Pharmaceutical Powder Technology (M1) Flashcards
Mark Lecture 1 of 6
What can powder flow effect?
- Manufacturing efficiency
- Method of manufacture
- Quality of product
What factors inhibit or restrict the flow of powders?
- Adhesion (sticking to surfaces)
- Cohesion (Sticking to other like particles)
- Friction
- Interlocking factors (geometry)
- particle properties (size, shape, density, surface nature)
What factors contribute to interparticulate friction?
- rough and pitted surfaces
What is a issue that may arise from adhering or interlocking particles?
- An effect called bridging or rat-holing, in which particles being released from a funnel form a bridge or hole and so limited flow and blockages occur.
How does particle size effect resistance to flow?
Smaller particles have a higher surface area to mass ratio
greater forces of adhesion and cohesion relative to the weight and so greater resistance to flow
What is the general rule that governs particle size to flow
particles > 250um, free flowing
Particles < 100um, fairly cohesive, moderate flow
particles < 10um, extremely cohesive, unlikely to flow under gravity
What effect does density have on particle flow?
Denser particles have a greater gravitational effect acting on them so tend to flow better
What effect does water on a particle surface have on the nature of flow?
- A small amount of absorbed water vapour can reduce cohesive/adhesive forces
- Excessive moisture will likely increase attractive forces due to surface tension forces
Summarise the aspects resisting flow and the factor promoting it:
resisting (4)
- Adhesion, cohesion, friction, mechanical interlocking
promoting (4)
- Density, mass, size, nature of surface (water absorbed),
What is the angle of repose?
When a lump of powder is tipped onto a flat surface it forms a conical shaped head, the angle of this heap is the angle of repose
What does the angle of repose tell us?
It tells us the relationship balance between gravitational forces and interparticulate forces
- a high angle tells us the powder has high interparticulate forces and by extension poor flow
- Vice versa
Describe a methodology employed to identify the angle of repose
- A powder in a cylinder with a raised platform is drained
- The angle of repose of the powder remaining on the platform is calculated
What does porosity or voidage refer to when discussing powder beds?
- The % of free air or space or voids between particles
- This depends on particle shape and irregularity of the shape
What is Bulk density? and how does it differ from particle density?
Particle density is easy: it is the density of the particle
The bulk material consists of particles and voids
Bulk density is the density of the whole powder, which includes the voids, and so it is less that particle density
What do we assume when we calculate the bulk density?
- bulk Density = Mass / Vol
The mass of the voids is negligible so set to 0
s = solid, v = void
Where does this equation derive from?
- Add void ratio
What has a lower value of voidage or void:Particle ratio, Rhombohedral or Cubical Packaging?
When an aerated powder is tapped (compressed), what happens to the bulk density, the particle density and mass?
- The mass and particle density remain constant
- The bulk density increases to the tapped density
What is the Hausner Ratio?
Tapped bulk density means when the powder has been fully compressed
Do cohesive powders that form bridges and trap air have a higher or lower Hausner ratio?
What does the Hausner ratio tell us?
Cohesive powders have a high Hausner ratio >1.25, since they trap a lot of air and are therefore compressed from a larger volume.
The smaller the Hausner ratio the less the Bulk density changes when it is tapped, indicating a well flowing material
What is the compressibility index and equation?
A measure of how compressible a poured powder is:
What is Carrs index? and what does a C value below 15 mean?
A measure of powder flowability. It incorporates Hausner ratio
C < 15 means free flowing and C>25 shows poor flowability
What is the equation linking Hausner ratio to Carrs index
Explain how a tapping/jolting volumeter works
- The powder is poured into a cylinder
- The cylinder vibrates up and down compressing the powder, removing the trapped air
What can we find out from tapping a powder in a jolting volumeter
- The extent to which a powder can pack down
- How easily a powder can pack down
How can knowing/being able to predict particle size help in drug application?
From particle size we are able to predict:
- Bioavailability
- Dosage release
- Dissolution rate
- Best form of application (topical…)
Name these Particle shapes
Name 4 methods we can use to measure the cross sectional surface area of irregular shaped particle
Assume they are circular
1. Perimeter model
2. Longest Chord
3. Ferets Diameter
4. Martins
Explain the Perimeter model method for estimating particle SA
- Find the perimeter of the irregular shape
- Assume it is perfectly circular and use that as the value for perimeter to find diameter and then SA
Explain the longest chord and Ferets method for estimating particle SA
Longest Chord - Find the largest possible distance for the cross section, use this as the value for diameter
Ferets - Try and draw a line through the centre of the particle and this is the diameter then find SA from that using circular equations
What is Martins method for finding particle surface area?
- Draw a line through the centre of the particle
- Find the area of one half and then double it
How can we find the volume of a bulk powder?
What is a limitation to this method and how is it overcome?
- Using Archimedes water displacement effect
- Put the bulk powder into the water and measure the volume of water displaced
- Many powders are water soluble, so we can use an organic solvent like oil instead
How can we quantify particle shape? So look a at a ratio and know whether its a flake or needle or circular?
- Heywoods method
- Circularity ratio, true area/area from perimeter
What is sphericity?
- A measure of how spherical an object is
How do we measure sphericity? and what does a value of 0 or 1 tell us?
It is a ratio of the SA of a perfect sphere with the volume of the particle relative to the true surface area of the particle
1 - perfect sphere
0 - non-spherical like a flat flake
What 2 methods are there for measuring particle size distributions? (How much the particles vary in size?)
- Direct Methods where particle size is directly measured like Microscopy, SEM and sieving
- Indirect methods where the particle size is calculated from other measures like volume displacement, Coulter counting, gas adsorption
How does a coulter counter work?
- The particles are dissolved into a conductive solution.
- 2 sensors submerged in the solution pick up fluctuations in conductivity as particles pass between them
- This information is sent to a computer which can calculate particle size since conductivity is proportional to size
How does a surface area adsorption analyser work?
1) A known mass of powder is put into the chamber
2) The chamber is pumped full with Helium gas
3) The amount of Helium pumped in or pressure change indicates how porous the surfaces are
4) From this computers can calculate SA
Explain how we can laser deflection to identify particle size?
1) Powder is suspended in a solution to break apart the clumps (cannot be soluble)
2) A laser is directed toward the suspension which scatters the light
3) Detectors pick up the light and can recreate a profile of the particle size from the data
Explain how a nest of sieves helps divide particles by size
the powder is tipped into the top of the nest of sieves
- Finer sieves with smaller aperture are at the bottom.
- The powder falls through the column until meeting a sieve that is too fine for the particles, where they are held
What would you guess the arithmetic mean to be from this histograph data