Particle Size Analysis

Question 1

Importance of particle size

Answer 1

• It affects physicochemical and pharmacological properties e.g. via dissolution rate (higher the dissolution rate, faster the onset of action)
  
  • It affects processing properties of powders e.g. flowability, mixing (good flow and mixing properties make manufacture process easier)
    It affects formulation performance e.g. stability of dispersed systems (better stability, longer shelf life)

Question 2

Classes of powders (5)

Answer 2

1. Coarse
2. Moderately fine powder
3. Fine powder.
4. Very fine powder
5. Micronized powder

Question 3

Coarse powder

Answer 3

> 355

Question 4

Moderately fine powder

Answer 4

180-355

Question 5

Fine powder

Answer 5

125-180

Question 6

Very fine powder

Answer 6

<125

Question 7

Micronized powder

Answer 7

<10

Question 8

Large geometric objects

Answer 8

Size is described in three dimensions

Question 9

Small, ireegular particles

Answer 9

3D size description is impractical, only one dimension (average diameter) is used

Question 10

Martin’s diameter

Answer 10

The length of the line which bisects the image of particle

Question 11

Feret’s diameter (dF)

Answer 11

The distance between two tangents on opposite sides of the particle, parallel to some fixed direction
Feret’s and Martin’s diameters are taken from a statistical mean of diameters measured from different particle orientations

Question 12

Examples of choosing the right diameter

Answer 12

Suspension: sedimentation properties - Stokes’ diameter
Inhaled particles: aerosol deposition in the lungs - aerodynamic diameter

Question 13

Histogram VS cumulative distribution

Answer 13

Histogram is termed an incremental distribution because it shows how many particles fall within a given size increment
A cumulative distribution shows how much material lies above or below a particular size

Question 14

What do both histograms and cumulative differences show?

Answer 14

• Reflects the distribution of particle sizes
• Presents an interpretation of the particle size distribution
• Enables determination of the percentage of particles having equivalent diameters
• Allows different particle size distributions to be compared

Question 15

What is skewness

Answer 15

A measure of the asymmetry of distribution, can be negative or positive

Question 16

Different distribbution shapes

Answer 16

Distributions may have a pointed or rounded shape, this is quantified as the kurtosis of the distribution
Pointed - leptokurtic
Flattened - platykurtic

Question 17

Cumulative size distribution

Answer 17

look at slide

Question 18

Do I need to know which & of the powder falls into a specific size increment? Do I want quick information on the particle size distribution

Answer 18

Incremental

Question 19

Do I need to know which % of the powder is smaller or larger than a specific size

Answer 19

Cumulative

Question 20

Histograms measure

Answer 20

Central tedency
Dispesion

Question 21

What is central tendency

Answer 21

The tendency of the particle size to cluster around a particular value.
Such values are evident as a peak in the particle size distribution
These values are normally known as ‘averages’ or ‘means’ of set of data
3 diff quantities: mode, median and mean

Question 22

Mode

Answer 22

Peak value of the distribution
If the distribution has 2 or more peaks it is bimodal or multimodal

Question 23

Median

Answer 23

D50 value is the size which splits the distribution into 2 halves with 50% of the mass or particle number larger and 50% smaller
To find D50 construct a cumulative graph, from which the 50% can be read off directly

Question 24

Monodisperse

Answer 24

If the particles in a sample are all of the same size

Question 25

Polydisperse

Answer 25

If a range of particle sizes exists

Question 26

PSA (6)

Answer 26

1. Sieve analysis 2. Microscopy 3. Sedimentation 4. Coulter counter (electrical sensing zone) 5. Laser diffraction 6. Dynamic light scattering (photon correlation spectroscopy)

Question 27

Criteria for choosing a method of PSA

Answer 27

What particle properties are the most important? What size particles will be measured? How is the sample prepared: wet or dry? Speed of analysis Availability Cost

Question 28

Sieve equivalent diameter

Answer 28

Minimum square aperture through which the particle will pass. it is a 2D value Sieving is rarely complete as some particles take long time to orientate themselves over the sieve apertures to pass through Recommended sieving be continued until <0.2% of material passes a given aperture in any 5-minute interval

Question 29

Sieve analysis

Answer 29

Size range: 5 micro > 5000 micrmoetres; intended for use where at least 80% of particles are larger than 75 micrometres Sieve shaker: stack of sieves of various sieve size, 6-8 sieves in order of root 2 progression, largest on top Type of diameter: equivalent size diameter Dry or wet sieving Sample size 0.5 to few kg Measuremtn time: 5-30 min for dry sieving

Question 30

Advantages and disadvantage of sieve analysis

Answer 30

Pros: inexpensive, easy to perform well-established Cons: time consuming, problems of reproducibility, humidity, static electricity and powder cohesivity can affect the results, particles may break or agglomerate during sieving, 2D measurement

Question 31

Microscopy

Answer 31

Light - 1-1000 micrometres Electron - 0.1-1000 (staining/coating is required) Sieve analysis is preferred for >200

Question 32

How does analysis via microscopy work?

