Powders

Question 1

Does powder acts a liquid?

Answer 1

In some ways powder does act as a liquid (it can be poured) however the flow is not completely free. If your poured powder it would create a mound which it wouldn’t with water.

Question 2

What are the key concepts to consider when manufacturing tablets and capsules?

Answer 2

The manufacture depends on the relevant flow properties of the solid. These flow properties include the particle size, shape, interactions with other particles and how well the drug particles interact with excipients.

Question 3

Which factor influences drug dissolution rate?

Answer 3

The Noyes-Whitney equation:

dm/dt = DA (Cs-C) / h

By the equation surface area has the greatest impact on drug dissolution rate; the greater the surface area, the greater the rate of drug dissolution.

Question 4

Why is the size of the particle not always an important factor to consider?

Answer 4

For a drug to be absorbed across the GI tract it can either be absorption or dissolution rate limited. Dissolution rate is influenced by particle size/shape but absorption is influenced by solubility of a drug so if a drug is absorption rate limited then particle size is irrelevant.

Question 5

What is the structure of a powder particle?

Answer 5

Powders are of crystalline structure and each particle is composed of multiple crystals bonded together.

Question 6

When is a powder particle distinct and when is it a collection of smaller particles?

Answer 6

When a powder is poured not every powder particle falls by itself using aggregates fall together (clump of particles). When the intermolecular attractions between the particles are stronger than the force of gravity acting on a single particle this is a collection of small particles.

Question 7

Define monosized and mono dispersed?

Answer 7

Mono sized- the average particle size is equal

Mono dispersed- equal distribution of the particles

Question 8

Describe a method of data collection for measuring particle size.

Answer 8

Essentially set up a sieve tower with the widest mesh at the top and finest at the bottom. The sieve is shaken for approximately 20 minutes. From this you can weigh the mass of the particles at each sieve level.

Question 9

Describe methods of data representation of particle size.

Answer 9

Firstly a histogram plotting particle size against frequency.
A line graph cumulative weight of undersized particle against particle size which can be compared to a line graph of the cumulative weight of oversized particles against particle size.

Question 10

What are some of the values you could interpret from a cumulative weight graph?

Answer 10

Median (middle value)

Lower quartile (max total weight x 0.25)

Upper quartile (max value x 0.75)

Interquartile range (upper-lower quartile)

Question 11

What is air jet sieving?

Answer 11

A partial vacuum is applied to a sieve tower and the particles are pulled through.
More accurate than the manually shaken sieve tower as it ensures that the particles are in their corresponding column regardless of time.

Question 12

What are the four measuring systems of particle diameters?

Answer 12

Projected perimeter diameter- circle drawn around particle touching the edges of it.
Projected area diameter- circle is drawn around the particle with the extra outside equal to gaps inside.
Martin’s diameter- line is drawn through the particle where the area on each side is equal.
Feret’s diameter- measuring the chord length of many different particles on one orientation.

Question 13

Describe the concept of Electrical Stream sensing zone method.

Answer 13

Particles are firstly suspended in an electrolyte solution. The particles then pass through an aperture (hole/opening) between the two electrodes. When this happens the disturbance in the electric field is proportional to the volume of the particle.

Question 14

What are the advantages/disadvantages of using the ESSZ method?

Answer 14

Advantages:
Quick and easy to use (automated)
Can measure within the range of 0.1-1000 micrometers

Disadvantages:
Solution may have to be saturated first in an aqueous solvent to prevent dissolution.
Assumes that every particle that passes through is an individual particle.

Question 15

What can be concluded from the laser light scattering method?

Answer 15

The greater the diffraction that has occurred, the smaller the particle.

Question 16

Why is flow of powder essential?

Answer 16

When bulk manufacturing occurs, you want an equal distribution of active ingredient and excipients in each of the tablets.

Question 17

What are the two attractions that affect the flow of powder?

Answer 17

Adhesion- this is the attraction between two different materials
Cohesion- the attraction between two identical materials.

A powder with stronger cohesive attraction will not flow effectively

Question 18

What are the interparticulate forces in a powder?

Answer 18

Firstly there are van der waals forces between each powder particle. Finer particle will be more cohesive.

There are also surface tension forces (each particle due to the atmosphere we live in will have a a few water molecules on the surface).

Electrostatic charging (static shock)

Question 19

What forces impact whether a powder particle moves or not?

