Blending and Blend Assessment Flashcards

1
Q

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

A
  • produce unit doses of constant mass and volume.

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

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2
Q

Describe the theory of mixing.

A

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)
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3
Q

What is the ideal state of mix?

A
  • particles are well distributed and in close contact with one another, alternating between one another.
  • standard deviation in the composition is zero.
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4
Q

What are the different mixing mechanisms?

A
  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.
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5
Q

What is segregation caused by?

A

differences in particle size, shape and density

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6
Q

What are the different types of segregation?

A
  1. percolation segregation
  2. elutriation segregation
  3. projection segregation
  4. feed/heap segregation
  5. shear segregation
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7
Q

Describe the different types of segregation.

A
  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).
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8
Q

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

A
  • 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.
  1. displacement segregation
    - addition of another component may compete for adsorbed component, displacing them.
  2. saturation segregation
    - limited active sites on carrier particles for adsorption.
    - if saturated, additional fines will be prone to segregation by percolation.
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9
Q

What is geometric dilution?

A

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

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10
Q

What are the different types of blending equipments?

A

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

Common laboratory blender:

  • drum/barrel hoop blender
  • turbula mixer
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11
Q

Describe the mixing process (solid-solid mixing).

A
  • 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
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12
Q

What are the factors affecting mixing?

A
  • % of actives
  • particle size
  • particle size distribution
  • particle shape
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13
Q

What are the factors affecting blend homogeneity?

A
  • sample size
  • no. of samples
  • sampling device
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14
Q

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

A
  • core sampler, contains 3-5 sampling points and can be sampled along the blend axis.
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15
Q

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

A
  • 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.
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16
Q

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

A
  • powder flow issues are caused when there is no flow/powder segregation.
  • Solutions:
    » external vibration: frame vibration, IBC vibration
    » internal vibration: Vibroflow
17
Q

What is a NIR device used for?

A
  • 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.
18
Q

What are the advantages of using a NIR device?

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