Answer 32

Usually projected area diameter, also Feret's or Martin's diameter Single particles and aggregates can be distinguished 600 or more particles to be measured Distribution by number Use computer-based image analysis for calculation of size distributions

Question 33

Advantages and disadvantages of analysis by microscopy

Answer 33

Pros: cheap light microscope, small sample size, individual particles sized, images can be captured Cons: expensive electron microscope, time consuming, low throughput, 2D measurement, operator dependent

Question 34

What is Stokes' diameter

Answer 34

Particles with different size settle at different velocities Based on the application of Stokes' Law - determination of the sedimentation velocity by measuring the time which particles require to settle Size range: 5-200 micrometres Distribution. by weight Sample: dispersion of dry powder, suspensions, emulsions Sample size: micrograms to mg quantities

Question 35

Advantages and disadvantages of analysis by sedimentations

Answer 35

Pros: low cost, useful for cases where sedimentation is key Cons: labour intensive, particles must be inosliuble in the dispersion medium, temperature control is required, particle shape affects its settling rate

Question 36

How does coulter counter work

Answer 36

* Measurement by conducitivity, a type of electrical sensing zone method * As particles pass through the aperture opening, they bend the current flux lines around the particles * This causes a longer length for the current to pass and a higher resistance to the current * The amplitude of this current pulse is directly proportional to the volume of the particle that produced it = Volume diameter (dV)

Question 37

Quick info about coulter counter size range / distribution / sample / sample size

Answer 37

Volume equivalent diameter Size range: 0.5-1000 micrometres Distribution by number Sample: Particle suspension in conductive liquid Sample size: mg to gram quantities depending on particle size

Question 38

Advantages and disadvantages of coulter counter

Answer 38

Pros: rapid measurement, large number of particles counter-reproducible and reliable, simple to use, wide range of sizes measured Cons: particles have to be suspended in an electrolyte liquid, limited choice of liquid media, blockage of orifice by oversized particles, needs calibration, expensive

Question 39

Laser diffraction how does it work

Answer 39

Technique based on laser diffraction derive particle size information from patterns of light scattering of the sample

Question 40

Quick info about laser diffraction size range / distribution / sample / sample size

Answer 40

Equivalent volume diameter Size range: 0.01 to 3000 micrometres Diffraction occurs at the surface of a particle if its refractive index is different from the dispersant Larger particles - scatter light at a smaller angles with higher intensity, and vice versa The angular scattering intensity data is analysed to calculate the size of the particles Distribution by volume Sample size: mg-> g quantities

Question 41

Advantages and disadvantages of laser diffraction

Answer 41

Pros: quick and simple, no calibration required, high reproducibility, testing is no destructive and non intrusive, entire sample is measured, suitable for a wide range of samples Cons: refractive index should be known, refractive index difference required between particles and dispersion medium, expensive

Question 42

Dynamic light scattering - how does it work?

Answer 42

Photon correlation spectroscopy (PCS) * Primarily used to measure nanoparticulate colloid systems such as liposomes, nanoparticles and micelles * The fluctuations in the intensity of the scattered light are due to the random Brownian motion of particles suspended in a suspending medium * The rate of Brownian motion depends on particle size

Question 43

DLS quick info

Answer 43

Hydrodynamic diameter - using Stokes-Einstein equation Size range: 1 nm to 3 micrometres Distribution by intensite Sample: suspension, emulsion Sample size: micrograms to mg quantities

Question 44

Pros and cons of DLS

Answer 44

Pros: quick and simple, no calibration, high reproducibility, non destrustive and non intursive, entire sample is measured, nanoparticle size range Cons: samples must be dispersed in liquid, particle-particle interaction at increased conc, multiple scattering at increased concentration, expensive

Question 45

Summary of sizing method

Answer 45

Look at table at end of lecture notes

Question 46

Able to...

Answer 46

Appreciate importance of particle size Define equivalent diameters and particle size distribution Discuss the use and appropriateness of particle sizing methods