Victor lectures - particle size

• appearance of mediated powders

• flow properties of granules for tableting

• stability in emulsion and suspensions

• efficacy of drug delivery

• texture and feel of semi-solids

how particle size influences manufacturing

• diluent/binder

• sufficent hardness

• good disintegration properties

lactose

• uneven particle flow - excessive air trapment - causing capping of tablets

• Smaller powder particles stick together much more easily than larger ones as they clump together, the powder cannot pour or flow smoothly.

• larger than 250 microns - free flowing

• below 10 microns - aggregate

particle size influences manufacturing

• using larger particles as they will be less likely to aggregate or clump to each other

• thus why granules are used instead of fine powders

• increasing the number of larger particles and removing the small particles creating a better distribution

how to alter the particle size and its distrubution

• Perfectly round spheres are easy to measure with just one number (diameter).

• real drug powders look like jagged, random rocks under a microscope, you cannot accurately describe their true size using only one simple measurement

• the measurements are compared with previous supplies for quality assurance

measuring of 3D particles

• can't easily measure a jagged particle's exact uneven shape, we pretend it's a perfect sphere.

• then find a single diameter measurement that matches one specific property of our real particle.

• hypothetical of the true size and shape

Equivalent square theory

• The volume of an irregular particle is equal to the volume of a hypothetical spherical particle

volume-equivalent square theory

• The surface area of an irregular particle is equal to the surface area of a hypothetical spherical particle

surface area-equivalent square

• volume, surface area, weight, are all different properties of the particle and cant be compared against each other

each equivalent-square measurement

• depends on which property you are interested in e.g. volume, surface area

• e.g. aerosol for lungs - measure aerodynamic diameter

when to use the equivalent square measurement

• dried powders or powders in a liquid suspension

• wet and dry sieving

Sieving

• sieve diameter - minimum width that can pass through the sieve aperture

• powder is added to the coarsest end of the sieve, mechanical agitation is used to allowing the particles with the smallest width to be able to pass through the minimum sieve aperture

• the weight is collected and used to plot a cumulative undersize plot

Sieving proccess

• 40 to 125 microns

• measurement range depends on density, agglomerate, and electrostatic charge

Dry sieving

• measurement range - 20 microns

• air jet sieving is an alternative - can be used for 10 microns

Wet sieving

• projected area diameter

• perimeter diameter

• Feret diameter

• Martin diameter

• using light microscopy to produce 2D images of 3D particles

Manual image analysis

• high resolution technique

• 1 micron to millimeters

• individual particle sizes are captured based on size, shape, physical properties but represent the whole sample

• use together with other methods such as laser diffraction

Automated imaging

• stationery dispersed samples

• sample flows and captures images

• 0.5 to 1300 microns

Static automatic imaging

• stream of particles generated and recorded

• allows to see the motion of the particles

• movement by pouring or through liquid or air steam

• 20 to 30 microns

Dynamic automatic imaging

• shining the laser through the particles

• larger particles scatter the light at smaller angles compared to the smaller particles

• the angular scattering density is analysed and used to calculate the size of the particles that create the scattering pattern and represented as volume diameter

• particles must be dispersed

• can be in a liquid and requires mechanical agitation

• dry powders use a compressed gas at a pressure for dispersion

• particle size is reported as a volume equivalent sphere diameter

Laser diffraction

• shows data for particle size distribution and mean particle size

• Electrophoretic Light Scattering (ELS)

• Static Light Scattering (SLS) - measures electrical charge (zeta potential) and molecular mass

• measures - Hydrodynamic diameter, dh, refers to how a particle diffuses within a fluid.

• particle has the same translational diffusion coefficient as hypothetical sphere

• particles are suspended in a liquid and mechanical agitation occurs to disperse the particles

• undergo Brownian motion - collisions between suspended particles and solvent which is heat induced

• small particles scatter the light more than larger particles

Dynamic Light scattering

• accumulation of particles with differing range of size

• based on mean, median, mode

• can be bimodal or trimodal

• histogram or frequency diagram is used

• can be accumulative histogram or with individual fractions

distrubution

• increases

• difference in weight before and after sieving is measured

weight after sieveing

• range of distribution of the particles

• D10 - 10% of all particles in your sample are smaller than certain number

• D50 - 50% of all particles in your sample are small than certain number

• D90 - 90% of all particles in your sample are smaller than certain number

distribution width

• Dynamic - uses particles in a solution and are moving and uses brownian motion, where the small particles move more flickering the light while - smaller microns are tested compared to laser

• Laser uses static particles which are light is shine through on them

• Laser - is able to scatter the light

Compare and contrast laser diffraction method and dynamic light scattering method