Particle Size Analysis Flashcards
Appreciate the importance of particle size Define equivalent diameters and particle size distribution Discuss the use and appropriateness of particle sizing methods
Importance of particle size
- 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)
- It affects processing properties of powders e.g. flowability, mixing (good flow and mixing properties make manufacture process easier)
Classes of powders (5)
- Coarse
- Moderately fine powder
- Fine powder.
- Very fine powder
- Micronized powder
Coarse powder
> 355
Moderately fine powder
180-355
Fine powder
125-180
Very fine powder
<125
Micronized powder
<10
Large geometric objects
Size is described in three dimensions
Small, ireegular particles
3D size description is impractical, only one dimension (average diameter) is used
Martin’s diameter
The length of the line which bisects the image of particle
Feret’s diameter (dF)
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
Examples of choosing the right diameter
Suspension: sedimentation properties - Stokes’ diameter
Inhaled particles: aerosol deposition in the lungs - aerodynamic diameter
Histogram VS cumulative distribution
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
What do both histograms and cumulative differences show?
- 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
What is skewness
A measure of the asymmetry of distribution, can be negative or positive
Different distribbution shapes
Distributions may have a pointed or rounded shape, this is quantified as the kurtosis of the distribution
Pointed - leptokurtic
Flattened - platykurtic
Cumulative size distribution
look at slide
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
Incremental
Do I need to know which % of the powder is smaller or larger than a specific size
Cumulative
Histograms measure
Central tedency
Dispesion
What is central tendency
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
Mode
Peak value of the distribution
If the distribution has 2 or more peaks it is bimodal or multimodal
Median
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
Monodisperse
If the particles in a sample are all of the same size
Polydisperse
If a range of particle sizes exists
PSA (6)
- Sieve analysis
- Microscopy
- Sedimentation
- Coulter counter (electrical sensing zone)
- Laser diffraction
- Dynamic light scattering (photon correlation spectroscopy)
Criteria for choosing a method of PSA
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
Sieve equivalent diameter
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
Sieve analysis
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
Advantages and disadvantage of sieve analysis
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
Microscopy
Light - 1-1000 micrometres
Electron - 0.1-1000 (staining/coating is required)
Sieve analysis is preferred for >200
How does analysis via microscopy work?
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
Advantages and disadvantages of analysis by microscopy
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
What is Stokes’ diameter
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
Advantages and disadvantages of analysis by sedimentations
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
How does coulter counter work
- 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)
Quick info about coulter counter size range / distribution / sample / sample size
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
Advantages and disadvantages of coulter counter
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
Laser diffraction how does it work
Technique based on laser diffraction derive particle size information from patterns of light scattering of the sample
Quick info about laser diffraction size range / distribution / sample / sample size
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
Advantages and disadvantages of laser diffraction
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
Dynamic light scattering - how does it work?
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
DLS quick info
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
Pros and cons of DLS
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
Summary of sizing method
Look at table at end of lecture notes
Able to…
Appreciate importance of particle size
Define equivalent diameters and particle size distribution
Discuss the use and appropriateness of particle sizing methods
