Particle Size Analysis

Question 1

Why is particle size important?

Answer 1

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)

Question 2

What are the challenges with estimating particle size?

Answer 2

1) particle shape irregular

2) particle size not uniform

Question 3

How do we overcome challenges arising from particle size estimation?

Answer 3

• assume they’re all spheres

- and consider particle size distribution

Question 4

What is the size, volume and surface area of irregularly shaped particles expressed in terms of?

Answer 4

Expressed in terms of the equivalent sphere diameter

Question 5

what is perimeter diameter?

Answer 5

the diameter of an equivalent sphere with the same perimeter as the particle

Question 6

what is projected area diameter?

Answer 6

the diameter of an equivalent sphere with the same projected area as the particle

Question 7

what are two types of statistical diameters?

Answer 7

1. Feret’s diameter

2. Martins diameter

Question 8

What is Feret’s diameter?

Answer 8

the average length of the line across the width of the particle in various orientations

Question 9

what is Martin’s diameter?

Answer 9

the average length of the line bisecting the particle into equal areas (area A = area B) in various orientation

Question 10

what is hydrodynamic diameter?

Answer 10

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)

Question 11

what three factors affect the hydrodynamic diameter calculation by affecting diffusion?

Answer 11

1. ionic strength
2. surface structure
3. shape

Question 12

In a normal Gaussian distribution curve, are mean, median and mode equal or different?

Answer 12

equal

Question 13

in a bimodal distribution how many modes are there?

Answer 13

2 modes

Question 14

In a positively skewed unimodal distribution curve, what are the mean, median and modes like?

Answer 14

Mean>Median>Mode

-there are more smaller particles than there are larger ones

Question 15

In a negatively skewed unimodal distribution curve, what are the mean, median and modes like?

Answer 15

Mean

Question 16

what is monodispersity?

Answer 16

when all the particles are approximately the same size and there’s narrow particle distribution

Question 17

what is polydispersity?

Answer 17

when there’s particles of varying sizes and there’s a broad distribution of these particles

Question 18

how do we work out polydispersity index (PDI)?

Answer 18

PDI = (Standard deviation of particle size divided by mean particle size)^2

Question 19

How do you work out the span of the particle (the range of particle size)?

Answer 19

(D90-D10) divided by (D50)

Question 20

How does laser diffraction measure particle size distribution?

Answer 20

• 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)

Question 21

What is the size of the particles expressed as from the laser beam diffraction method?

Answer 21

the volume-equivalent sphere diameter

Question 22

What is Dynamic Light Scattering (DLS)?

Answer 22

• 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

Question 23

what particle size if laser diffraction suitable for?

Answer 23

0.01-3500uM

Question 24

what particle size is DLS suitable for?

Answer 24

0.3nm-10uM

so smaller particles than Laser diffraction

Question 25

What is the Stokes-Einstein equation?

Answer 25

Diffusion coefficient = (boltzmann constant x temperature) divided by (3 x pi x Diffusion medium viscosity x hydrodynamic diameter of particle)