Preformulation - mixing Flashcards
What is the definition of mixing?
- Mixing is a unit operation in which a uniform mixture is obtained from two or more components, by dispersing one within the other.
- It is a process that involves manipulating a heterogeneous
physical system, with the intent to make it more homogeneous
What is the importance of mixing?
- To obtain homogeneity and dose uniformity = efficacious & safe
- To produce dispersion.
- To achieve reproducibility during manufacture.
- To achieve efficiency and cost-effectiveness.
What are the three types of mixture?
- Positive mixture
- Negative mixture
- Neutral mixture
Describe positive mixture.
– Mixes spontaneously, energy input required to separate components.
– Miscible fluids (e.g. ethanol + water, gases).
Describe negative mixture.
– Segregates spontaneously, energy input required to mix and keep mixed.
– Immiscible phases (e.g. oil + water, suspensions).
Describe 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)
What are the three mechanisms of mixing solids?
- Convective mixing
- Shear mixing
- Diffusive mixing
Describe convective mixing.
– Redistribution of large groups of particles.
– Large degree of mixing in short period of time.
Describe diffusive mixing.
– Powder bed dilation, air introduced into powder bed during mixing.
– Particles move into air spaces under gravity or mechanical forces
Describe shear mixing.
– Velocity differences between layers of particles, layers of particles slide over one another.
– Mixing at interface between layers
Which mechanism predominates and the extent of which each occurs depends on what?
o Mixer type
o Mixing process conditions (e.g mixer load, speed)
o Particles characteristics
o Flowability of the components
As perfect mixing is unattainable what are the other alternatives?
- Random mixing
- Ordered mixing
Describe a random mixture.
A mixture in which the
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
Describe 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.
What are the main challenges with mixing powders?
Homogeneity difficult to achieve - especially when mixing small amounts into large bulk.
Demixing - segregation of components due exceeded blending times.
Overmixing - prolonged mixing degrades material properties (e.g. particle size, charge, surface texture).
