Particle size

Question 1

Give 5 reasons why particle size is important ?

Answer 1

1) Size influences physical properties of pharmaceutical materials
e. g: Powder flow, tablet formation
2) It tells us if a process has been successful
3) Gives us an indication of product stability
4) For QC of products; increases confidence that a product is the same as previous batches
5) Indicates in-vivo behaviour

Question 2

Define Equivalent diameters

Answer 2

The diameter of a sphere that’s in some way similar to the particles in question

Question 3

Give two examples of in-vivo particle behaviour based on particle size

Answer 3

1) Absorptive rate of insulin from IM injections -depends on particle size
2) Nanosized particles are able to accumulate in ‘leaky’ cancerous tissues via EPR effect (enhanced permeability and retention)

Question 4

Define Volume Equivalent Diameter (dV)

Answer 4

The diameter of a sphere that has the same volume as the irregular particle

Question 5

Why is Volume Equivalent Diameter( dV) a good concept for defining the size of an irregular shaped particle ?

Answer 5

It’s an unambiguous method as particles have a well defined volume

Question 6

Define ‘Cumulative Frequency representation’

Answer 6

The percentage of particles above or below a given size rather than at a given size

Question 7

Name 4 techniques that can be used to measure particle size

Answer 7

1) Sieving
2) Sedimentation
3) Microscopy
4) Light scattering

Question 8

Choice of technique chosen to measure particle size depends on ?

Answer 8

• Cost, Time taken, Skill required, Quantity of material needed, Precision

Question 9

What are sieves ?

Answer 9

Precision-woven square mesh made from steel or bronze wire

Question 10

What is the smallest particle size that’ll pass through the sieve ?

Answer 10

50 micrometers

Question 11

Explain Sieve Equivalent Diameter method

Answer 11

1) Standard size sieves are stacked into a ‘nest’ of decreasing mesh size (bottom is a closed tray)
2) Sample is put in top sieve and shaken allowing particles to fall through until mesh is too small. At this point the particles are retained
3) When shaking is completed, the amount of particles in each sieve is weighed

Question 12

State some errors in sieving

Answer 12

• Sieve holes may vary in size (due to manufacture or damage)
• Powder may coat the wired therefore reducing sieve apetures (holes)
• Particles may be cohesive so stick together and don’t pass through the mesh
• Vibration from shaking may damage the particles therefore leading to erroneous fines
• Sample may not be shaken enough to get particles to final sieve
• Sieve may be overloaded (sieving will only work for a light load)
• Particle shape may cause problems (e.g: needle like particles)

Question 13

Define Sedimentation in theory

Answer 13

The rate at which suspended particles settle

Question 14

The connection b/wn particle size and settling rate is known as

Answer 14

Sedimentation velocity

Question 15

Define Sedimentation Velocity

Answer 15

The connection b/wn particle size and settling rate

Question 16

Sedimentation Velocity isn’t directly measure in Sedimentation in practice). TRUE or FALSE

Answer 16

TRUE

Question 17

Sedimentation balance is measure in sedimentation in practice. TRUE or FALSE

Answer 17

TRUE

Question 18

Define Sedimentation balance

Answer 18

A measure of the amount of material settled in a particular time

Question 19

The amount of particles remaining in suspension vs time can be measured by ?

Answer 19

Passing a beam of light or X-rays through the sample

Question 20

Settling can be slow under gravity. TRUE or FALSE

Answer 20

TRUE

Question 21

Centrifugal sedimentation is usually used to speed up settling. TRUE or FALSE

Answer 21

TRUE

Question 22

State 3 types of microscopy

Answer 22

1) Light
2) Electron
3) Atomic force

Question 23

Explain the process of Microscopy

Answer 23

Computer analyses image, counts pixels in each region, constructs histogram and computes statistics

Question 24

Name one advantage of Microscopy

Answer 24

It is one of the few methods of getting shape information

Question 25

Name one disadvantage of Microscopy

Answer 25

It measure relatively few particles

Question 26

Name 4 advantages of Light Scattering

Answer 26

Rapid, Easy to use, Wide applicability, Wide size range

Question 27

Explain the Light scattering phenomena

Answer 27

• When we shine light through a suspension of particles, it scatters in different directions
• If we place a screen opposite the particles, we see a scattering/diffraction pattern
• This pattern is determined by particle size and shape
• The smaller the light particle, the larger the light scatter
• The bigger the light particle, the smaller the light scatter

Question 28

What 2 problems arise may from Light scattering ?

Answer 28

• Measuring the diffraction pattern

- Finding the particle size distribution from diffraction pattern

Question 29

Describe the Operation of a laser diffraction sizer

Answer 29

1) Laser light is passed through particles in dilute suspension
2) The laser light source is of high intensity, single colour and in a single direction]
3) An array detector, similar to digital camera sensor -measures the light intensity at each point

Question 30

How does the calculation of Laser diffraction sizer work ?

Answer 30

• It guesses the size distribution (the ‘trial’ distribution)
• It calculates the scattering pattern of the trial distribution
• Trail contribution of scattering pattern is compared with the measure scattering pattern
• The trial distribution is readjusted
• Scattering pattern of trial distribution is recalculated
• Trail distribution is adjusted until its scattering pattern is the same as the measured scattering pattern

-The size measured represents the hydrodynamic
radius; the size of a sphere that moves at an
identical rate to the particle

Question 31

Define Hydrodynamic radius

Answer 31

The size of a sphere that moves at an identical rate to the particle

Question 32

What instrument is used for Particle counting ?

Answer 32

Electrical zone sensing (EZS) technique aka Coulter counter

Question 33

For some applications, the amount of particles is important to know. Give examples of such applications

Answer 33

• Cell counting

- Particle contamination in injections

Question 34

Name a common problem/disadvantage b/wn Sieving, Sedimentation, Microscopy and Light Scattering

Answer 34

These methods tell you the particle size distribution but do not tell you how many particles are present

Question 35

The principle of the Hiac counter is a method used in which tests ?

Answer 35

Used in Pharmacopoeial tests for particles in injections

Question 36

Name another method of particle counting similar to EZS (electron zone sensing)

Answer 36

Optical particle counting

Question 37

Describe Optical particle counting

Answer 37

• • Particles in dilute suspension are passed through a narrow
  beam of light
• As they pass they cast a shadow which is measured by a Photodetector
• This is Hiac counter principle