Pharmaceutical Powder Technology (M1)

Question 1

What can powder flow effect?

Answer 1

• Manufacturing efficiency
• Method of manufacture
• Quality of product

Question 2

What factors inhibit or restrict the flow of powders?

Answer 2

• Adhesion (sticking to surfaces)
• Cohesion (Sticking to other like particles)
• Friction
• Interlocking factors (geometry)
• particle properties (size, shape, density, surface nature)

Question 3

What factors contribute to interparticulate friction?

Answer 3

• rough and pitted surfaces

Question 4

What is a issue that may arise from adhering or interlocking particles?

Answer 4

• 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.

Question 5

How does particle size effect resistance to flow?

Answer 5

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

Question 6

What is the general rule that governs particle size to flow

Answer 6

particles > 250um, free flowing
Particles < 100um, fairly cohesive, moderate flow
particles < 10um, extremely cohesive, unlikely to flow under gravity

Question 7

What effect does density have on particle flow?

Answer 7

Denser particles have a greater gravitational effect acting on them so tend to flow better

Question 8

What effect does water on a particle surface have on the nature of flow?

Answer 8

• A small amount of absorbed water vapour can reduce cohesive/adhesive forces
• Excessive moisture will likely increase attractive forces due to surface tension forces

Question 9

Summarise the aspects resisting flow and the factor promoting it:

Answer 9

resisting (4)
- Adhesion, cohesion, friction, mechanical interlocking
promoting (4)
- Density, mass, size, nature of surface (water absorbed),

Question 10

What is the angle of repose?

Answer 10

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

Question 11

What does the angle of repose tell us?

Answer 11

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

Question 12

Describe a methodology employed to identify the angle of repose

Answer 12

• A powder in a cylinder with a raised platform is drained
• The angle of repose of the powder remaining on the platform is calculated

Question 13

What does porosity or voidage refer to when discussing powder beds?

Answer 13

• The % of free air or space or voids between particles
• This depends on particle shape and irregularity of the shape

Question 14

What is Bulk density? and how does it differ from particle density?

Answer 14

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

Question 15

What do we assume when we calculate the bulk density?

Answer 15

• bulk Density = Mass / Vol
  The mass of the voids is negligible so set to 0
  s = solid, v = void

Question 16

Where does this equation derive from?

Answer 16

• Add void ratio

Question 17

What has a lower value of voidage or void:Particle ratio, Rhombohedral or Cubical Packaging?

Answer 17

Question 18

When an aerated powder is tapped (compressed), what happens to the bulk density, the particle density and mass?

Answer 18

• The mass and particle density remain constant
• The bulk density increases to the tapped density

Question 19

What is the Hausner Ratio?

Answer 19

Tapped bulk density means when the powder has been fully compressed

Question 20

Do cohesive powders that form bridges and trap air have a higher or lower Hausner ratio?
What does the Hausner ratio tell us?

Answer 20

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

Question 21

What is the compressibility index and equation?

Answer 21

A measure of how compressible a poured powder is:

Question 22

What is Carrs index? and what does a C value below 15 mean?

Answer 22

A measure of powder flowability. It incorporates Hausner ratio
C < 15 means free flowing and C>25 shows poor flowability

Question 23

What is the equation linking Hausner ratio to Carrs index

Answer 23

Question 24

Explain how a tapping/jolting volumeter works

Answer 24

• The powder is poured into a cylinder
• The cylinder vibrates up and down compressing the powder, removing the trapped air

Question 25

What can we find out from tapping a powder in a jolting volumeter

Answer 25

- The extent to which a powder can pack down - How easily a powder can pack down

Question 26

How can knowing/being able to predict particle size help in drug application?

Answer 26

From particle size we are able to predict: - Bioavailability - Dosage release - Dissolution rate - Best form of application (topical...)

Question 27

Name these Particle shapes

Answer 27

Question 28

Name 4 methods we can use to measure the cross sectional surface area of irregular shaped particle

Answer 28

Assume they are circular 1. Perimeter model 2. Longest Chord 3. Ferets Diameter 4. Martins

Question 29

Explain the Perimeter model method for estimating particle SA

Answer 29

1. Find the perimeter of the irregular shape 2. Assume it is perfectly circular and use that as the value for perimeter to find diameter and then SA

Question 30

Explain the longest chord and Ferets method for estimating particle SA

Answer 30

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

Question 31

What is Martins method for finding particle surface area?

Answer 31

1. Draw a line through the centre of the particle 2. Find the area of one half and then double it

Question 32

How can we find the volume of a bulk powder? What is a limitation to this method and how is it overcome?

Answer 32

- 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

Question 33

How can we quantify particle shape? So look a at a ratio and know whether its a flake or needle or circular?

Answer 33

- Heywoods method - Circularity ratio, true area/area from perimeter

Question 34

What is sphericity?

Answer 34

- A measure of how spherical an object is

Question 35

How do we measure sphericity? and what does a value of 0 or 1 tell us?

Answer 35

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

Question 36

What 2 methods are there for measuring particle size distributions? (How much the particles vary in size?)

Answer 36

- 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

Question 37

How does a coulter counter work?

Answer 37

- 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

Question 38

How does a surface area adsorption analyser work?

Answer 38

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

Question 39

Explain how we can laser deflection to identify particle size?

Answer 39

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

Question 40

Explain how a nest of sieves helps divide particles by size

Answer 40

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

Question 41

What would you guess the arithmetic mean to be from this histograph data

Answer 41