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Pharmaceutics > Preformulation - Mixing > Flashcards

Preformulation - Mixing Flashcards

1
Q

What is homogenous?

A

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

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2
Q

What are the different types of mixtures?

A

Positive
Negative
Neutral

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3
Q

What is a positive mixture?

A

Mixes spontaneously, energy input not required to separate components

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4
Q

What is positive mixture for?

A

Miscible fluids

eg. ethanol, H2O + gases

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5
Q

What is a negative mixture?

A

Segregates spontaneously, energy input required to mix + keep mixed

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6
Q

What is a negative mixture for?

A

Immiscible phases

eg. oil, H2O + suspensions

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7
Q

What is a neutral mixture?

A

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

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8
Q

What is a neutral mixture for?

A

Powders + pastes

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9
Q

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

A

It remains stable

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10
Q

What are the mechanisms for liquids?

A

Bulk transport
Turbulent mixing
Molecular diffusion

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11
Q

Describe bulk transport

A

Redistribution of large amount of liquid

Large degree of mixing in short period of time

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12
Q

Describe turbulent mixing

A

Groups of molecules move with constant velocity changes

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13
Q

Describe molecular diffusion

A

Movement of molecules down concentration gradient

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14
Q

What are the mechanisms for solids?

A

Connective mixing
Shear mixing
Diffusive mixing

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15
Q

Describe connective mixing

A

Redistribution of large groups of particles

Large degree of mixing in short period of time

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16
Q

Describe shear mixing

A

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

17
Q

Describe diffusive mixing

A

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

18
Q

What is needed for mixing powders?

A

Good powder flowability

19
Q

Why is free-flowing powder easy to mix?

A

Monosize + low-energy

20
Q

What can free-flowing powder by susceptible to?

A

Segregation if different size or density

21
Q

What may be needed when mixing cohesive powder?

A

High-energy de-agglomeration

22
Q

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

A

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

23
Q

What happens the longer you mix a mixture?

A

More homogenous it becomes

24
Q

What is the mixing index?

A

σR

25
Q

What are powders?

A

NOT perfect mixtures

= settle for random mixtures

26
Q

What is the scale of scrutiny?

A

Amount of powder per sample for assessing extent of mixing

Amount = 1 dosage unit

27
Q

What is an ordered mixture?

A

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

28
Q

What is useful about ordered mixture?

A

Minimal segregation

29
Q

What is an ordered mixture useful for?

A

Potent drugs

30
Q

What are pharmaceutical powder mixtures likely to be?

A

Partly ordered

31
Q

When is segregation likely?

A

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

32
Q

What are the mechanisms for segregation?

A

Percolation separation
Trajectory
Elutriation segregation

33
Q

What is percolation separation?

A

Small particles fall through voids

34
Q

What is trajectory?

A

Larger particles go further as they have more mass based inertia

35
Q

What us elutriation segregation?

A

“Dusting out” fine particles on top after motion has increased

36
Q

How can you minimise segregation?

A 
Uniformed particle size
Ordered mixture
Select excipients of similar densities 
Reduce vibration
Single-station operation - eg. multiple processes in same equipment
37
Q

Why is mixing important?

A

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

38
Q

What variability is inevitable?

A

Error tolerance depends on product + application

High uniformity required for very potent drugs

Pharmaceutics (21 decks)

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