, compaction)
2) affects the product quality (I.e. mixing and dose uniformity)
3) Affects biopharmaceutical properties (I.e. dissolution rate)
4) affects patient acceptability (I.e texture, feel etc)
What are the challenges with estimating particle size?
1) particle shape irregular
2) particle size not uniform
How do we overcome challenges arising from particle size estimation?
- assume they’re all spheres
- and consider particle size distribution
What is the size, volume and surface area of irregularly shaped particles expressed in terms of?
Expressed in terms of the equivalent sphere diameter
what is perimeter diameter?
the diameter of an equivalent sphere with the same perimeter as the particle
what is projected area diameter?
the diameter of an equivalent sphere with the same projected area as the particle
what are two types of statistical diameters?
- Feret’s diameter
2. Martins diameter
What is Feret’s diameter?
the average length of the line across the width of the particle in various orientations
what is Martin’s diameter?
the average length of the line bisecting the particle into equal areas (area A = area B) in various orientation
what is hydrodynamic diameter?
the diameter of a hypothetically equivalent sphere that diffuses in the same way as the particle (diameter of sphere that moves (diffuses) in the same way as the particle)
what three factors affect the hydrodynamic diameter calculation by affecting diffusion?
- ionic strength
- surface structure
- shape
In a normal Gaussian distribution curve, are mean, median and mode equal or different?
equal
in a bimodal distribution how many modes are there?
2 modes
In a positively skewed unimodal distribution curve, what are the mean, median and modes like?
Mean>Median>Mode
-there are more smaller particles than there are larger ones
In a negatively skewed unimodal distribution curve, what are the mean, median and modes like?
Mean
what is monodispersity?
when all the particles are approximately the same size and there’s narrow particle distribution
what is polydispersity?
when there’s particles of varying sizes and there’s a broad distribution of these particles
how do we work out polydispersity index (PDI)?
PDI = (Standard deviation of particle size divided by mean particle size)^2
How do you work out the span of the particle (the range of particle size)?
(D90-D10) divided by (D50)
How does laser diffraction measure particle size distribution?
- particles that pass through the laser beam scatter the light
- smaller particles scatter the beam by a wider angle
- the scattered light is detected by photodetectors
- size of particles determined from the angular light intensity using mathematical models (i.e. Mie theory and Franhofer approximation)
What is the size of the particles expressed as from the laser beam diffraction method?
the volume-equivalent sphere diameter
What is Dynamic Light Scattering (DLS)?
- aka Photon Correlation Spectroscopy (PCS)
- smaller particles diffuse more rapidly
- these scattered particles interfere with laser light so laser light is scattered by their brownian motion
- fluctuating scattered light intensities produced at photodetectors
- fluctuating patters relate to the velocity of the particles
- diffusion coefficient of these particles computed from the fluctuations
- hydrodynamic diameter determined using Stokes-Einstein equation
what particle size if laser diffraction suitable for?
0.01-3500uM
what particle size is DLS suitable for?
0.3nm-10uM
so smaller particles than Laser diffraction
What is the Stokes-Einstein equation?
Diffusion coefficient = (boltzmann constant x temperature) divided by (3 x pi x Diffusion medium viscosity x hydrodynamic diameter of particle)
