Lecture 10 - Particle Science II

Question 1

What is the aim of mixing?

Answer 1

to obtain a homogenous distribution of two or more components (without physical or chemical changes occuring)

Question 2

When is mixing particularly important?

Answer 2

when very active drugs are employed (<1%), this is to ensure uniformity of active ingredients

and when you have a small therapeutic index

Question 3

What are positive mixtures?

Answer 3

Materials that mix spontaneously and irreversibly

Question 4

Examples of positive mixtures?

Answer 4

gases and liquids

Question 5

What are negative mixtures?

Answer 5

the components tend to separate

Question 6

Examples of negative mixtures?

Answer 6

Suspensions (solid in a continuous phase)

Question 7

What are neutral mixtures?

Answer 7

Components neither tend to separate nor mix

Question 8

Examples of neutral mixtures?

Answer 8

powders = we need energy to achieve mixing

Question 9

What does having more particles present do?

Answer 9

the more particles present in a dose, the more likely it is that the content will mirror the ratio in the mixture

Question 10

What does a low proportion of a component in a mixture mean?

Answer 10

the lower the proportion of a component, the more difficult it is to achieve the same (correct) amount in each sample

Question 11

What are other factors that affect mixing?

Answer 11

particle size, shape

density

flowability

ratio between different components

mixing time

electrostatic interactions

total volume of powders being mixed

friability of the material

humidity

Question 12

What is segregation?

Answer 12

the opposite of mixing

Question 13

What is segregation due to?

Answer 13

the fact that powders have different densities, shapes and sizes

Question 14

How can we check mixing with time?

Answer 14

Take samples from different regions within the mixture and calculate the relative ratio of the components

we then calculate the standard deviation of the samples and plot it against time

Question 15

What are tumbling mixers?

Answer 15

good for working with granules and free flowing powders

when used at the correct speed there is turbulence and dilation of the powder bed, and mixing by sheering

Question 16

What is a mixer granulator?

Answer 16

a combination system which mixes granules, the base plate spins ar a high speed, forcing the material up the wall, which then collapses

provides dilation of the powder bed and the speed creates sheering forces within the system

Question 17

What else is in a mixer granulator?

Answer 17

a blade on the side to break up masses formed

Question 18

What are agitator mixers?

Answer 18

they have a motion blade and there is mixing of components due to convection

Question 19

What is granulation?

Answer 19

the process in which homogenous mixtures of primary powder particles form larger, still homogenous particles called granules

Question 20

What does granulation improve?

Answer 20

powder flow, compaction and prevents segregation

Question 21

How does granulation prevent segregation?

Answer 21

the larger particles have a uniform consistency so smaller particles will not fall to the bottom

Question 22

How does granulation improve compaction?

Answer 22

when we make a tablet, granules flow well in the system and flow well into the dye we use to compact them

Question 23

What other reasons are there to use granulation?

Answer 23

It reduces the generation of dust (important for toxic compounds)

whilst hygroscopic powders form cakes, granules retain their flowability even after absorbing moisture

granules occupy less volume

Question 24

What is coalescence?

Answer 24

particles coming together to form larger ones

Question 25

What are the steps of granulation?

Answer 25

coalescence

breakage

abrasion transfer

layering

Question 26

What happens in wet granulation?

Answer 26

the powders are mixed with a granulating fluid and the mass is forced through a sieve

we then dry and sieve again then lubricate and compress to form a tablet

Question 27

What is the wet granulation mechanism?

Answer 27

adhesion and cohesion forces in immobile films

interfacial forces in mobile films

solid bridges formed

attractive forces between particles

Question 28

What do adhesion and cohesion forces mean?

Answer 28

interparticulate distance decreases

increase in the contact area

Question 29

What are solid bridges?

Answer 29

hardening binders or crystallisation of dissolved substances

Question 30

What is a high speed mixer/granulator?

Answer 30

components are added and there is an impellor, which spins at a high speed so powder goes up the side and tumbles down

the powder bed is expanded and mixed

once the powder is mixed you add liquid to form granules

chopper bladder to chop up masses

Question 31

Benefit of high speed mixer?

Answer 31

mixing, massing and granulation all in one kit

Question 32

What is a fluidised bed granulator?

Answer 32

it has an inlet of air and a nozzle which is the granulating liquid

powder inside are mixed and granulated at the same time

exhaust filters and air goes out of the system

need to optimise this kit to make granules

Question 33

What is the process of dry granulation?

Answer 33

a pressure is applied to the mixed drug and excipients

partially melted components and fuse then - the intermediate product is broken

sieving, lubrication and compression

Question 34

Dry granulation mechanisms?

Answer 34

attractive forces between solid particles

solid bridges (by partial melting)

mechanisms of granule formation

Question 35

Advantage of dry granulation?

Answer 35

not using liquid so there is no need to dry

less steps than wet granulation