Particle size Flashcards
Give 5 reasons why particle size is important ?
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
Define Equivalent diameters
The diameter of a sphere that’s in some way similar to the particles in question
Give two examples of in-vivo particle behaviour based on particle size
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)
Define Volume Equivalent Diameter (dV)
The diameter of a sphere that has the same volume as the irregular particle
Why is Volume Equivalent Diameter( dV) a good concept for defining the size of an irregular shaped particle ?
It’s an unambiguous method as particles have a well defined volume
Define ‘Cumulative Frequency representation’
The percentage of particles above or below a given size rather than at a given size
Name 4 techniques that can be used to measure particle size
1) Sieving
2) Sedimentation
3) Microscopy
4) Light scattering
Choice of technique chosen to measure particle size depends on ?
- Cost, Time taken, Skill required, Quantity of material needed, Precision
What are sieves ?
Precision-woven square mesh made from steel or bronze wire
What is the smallest particle size that’ll pass through the sieve ?
50 micrometers
Explain Sieve Equivalent Diameter method
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
State some errors in sieving
- 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)
Define Sedimentation in theory
The rate at which suspended particles settle
The connection b/wn particle size and settling rate is known as
Sedimentation velocity
Define Sedimentation Velocity
The connection b/wn particle size and settling rate
Sedimentation Velocity isn’t directly measure in Sedimentation in practice). TRUE or FALSE
TRUE
Sedimentation balance is measure in sedimentation in practice. TRUE or FALSE
TRUE
Define Sedimentation balance
A measure of the amount of material settled in a particular time
The amount of particles remaining in suspension vs time can be measured by ?
Passing a beam of light or X-rays through the sample
Settling can be slow under gravity. TRUE or FALSE
TRUE
Centrifugal sedimentation is usually used to speed up settling. TRUE or FALSE
TRUE
State 3 types of microscopy
1) Light
2) Electron
3) Atomic force
Explain the process of Microscopy
Computer analyses image, counts pixels in each region, constructs histogram and computes statistics
Name one advantage of Microscopy
It is one of the few methods of getting shape information
Name one disadvantage of Microscopy
It measure relatively few particles
Name 4 advantages of Light Scattering
Rapid, Easy to use, Wide applicability, Wide size range
Explain the Light scattering phenomena
- 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
What 2 problems arise may from Light scattering ?
- Measuring the diffraction pattern
- Finding the particle size distribution from diffraction pattern
Describe the Operation of a laser diffraction sizer
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
How does the calculation of Laser diffraction sizer work ?
- 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
Define Hydrodynamic radius
The size of a sphere that moves at an identical rate to the particle
What instrument is used for Particle counting ?
Electrical zone sensing (EZS) technique aka Coulter counter
For some applications, the amount of particles is important to know. Give examples of such applications
- Cell counting
- Particle contamination in injections
Name a common problem/disadvantage b/wn Sieving, Sedimentation, Microscopy and Light Scattering
These methods tell you the particle size distribution but do not tell you how many particles are present
The principle of the Hiac counter is a method used in which tests ?
Used in Pharmacopoeial tests for particles in injections
Name another method of particle counting similar to EZS (electron zone sensing)
Optical particle counting
Describe Optical particle counting
- • 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