Answer 19

Essentially when power is poured and an upside down cone shape is formed, powder particles will either continue to fall down the sides or stick.
The two forces acting on the powder particle are the cohesive attraction with other powder particles and the force of gravity (F = mg).
When mg is greater than the cohesive attraction, the particle moves.
When the cohesive attraction is greater than mg, the particle sticks.
This is why finer particles are more likely to stick as the force of attraction is reduced (mass is reduced) so it is more likely that the cohesive attraction forces will outweigh mg.

Question 20

What data can be collected from powder flow to suggest the cohesiveness of a powder?

Answer 20

Pour a powder and it should form a pile (normally shaped like an upside down cone).
Measure the angle of repose which is the angle of the slant of the cone to the horizontal.

Question 21

What range of values are considered to suggest high cohesion?

Answer 21

Angles of above 50 degrees, high cohesion/poor flow
25-50 degrees okay flow
Around 25, low cohesion/ good flow

Question 22

What does the Hausner ratio tell us and how can it be calculated?

Answer 22

The Hausner ratio is a measure of flowability and can is calculated by the equation:

Hausner ratio: Df/D0

Df: final bulk density after tapping
D0: initial (fluffy) density

To record values essentially a material is put into a machine and mechanically ‘tapped’ for a period of time.

As density is equal to mass/volume and the mass remains constant it can be rearranged to:

Hausner ratio: V0/Vf

Question 23

How does volume/density before and after tapping relate to cohesion?

Answer 23

Cohesive material form arches and bridges due to interparticulate attractions which collapses on tapping. So the Hausner ratio (density) would be quite low if there was good flow (about 1.2) and higher than 1.6 is poor flow (considerably cohesive).

Question 24

How do flow rates differ through a hopper?

Answer 24

At the beginning particles which are vertically above the opening flow through.
An expanding central channel then forms as particles continue to flow until dead zones form (particles get stuck to the sides).
The angle of the slope of the dead zones is equal to the angle of repose.

Question 25

How can a design be modified to ensure dead zones do not form?

Answer 25

At the end of a tube it becomes a funnel shape. The wall angles ensure dead zones can’t form. These wall angles can’t be too small otherwise it will flow straight through. If they are too large then the flow rate will not be reproducible.

Question 26

Explain the concept of rat holing?

Answer 26

This occurs in powder flow using a funnel shaped beaker with one than one material. It is essentially when flow only occurs in the central channel and the cohesive materials are position either side.
Sometimes the rat hole can collapse and then there would be a dramatic increase in concentration of the cohesive material.

Question 27

What kind of flow would you want to have an even distribution of active ingredient within a drug?

Answer 27

Ideally you would want mass flow, this is where the discharge from everywhere in the Hopper design funnel flows at the same rate. Here the first particle in, would be the first particle out. This is a reproducible flow method for ensuring equal concentrations of active ingredients and excipients within all manufactured tablets/capsules.

Question 28

How is random mixing defined?

Answer 28

Random mixing- the probability of finding a ‘blue’ molecule is equal to the total number of ‘blue’ molecules within the mixture.

Question 29

How can you measure the extent of randomness?

Answer 29

Essentially take lots of different samples. Sample size should be picked carefully. The larger the sample is, it gives an impression of less variation. Might be useful to take samples firstly at a lower scale and then two more at upper scales.

Question 30

Are larger or smaller particles more likely to give an even distribution?

Answer 30

Smaller particles

Question 31

What are the three mechanisms of mixing?

Answer 31

Convection mixing: displacing one portion of substance (mechanically moving it).

Shear mixing: powder heap collapses into a hole created.

Diffusive mixing: powder bed is picked up and then dropped again.

Question 32

What types of mixing occurs in agitator and tumbling mixers?

Answer 32

Agitator mixers- Shear and Convection

Tumbling mixers- Shear and diffusive

Question 33

What happens if powder is mixed for too long?

Answer 33

Eventually the mixture becomes segregated and this often occurs if there is differences in particle size, shape and density and if the powder is vibrated and have good flow properties.

Question 34

Explain the concept of percolation segregation.

Answer 34

This is the segregation caused by differences in particle sizes. If a system is vibrated larger particles will experience a great force of attraction due to gravity, they will accelerate quicker downwards. Essentially separate layers of particles within the powder will form.

Question 35

Explain the concept of trajectory segregation.

Answer 35

This is powder segregation due to differences in densities. On mixing kinetic energy is transferred to the particle powders. Larger particles have greater momentum (p = mv) and so they will move greater distances.