Particle size analysis 1 and Particle Size analysis 2 Flashcards
Why do you need to determine particle size?
- To determine properties of many pharmaceutical formulations
- To study the factors influencing stability, bioavaliability and pharmacological effects of many formulations to assist in designing of dosafe forms/formulations
- To understand behaviour of many pharmaceutical dispersions
- QC of pharmaceutical formulations (emulsion, suspension, injectable solutions)
- Evaluation formulation and its admixture stability
Discuss particle size and distribution
>For asymmetrical particles, particle size is equivalent to spherical diameter
- surface diameter (ds): the diameter of a sphere having the same surface area
- volume diameter (dv): diameter of a sphere having the same volume
- Volume surface diameter (dvs): the diameter of a sphere having the same external surface area to volume ratio or surface area per unit volume as the particle.
- Stoke diameter ( dst) : the diameter of an equivalent sphere undergoing sedimentation at the same rate as the particle of interest.
What is mean and median particle size and how is it calculated
- Calculated from a population/batch of particles and is used as basis for comparison.
- Particle size of the same batch material can vary depending on the method of determination
- Mean diameter (dave): ie average diameter. Size distribution is complete with known upper & lower size.
- Median diameter: equivalent to geometric mean diameter, dg. A diameter at 50% cumulative frequency. Incomplete particle size distribution.
What do particles of undersize or oversize mean?
Particles of undersize or oversize refer to all particles either below certain size or above certain size which get measured.
- If particles of undersize are analysed then the 100% frequency should be with the maximum size of the particles.
Regarding the methods for particle size analysis –> What is the method of choice based on?
- Measuring size range required (minimum & maximum size of particle)
- Precision required
- Quantity of sample to be analysed & sample measurement environment ( wet or dry)
- Whether particle shape/image is important
What is microscopy? (1st method of particle size analysis)
Microscopy (optical and electron) pratical size range:
optical –> 1-1000 micron (mostly 0.2-100 micron)
electron < 1000 micron
- Need to measure 300-500 particles
- Time consuming
- Can use computer software for sizing
- A good alternative method
- Can provide information on particle agglomeration, shape and number of types/component + surface characteristics of particles
What is electrical sensing zone (coulter counter)? (2nd method of particle size analysis)
- It measures particle volume (undersize)
- Particle samples suspended in a solution containing electrolytes, passing through a small orifice on either side of which are electrodes, generates a change in the electric signal.
- Such a change is proportional to the volume of the particle as the particle displace its own volume of electrolyte and therefore produces a electric resistance or pulse which is related to the particle volume.
- The technique is used both to count particles to determine particle concentration in a solution and to study particle size distribution.
- Particle diameter measurement range is 0.1 micron to 1000 micron
What is sieving? (3rd method of particle size analysis)
- Using a series of standard sieves
- Used for coarse particles or powders
- The powder is shaken for a controlled time
- Then the powder retained on each sieve is collected and weighted
- Size range : 5 micron – 125 mm
- Measures particles of undersize
- Needs a large volume of samples
- Variables affecting the measurements: sieve load Duration and intensity of shaking Attrition/grinding down of granular materials
- Caution to be taken to control the sieving condition
What is sedimentation(stokes law)? (4th method of particle size analysis)
Stokes law = V = H/T
V= Rate of settling H= distance of fall in time T=time
Stokes law is appplicable to:
- Spherical particles
- Irregular particles with the size equivalent to that of sphere falling at the same speed
Sedimentation:
- Particles must be free of aggregates
- Proper deflocculating agent must be used so particles can be kept free and separate as they fall (deflocculating = to not cause clumps)
- Combination of ultracentrifugation sedimentation and x ray –> sedimentation normally can measure particles from 0.5-1000 micron
What is light obscuration/blockage (HIAC/Royco)? (5th method of particle size analysis)
- Use laser as light beam or laser diode as detector
- Particles passing through will interrupt the light beam and reduce the amount of light that reaches the detector. This decrease in light transmission is proportional to the projected areas of the particles
- Use for detecting particle contamination of injectables
- Use for measuring particle size and size distribution
- Size range 1-400 micron ( machine dependent)
- Multiple channels
- Measure particles of oversize
What is Laser light scattering method (laser diffraction)? (6th method of particle size analysis)
A technique for measuring the size (volume diameter dv) of particles ( wet or dry) in the region 0.02-2000 micron eg Malvern Mastersizer 2000
- Instruments are based on interaction of laser light with a particle
- Particles passsing through a laser beam will scatter light at an angle that is directly related to their size
>Small particle size = larger scattering angle
>Scattering intensity dependent on particle size, diminishing with small aprticle volume
- Therefore, small particles scatter at wider angles but with low intensity (light intensity produced in proportion to particle diameter)
- Particle size distributions are calculated by comparing a sample’s scattering pattern with an appropriate optical model
Fraunhofer approximation and mie theory
Fraunhofer approximation asumes that particles beaing measured are opaque and scatter light at narrow angles –> only applicable to large particles
Mie Theory provides calculation of particle size distributions for all particles
- It allows for primary scattering from the surface of the particle
- Also predict the secondary scattering caused by light refraction within the particle
Advantages of LLS
- Flexibility
- Wide size range –> rapid
- Reproductibility, but may require a large sample size, depending on the machine
Dynamic Light Scattering (DLS)/ Photon Correlation Spectroscopy(PCS) (7th method for particle size analysis)
- A technique for measuring the size (hydrodynamic diameter ) of particles in the sub-micron region when they are suspending in a liquid , eg Malvern Zetasizer
- DLS measures Brownian motion (via the analysis of the intensity of fluctuations of scattered light) and relates this to the size of the particles.
- The larger the particle, the slower the Brownian motion will be. Smaller particles are “kicked” further by the solvent molecules and move more rapidly.
What Dynamic Light Scattering (equation and graphs)
- Measures the time dependent fluctuations in the scattering intensity to determine translational diffusion coefficient (D) and subsequently the hydrodynamic diameter (DH) –> (from stokes-einstein equation)
What is the particle size range?
Particle size range: 1nm - 1micron
laser: closer to the wavelenth of the light
model: mia theory
- Intensity data produce mean size (z-avg diameter)
- Estimate of the width of the distribution (polydispersity index, PDI)
What is surface area and its determination (8th method for particle size analysis)
Gas adsorption method
- BELSOR- mini II is a compact volumetric adsoprtion measurement instrument used for specific area and pore distribution
- Measurement; measures 3 samples simultaneously
Air permeability methods
- TONIPERM Microprocess controlled air permeability tester for determination of the specific surface of powders
