Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Solids > Blending > Flashcards

Blending Flashcards

1
Q

Theory of mixing

A

1) Positive mix
- Complete & spontaneous mixing due to diffusion
- E.g. Miscible liquids

2) Negative mix
- Phases will separate unless work is carried out
- E.g. Suspensions (will sediment), immiscible liquids (e.g. oil & water)

3) Neutral mix
- Work required to mix
- Will NOT demix spontaneously
- E.g. Mixture of powders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Evaluation of mix

A

Mixed powders will always exhibit some variation in composition of powder

Target: Random mix
- Low standard deviation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Mixing mechanism

A

1) Convective
- Movement of a group of adjacent particles from one location to another within mixture
- E.g. Inserting spatula into powder bed and lifting a portion to be deposited elsewhere

2) Shear
- Slip planes formed as unstable fractions collapse
- Mixing occurs along interfaces of shear/slip planes

3) Diffusive
- Occurs when a body of powder is lifted beyond its angle of repose and starts avalanching –> particles tumble over each other (micromixing)
- Differences in the velocity of powder layers can help to migrate particles from one layer to another
- Redistribution of individual particles by the random movement of the particles relative to each other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Segregation often occurs during ___

A

Powder transfer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Segregation occurs due to differences in

A

1) Particle size
2) Particle shape
3) Density

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Segregation results in

A

Loss of content uniformity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Segregation mechanisms

A

1) Percolation segregation
2) Elutriation segregation
3) Projection segregation
4) Feed/Heap segregation
5) Shear segregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Percolation segregation

A

Occurs when powder bed is subjected to vibration / movement
- E.g. Expansion of particle bed, particle movement (usually occurs during powder transfer)

Finer / denser particles will percolate to the bottom

Typically seen in:
1) Bin that vibrates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Elutriation segregation

A

Occurs when their is air stream rushing through powder bed –> sifts out lighter/finer particles (will follow direction of air stream)

Typically seen in:

1) Filling empty tube with powder
- Displaced air during filling –> push finer particles up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Projection segregation

A

Occurs when a powder bed is projected into the air –> heavier particles will be projected further due to larger inertial forces

Typically seen in:
1) Under the outlet of a horizontal belt conveyer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Feed/Heap segregation

A

Larger/Heavier particles will roll down heap of powder

Typically seen:
1) Charging bin/hopper

Can be overcome by:
1) Having larger opening to allow mass flow of powder

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Shear segregation

A

Occurs when 2 planes in a powder bed shear –> Finer particles of the top layer will fill the voids of the bottom layer

Typically seen when:
1) Powder flow down a slope

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Ordered mixing - What is it

A

Finer particles mixed with larger/coarser carrier particles
Finer particles coat carrier particles
Constituent particles are not independent of each other

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Ordered mixing - Application

A

Used for inhalation products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Ordered mixing - Segregation mechanisms

A

1) Ordered unit segregation
- Difference in size of carrier particles –> segregation of carrier particles
- Larger carrier particles will have more of the adsorbed component (i.e. more drug-rich)

2) Displacement segregation
- Addition of another component which may compete for carrier particle –> displaces adsorbed component

3) Saturation segregation
- Saturation of active sites on carrier particles
- Additional fine particles segregate via percolation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Geometric dilution

A

1) Take drug (small amount) & equivalent amount of excipient & blend
2) Take mixture & equivalent amount of excipient & blend
3) Repeat until all the excipient is used up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Shaped bin blenders - Types

A

1) V-cone, Y-cone

2) Double cone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Shaped bin blenders - Limitations

A

1) Tremendous shear involved when blending large amounts of powder
2) Large space/room needed to keep blender
3) Transfer of powder tends to be cumbersome, especially for large amounts

19
Q

Shaped bin blenders - Applications

A

1) Mainly for small scale use

2) Largely replaced by IBC blenders in pharmaceutical production

20
Q

Types of industrial blenders

A

1) High shear mixer
2) Paddle / Screw / Agitator mixer
3) Mechanofusion

21
Q

Common laboratory blenders

A

1) Drum/Barrel hoop blender
- Container is rotated along axis that is least symmetrical
- Uses roller that will roll container in circular path
- Efficient & flexible mixing chamber change

2) Turbula mixer
- 3D movement –> very effective mixing
- Most common laboratory blender
- Popular in pharmaceutical / R&D
- Best used for free-flowing particles

22
Q

Mixing process

A

Solid-solid mixing involves:

1) Expansion of powder bed
2) Application of 3D shear forces (e.g. rotation, vibration) to powder bed
3) Allow sufficient time to achieve random mix
4) Maintain random state
- Ensure no segregation occurs before ending mixing process

