Mixing Flashcards
Definition of mixing ?
- a unit operation in which a uniform mixture is obtained from two or more components, by dispersing one within the other
- involves manipulation a heterogenous physical system, to make it more homogenous
Importance of mixing ?
- To produce dispersion.
• To achieve reproducibility during manufacture.
• To achieve efficiency and cost-effectiveness - To obtain homogeneity and dose uniformity = efficacious & safe
Types of mixture ?
- positive mixture
- negative mixture
- neutral mixture
What is a positive mixture ?
- Mixes spontaneously, energy input required to separate components.
– Miscible fluids (e.g. ethanol + water, gases)
What is a negative mixture ?
- Segregates spontaneously, energy input required to mix and keep mixed.
– Immiscible phases (e.g. oil + water, suspensions).
What is neutral mixture ?
- Components neither mix nor segregate spontaneously, energy input required to mix or segregate components.
– Once mixed, mixture remains stable (e.g. powders, pastes)
3 Mechanisms of mixing solids ?
- Convective mixing
– Shear mixing
– Diffusive mixing
Mechanisms of powder mixing ?
- Convective mixing
- Diffusive mixing
- Shear mixing
What is convective mixing ?
- Redistribution of large groups of particles.
– Large degree of mixing in short period of time.
What is diffusive mixing ?
- Powder bed dilation, air introduced into powder bed during mixing.
– Particles move into air spaces under gravity or mechanical forces
What is shear mixing ?
- Velocity differences between layers of particles, layers of particles slide over one another.
– Mixing at interface between layers.
What to consider when deciding which one predominates ?
- Mixer type
o Mixing process conditions (e.g mixer load, speed)
o Particles characteristics
o Flowability of the components
What is ideal / perfect mixing ?
- practically no mixing process will never yield perfect mixing.
What is acceptable mixing ?
since perfect mixing is unattainable, possible other alternatives can be:
1. Random mixing
2. Ordered mixing
What is a random mixture ?
- probability of finding a particle of any component is the same at all locations and equal to the proportion of that component in the mixture as a whole
What is an ordered mixture ?
- When micronized particle become adsorbed on surface of larger carrier particles.
• Adsorbed and carrier particles move inter-dependently.
• Minimal segregation.
• Useful for mixing potent drugs.
• Pharmaceutical powder mixtures likely partly ordered.
What are the main challenges with mixing powders ?
- Homogeneity difficult to achieve (esp. when mixing small amounts into large bulk)
- Demixing (segregation of components due to exceeded blending times )
- Overmixing (prolonged mixing degrades material properties (e.g. particle size, charge, surface texture)
What are the 2 divisions of solids depending on flow properties ?
- cohesive materials
- non- cohesive materials
What is cohesive mixing ?
- characterized by their resistance to flow through openings for e.g. wet clay.
- Fine particles are more cohesive.
What are non-cohesive materials ?
- flow readily such as grain, dry sand etc.
- Mixing of cohesive materials is more difficult due to formation of aggregates and lumps.
What are the physical properties affecting mixing ?
-
Material density: Denser material will sink through the lighter one
• Particle size: Differences in particle size is the main cause of segregation
• Particle shape: ideal particle is spherical greater flowability
• Particle attraction : influence aggregation
What is segregation / demixing ?
- Reverse process of mixing.
Why do powders segregate ?
• difficulty of mixing is mainly due to differences in particle sizes.
• Mixture made of particles of different dimensions will always tend to separate.
• Segregation is a function of of size, density
and shape of the particles.
5 Causes of segregation ?
- Vibrations during manufacturing can demix fine particles by diffusion
- Particle size non-uniform.
– Particle density non-uniform.
– Spherical shape (free-flowing).
– Powders are not free flowing
Methods of minimising segregation ?
- Uniform particle size.
• Ordered mixture (e.g. granulation).
• Select excipients of similar density.
• Use premixing - Reduce vibration.
• Use appropriate mixer.
Mechanisms of segregation
- Percolation separation: Small particles fall through voids (e.g.in cereal box).
- Trajectory segregation: Larger particles go further as they have more mass based inertia
- Elutriation segregation: ‘Dusting out’—fine particles settle on top after motion has ceased.
