Powder Mixing

Question 1

What is the importance of powder mixing?

Answer 1

All solid dosage forms
Content uniformity
Therapeutic efficacy
Patient safety

Question 2

What are the challenges of powder mixing?

Answer 2

1) Homogeneity difficult to achieve
Especially when mixing small amounts into large bulk
2) Demixing
Segregation of components over time.
3) Overmixing
Prolonged mixing degrades material properties (e.g.particle size, charge, surface texture).

Question 3

What are the 3 types of mixtures?

Answer 3

Positive mixture- mixes spontaneously
Negative mixture- Segregates spontaneously
Neutral mixture- Neither mixes nor segregates spontaneously

Question 4

What can the three types of mixtures be made into?

Answer 4

Perfect mixture- Completely homogenous
Random mixture- 80% homo, low content variability
Ordered mixtures- small particles adsorbed on to larger ones, inter-dependently move

Question 5

How is powder homogeneity assessed and what type of mixture is it?

Answer 5

It is assessed using a statistical approach
Robust sampling is important

Random

Question 6

What is ‘Sample size’ and ‘Scale of scrutiny’?

Answer 6

Sample size: Amount of powder to sample

Scale of scrutiny: The most suitable sample size, equivalent to the amount of mixture present in one dosage unit (e.g. mass of a tablet)

Question 7

What are the 5 essential characteristics of mixers?

Answer 7

1) Homogeneity without degradation
2) Short mixing time
3) Reproducible
4) High yield
5) Cleanable

Question 8

What are desirable features of mixers?

Answer 8

1) Versatile
2) Scalable
3) Small footprint (size)
4) Integration within manufacturing process (downstream process)-flow in factory
5) Cost and energy efficient
6) In-line motoring- info about mixer (70% mixed)
7) Environmental controls-more control and stability

Question 9

What are the 5 types of mixture?

Answer 9

Tumbling 
Agitator
Shear
Fluidised Bed
Static

Question 10

What is a tumbling mixer?

Answer 10

Rotating vessel contains

powder

Question 11

What is an agitator/nauta mixer?

Answer 11

Low-shear rotating paddles move powder

Question 12

What is a shear mixer?

Answer 12

High-speed rotating blade split agglomerates

Question 13

What is a fluidised bed mixer?

Answer 13

High speed air disperses particles

Question 14

What is a static mixer?

Answer 14

Particles flow through static mixing elements

Question 15

What are the mechanisms of the a tumbling mixer?

Answer 15

Particles set in motion by rotation of a vessel
Mainly shear and diffusive mixing
Performance affected by:
Fill volume- max 50-60%
Residence time- how long it mixes
Rotation speed
Inclination angle of mixer

Question 16

What are the three different types of mixing?

Answer 16

Convective mixing: Mixing large groups of particles(move in groups)
Shear mixing: (rubbing )
Mixing at the interface between large groups of particles
Diffusive mixing:
Mixing within large groups of particles

Question 17

What are the three types of tumbling mixer?

Answer 17

Rotating cube
Double cone
V-cone mixer

Question 18

What are the characteristics of shear mixers?

Answer 18

High-velocity rotating blades
High shear forces
Breaks up agglomerates
Shear and diffusive mixing
Unsuitable for friable materials

Question 19

What is a nauta/agitator mixer?

Answer 19

Contains a rotating screw in a conical vessel

Screws rotate axially and in an orbital motion

Question 20

What is a fluidised bed mixer?

Answer 20

High-velocity air is passed through the bottom of the powder bed, causing particles to float/mix
Suitable for medium-density friable powders
Free-flowing powder, not sticky ones

Question 21

What is a static mixer?

Answer 21

No moving parts

Powder flows through motionless mixing elements

Question 22

What are the practical considerations?

Answer 22

Ensure that the mixer matches the material properties
Ensure fill volume and mixing mechanism
Determine mixing time
Statics cause clumping, (electrostatic attractions between particles), you can coat the particle to dissipate statics by earthing mixture
Use geometric-pre blending (1:99 drug to excipient, begin with 50:50- 25:25)