Preformulation - Mixing

Question 1

What is homogenous?

Answer 1

Each component particle lies as nearly as possible in contact with a unit of each other component

Question 2

What are the different types of mixtures?

Answer 2

Positive
Negative
Neutral

Question 3

What is a positive mixture?

Answer 3

Mixes spontaneously, energy input not required to separate components

Question 4

What is positive mixture for?

Answer 4

Miscible fluids

eg. ethanol, H2O + gases

Question 5

What is a negative mixture?

Answer 5

Segregates spontaneously, energy input required to mix + keep mixed

Question 6

What is a negative mixture for?

Answer 6

Immiscible phases

eg. oil, H2O + suspensions

Question 7

What is a neutral mixture?

Answer 7

Components neither mix nor segregate spontaneously, energy input required to mix or segregate components

Question 8

What is a neutral mixture for?

Answer 8

Powders + pastes

Question 9

What happens to a neutral mixture once it has been mixed?

Answer 9

It remains stable

Question 10

What are the mechanisms for liquids?

Answer 10

Bulk transport
Turbulent mixing
Molecular diffusion

Question 11

Describe bulk transport

Answer 11

Redistribution of large amount of liquid

Large degree of mixing in short period of time

Question 12

Describe turbulent mixing

Answer 12

Groups of molecules move with constant velocity changes

Question 13

Describe molecular diffusion

Answer 13

Movement of molecules down concentration gradient

Question 14

What are the mechanisms for solids?

Answer 14

Connective mixing
Shear mixing
Diffusive mixing

Question 15

Describe connective mixing

Answer 15

Redistribution of large groups of particles

Large degree of mixing in short period of time

Question 16

Describe shear mixing

Answer 16

Velocity differences between layers of particles = layers slide over one another
Mixing at interface between layers

Question 17

Describe diffusive mixing

Answer 17

Powder bed dilation, air introduced into powder bed during mixing
Particles move into air spaces under gravity or mechanical force

Question 18

What is needed for mixing powders?

Answer 18

Good powder flowability

Question 19

Why is free-flowing powder easy to mix?

Answer 19

Monosize + low-energy

Question 20

What can free-flowing powder by susceptible to?

Answer 20

Segregation if different size or density

Question 21

What may be needed when mixing cohesive powder?

Answer 21

High-energy de-agglomeration

Question 22

What is the equation used to determine if mixing is adequate?

Answer 22

σR = √ p(1-p)
————
n
σR = theoretical standard deviation of random mixture
p(1-p) = proportion of drug/tracer in mixture
n = total no. of particles in mixture

Question 23

What happens the longer you mix a mixture?

Answer 23

More homogenous it becomes

Question 24

What is the mixing index?

Answer 24

σR

Question 25

What are powders?

Answer 25

NOT perfect mixtures | = settle for random mixtures

Question 26

What is the scale of scrutiny?

Answer 26

Amount of powder per sample for assessing extent of mixing | Amount = 1 dosage unit

Question 27

What is an ordered mixture?

Answer 27

Micronized particle adsorbed on surface layer of larger carrier particles Adsorbed + carrier particles move inter-dependently

Question 28

What is useful about ordered mixture?

Answer 28

Minimal segregation

Question 29

What is an ordered mixture useful for?

Answer 29

Potent drugs

Question 30

What are pharmaceutical powder mixtures likely to be?

Answer 30

Partly ordered

Question 31

When is segregation likely?

Answer 31

Particle size non-uniform Particle density non-uniform Spherical shape (free-flowing)

Question 32

What are the mechanisms for segregation?

Answer 32

Percolation separation Trajectory Elutriation segregation

Question 33

What is percolation separation?

Answer 33

Small particles fall through voids

Question 34

What is trajectory?

Answer 34

Larger particles go further as they have more mass based inertia

Question 35

What us elutriation segregation?

Answer 35

"Dusting out" fine particles on top after motion has increased

Question 36

How can you minimise segregation?

Answer 36

``` Uniformed particle size Ordered mixture Select excipients of similar densities Reduce vibration Single-station operation - eg. multiple processes in same equipment ```

Question 37

Why is mixing important?

Answer 37

Dosage uniformity: efficacious + safe Reproducibility during manufacture Variability inevitable Active content commonly +/- 5% of label claim

Question 38

What variability is inevitable?

Answer 38

Error tolerance depends on product + application | High uniformity required for very potent drugs