Greco Lecture 5: Mixing and Granulations

Question 1

What is the aim of mixing?

Answer 1

Obtain a homogenous distribution of two or more components (without physical or chemical changes occurring)

Question 2

What is a positive, negative, neutral mixture?

Answer 2

1. Postive: materials that mix spontaenously and irreversibly
2. Negative: materials that do not mix and separate
3. Neutral: Materials that separate nor to mix

Question 3

If there’s more particles in a dose, what is that more likely to mean?

Answer 3

Content will mirror ratio in the mixture

Question 4

What is segregation and what are the factors that affect it?

Answer 4

1. The opposite of mixing (de-mixing)
2. Factors are:
   - Densities
   - Shapes
   - Size

Question 5

Why can segregation be a problem when forming tablets?

Answer 5

1. First tablet may be 100% API (smaller molecules)

2. Second tablet may be 100% excipients (larger molecules)

Question 6

What is the process of checking mixture with time?

Answer 6

1. Powder a mixture
2. Take samples from different regions of the mixer
3. Measure the content ratio of the API to the excipients
4. Calculate the standard deviation of the sample and plot it verses time
5. Standard deviation will start decreasing the more the product gets mixed

Question 7

What are the sorts of equipment you need for mixing?

Answer 7

Tumbling mixers
1. Y-Cone mixer

2. Rotating cube
3. Double cone
4. Oblique cone

Mixer granulators
5. Agitator mixers

Question 8

What is granulation?

Answer 8

The process when a homogenous mixture of primary particles form larger still homogenous particles called granules

Question 9

What are the main reasons behind granulation?

Answer 9

1. Improve particle flow rate (reduced dust generation)
2. Prevent segregation
3. Improve compaction (occupy less volume)

Question 10

Describe the wet granulation process?

Answer 10

1. The powders are mixed with a granulating fluid that’s usually volatile
2. Formation of a damp mass that’s dried to form granules
3. The mass is forced through a sieve
4. Add your lubricant and compress and you have your tablet

Question 11

Describe the dry granulation process?

Answer 11

1. A pressure is applied
2. Intermediate product is broken
3. Sieving- desired particle size
4. Add lubricant and compress it

Question 12

What are the wet granulation mechanisms?

Answer 12

1. Adhesion and cohesion in immobile films
2. Interfacial forces in mobile films
3. Solid bridges (hardening of binders, or crystallisation of dissolved substances)
4. Attractive forces between particles

Question 13

What are the steps of forming granules from wet granulation?

Answer 13

1. Nucleation: small particles form balls
2. Transition
3. Ball growth: particles attach to the nucleus to make the ball grow bigger

Question 14

What are the granulation mechanisms of dry granulation?

Answer 14

1. Attractive forces between solid particles

2. Solid bridges (by partial melting)

Question 15

How do shear granulators form granules?

Answer 15

1. Mixing
2. Formation of damp mass
3. Pushed through a sieve: forms granules
4. Drying

Question 16

How do high speed granulator machine mixers work?

Answer 16

1. Chopper is within the machine that breaks the powder and starts mixing
2. Impeller spins the powder to mix
3. Add granulating fluid