Blending and Blend Assessment

Question 1

What is the significance of blending, and what are the effects of poor blending?

Answer 1

• produce unit doses of constant mass and volume.

- segregation or poor blending will cause issues of content uniformity.

Question 2

Describe the theory of mixing.

Answer 2

Theory of mixing talks about the different types of mixing:

1. Positive mix
   - complete and spontaneous mixing with no input of energy required (e.g miscible liquids, gases and vapors)
2. Negative mix
   - stirring is required otherwise phase separation will occur (e.g. insoluble solids in liquids, immiscible liquids)
3. Neutral mix
   - stirring is required but demixing will not occur spontaneously (e.g. mixture of powders)

Question 3

What is the ideal state of mix?

Answer 3

• particles are well distributed and in close contact with one another, alternating between one another.
• standard deviation in the composition is zero.

Question 4

What are the different mixing mechanisms?

Answer 4

1. Convective
   - Particles move from one area to another in the mixture (usually when spatula is inserted)
2. Shear
   - Slip planes are formed, unstable fractions collapse, shearing occurs.
3. Diffusive
   - Body of powder is lifted beyond its angle of repose and avalanches, resulting in the redistribution of individual particles.

Question 5

What is segregation caused by?

Answer 5

differences in particle size, shape and density

Question 6

What are the different types of segregation?

Answer 6

1. percolation segregation
2. elutriation segregation
3. projection segregation
4. feed/heap segregation
5. shear segregation

Question 7

Describe the different types of segregation.

Answer 7

1. Percolation segregation
   - finer/denser particles will filter to the bottom when powder bed is subjected to movement or vibration (e.g. vibrating bin)
2. Elutriation segregation
   - Air stream rushing through the powder bed will sift out lighter and/or finer particles ( e.g. empty tube filled with powder).
3. Projection segregation
   - When a powder mix is projected into the air, heavier particles will be projected further (e.g. under a horizontal belt conveyor).
4. Feed/heap segregation
   - Heavier/larger particles will roll further down a heap of powder (e.g. charging a hopper/bin)
5. Shear segregation
   - When 2 planes in a powder shear, the finer particles on the top layer will fill the voids of the bottom layer (e.g. powder blend flowing down the slope).

Question 8

Describe ordered mixing, and the forms that segregation may occur.

Answer 8

• process when fine particles are mixed with coarse particles and coat them to form a blend that will not segregate.
• ## termed “ordered” because constituents are not independent of one another.Segregation may occur as:
  1. ordered unit segregation
• due to size differences, larger carrier particles have more of the adsorbed component.

2. displacement segregation
   - addition of another component may compete for adsorbed component, displacing them.
3. saturation segregation
   - limited active sites on carrier particles for adsorption.
   - if saturated, additional fines will be prone to segregation by percolation.

Question 9

What is geometric dilution?

Answer 9

Process where a small amount of powder is progressively and throughly mixed with a larger entity.

Question 10

What are the different types of blending equipments?

Answer 10

Shaped bin blenders: V-cone, Y-cone, double cone

Common laboratory blender:

• drum/barrel hoop blender
• turbula mixer

Question 11

Describe the mixing process (solid-solid mixing).

Answer 11

• expansion of the beds of solids
• application of 3D shear forces to the powder bed
• allow sufficient time for the powder to reach random state
• maintain random state

Question 12

What are the factors affecting mixing?

Answer 12

• % of actives
• particle size
• particle size distribution
• particle shape

Question 13

What are the factors affecting blend homogeneity?

Answer 13

• sample size
• no. of samples
• sampling device

Question 14

What is a suitable sampling device and how does it operate?

Answer 14

• core sampler, contains 3-5 sampling points and can be sampled along the blend axis.

Question 15

What are some process variables in blending for the loading method?

Answer 15

• layer excipients one on top of the other with API in the middle.
• lubricants normally do not require layering and are thus located on the top.
• when mixing the substances, using top-bottom/radial mixing.
• end point is determined by no. of revolutions, which is affected by fill level (60% is optimum figure) for mixing.

Question 16

What are powder flow issues and how can one resolve them?

Answer 16

• powder flow issues are caused when there is no flow/powder segregation.
• Solutions:
  » external vibration: frame vibration, IBC vibration
  » internal vibration: Vibroflow

Question 17

What is a NIR device used for?

Answer 17

• PAT-enabled, used to determine homogeneity of the blend in real time.
• Homogeneity of the blend is predicted by endpoint mixing, measuring the standard deviation of the absorbance of the characteristic wavelength.
• When standard deviation approaches zero, homogeneity has been reached.

Question 18

What are the advantages of using a NIR device?

Answer 18

• no operator contact: safe for use
• real-time information
• no sampling errors