Particle Size Analysis Flashcards
Particle size analysis
Particle characterisation, particle counting and examination of particle size distributions
Particle size analysis methods
Wide range of techniques
Wide range of instruments for some techniques
Each technique/instrument will present data/results in a different way
Harmonisation of validation methods for each technique arising from standardisation committees
New techniques continually being introduced
Methods available
Visual inspection Microscopy- visual, electron Electrical sensing zone Light blockage Light scattering- laser diffraction, PCS Sieving Sedimentation- gravity, centrifugal or field flow fractionation Impactors Ultrasonics
Why do we use particle size analysis?
Bioavailability- size affects dissolution rate
Production/manufacture- flow properties affected by size, also mixing of powders
Suspension and emulsions- sedimentation or creaming, stability on dilution
Inhalation- aerosols deposition
Parenteral products- physiological hazard, cosmetic acceptability
Topicals- cosmetic acceptability
Production- clean rooms
Surface area and particle size
Increased drug surface area produces increased dissolution rate
Decreasing drug particle size increases surface area
Reducing particle size may produce wetting problems especially for hydrophobic drugs- add a wetting agent to increase effective surface area
Important particle size analysis factors
Knowledge of sample materials properties
Sampling
Expected results and data presentation
Knowledge of particle size analysis techniques- choice of appropriate method
Handling of sample material and its carrier vehicle e.g. cleanliness
Sampling
Comparison of process material(100kg) vs gross sample(kg) vs lab sample(g) vs measurement sample(mg)
Want a perfect representative sample
Will always have variation- sampler bias, operator bias, time point
Bulk sampling
Powders unmix when poured into a heap
Finer particles tend to remain in the centre
Visual inspection
Most important method
Improve observation conditions- use black and white backgrounds, use good lighting, use light projected through sample at different angles, use fibre optic lighting
If particles can be seen with the naked eye, chances are that other techniques will give false results
Problems: operator variability, validation
Visual classification systems
Homogenous- uniform appearance throughout- acceptable
Slight creaming- cream layer <5micrometres, easily re-dispersed- acceptable
Heavy reaming- cream layer >5micrometres with occasional aqueous layer at base, re-dispersion possible- acceptable
Flocculated- not re-dispersible- unacceptable
Cracked- free oil present- unacceptable
Optical/light microscopy
The only technique in which the particles are observed
Normally cheap and with rapid methods of preparation
Quality of microscope important- calibration
Sampling: representiveness of the sample must be assured
Problem- contamination e.g. air or other components
Operator error, need to count large numbers for statistical purposes
Automation- image analysis
Electrical sensing zone
Measurement of change in electrical resistance across a glass aperture orifice, when the sample particles (suspended in an electrically conducting media) are drawn through the orifice
Resistance change proportional to size of particle
Different apertures cover different size ranges
Orifice can get blocked
Light blockage
Measure of obscured white light or laser projected beam
BP recommended method for QC assessment of particulates in injectable products
Also referred to as light obscuration counting
Particle counter- one micrometre or greater
Problems with carrier fluid optical properties
Sample preparation important
Limited sample data bins
Laser light scattering methods
Scattering methods- 1nm to 10 micrometres
Diffraction methods- 100nm to 1000 micrometres +
Rapid and accessible methods
Sample preparation- suspension in liquid or air- aerosol
Need a media in which the particle in insoluble, may need dispersing agent
Problems with sedimentation rate (stirring)
Laser light scattering methods- PCS
Side scatter- Photon Correlation Spectroscopy (PCS)- also known as quasielectric light scattering (QELS)
Small particles- rapid and weak scatter at wide angles
Large particles- slow and strong scatter
Brownian motion- dependence on viscosity and temperature- particle shape effects minimised