23
Q

Factors affecting mixing

A

1) % actives
- Decrease in % actives (especially < 1%) –> difficult to mix small component with large component –> mixing more difficult
- Overcome by:
• Reduce particle size –> increase no. of particles
• Dissolve/Disperse in liquid medium –> spray coat larger particle

2) Particle size
- Smaller particle size –> increase no. of particles per unit weight –> better mixing
- BUT Smaller particles tend to agglomerate (especially particles in micron range)

3) Particle size distribution
- Narrow size distribution –> less densely packed (more void space) –> better mixing BUT more prone to segregation, especially when other ingredients are incorporated
- Broad size distribution –> more densely packed –> poorer mixing (may clump up) BUT less prone to segregation

4) Particle shape
- Rounder particles easier to mix BUT more prone to segregation

24
Q

Test for blend homogeneity - Importance

A

Determine optimal mixing time

25
Q

Test for blend homogeneity - When to carry out

A

1) Development
2) Scale-up
3) Change blender

26
Q

Test for blend homogeneity - Important factors

A

1) Sample size
- Should be equivalent to unit dose
2) No. of samples
- Must be representative
3) Sampling device used

27
Q

Test for blend homogeneity - Sampling devices

A

1) Spoon
- Not precise
- Generally avoid (but may be used in labs / small scale)

2) Thief key
- Can be inaccurate
- Only takes sample from one point

3) Core/Slot sampler
- Able to take samples from 3-5 points
- Can sample along blend axis
- Improves accuracy
- Commonly used

28
Q

Test for blend homogeneity - Sample size

A

Should have sufficient sampling points

E.g. As many as 19 for 1000L IBC with thief key

29
Q

Process variables in blending

A

1) Loading method
2) End point
3) Scale up
4) Material characteristics

30
Q

Loading method

A

Loading methods:

1) Layering
- Split up each excipient and load one portion of largest excipient first, followed by other excipient(s) –> load active –> load largest excipient above active, followed by other excipient(s)
- Allows radial mixing (top-bottom mixing)
- More efficient –> reduces no. of revolutions to 10-20 revolutions

2) Side by side loading
- Requires side-by-side mixing
- Less efficient –> can take up to > 250 revolutions

Addition of lubricants

  • Generally added at end of mixing process
  • Overmixing –> cause waterproofing of drug (lubricants are generally hydrophobic)
31
Q

End point determination - Key measure

A

No. of revolutions

32
Q

Scaling up / Blending trials

A

Blending trials carried out to establish blending method

Carried out with:

1) Similar shaped bins
2) Smaller amounts of powder
- Volume of container in blending trials is 1/10 of volume of final container (1:10)

33
Q

Material characteristics

A 
Materials used (e.g. excipients, API) should be within reasonable specifications 
- For both blending trials &amp; large scale mixing

Hygroscopic actives/agents can absorb moisture from excipients –> can cause dramatic change in blend characteristics –> discharge problems & or balling

34
Q

Fill ratio / % Fill

A

Optimal: 60% (55 - 70%) (2/3 of container)

Too little fill

  • A lot of air space –> segregation can occur
  • Require greater no. of revolutions

Too much fill
- No/Little air space above powder –> no space for powder to rotate/roll around & mix

35
Q

Current trends

A

1) Containment
- Contained additions in blending room (minimize transfer)
- Contained sampling
- Milling blending modules - Integrated standard units (reduce contact with product)
- Non-GMP production areas
- Through-the-wall installations

2) Process analytical technology (PAT)
- In-line monitoring e.g. NIR

36
Q

Must ensure ___ during powder transfer

A

1) Good flow

2) No segregation

37
Q

Overcoming powder flow issues

A

Vibration

1) External vibration
2) Internal vibration

38
Q

External vibration

A

Frame vibration

IBC vibration

39
Q

Internal vibration

A

E.g. Vibroflow

40
Q

Limitations of vibration

A

1) Causes segregation

41
Q

Choice of external VS internal vibrator depends on:

A

1) Compaction
2) Segregation
3) Noise
4) IBC damage
5) Weighing system
- External vibration may damage weighing scale
6) Dosing capability
7) Product residue
- Internal vibrator may cause some product to be retained in container

42
Q

Key factors for bin: blending

A

1) Blend critical parameters
- No. of revolutions
- % fill
- Loading method
- Sampling method
- Formulation
2) Simple scale up process
3) Contained process

43
Q

NIR - Benefits

A

1) No operator contact - safety
2) No sampling error - no thief
3) Real time information
4) Multi-ingredient uniformity
5) Process understanding
6) Process finger-printing for scale up
7) Right first time
8) Fast release of blend - reduced cycle times

44
Q

NIR - Indicates good mixing when

A

Spectra are highly reproducible

Solids (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions