Mixing Flashcards
What is Convection mixing?
Convection: macroscopic mixing, relatively quick (extended mixing time is necessary to achieve random mix)
Transfer of large group of particles through the powder bed
Values of M
- beginning of mixing
- optimum mixing time
- longer mixing time
-beginning - M low as SACT is high
- optimum - M~1 as SACT similar to SR
- M>1 - demixing/mixing occur
In the case of components with a tendency to separate, what factor is crucial to know in order to determine the quality of the mixture?
In this case, the mixing time is crucial in determine the quality of the mixture
When might segregation occur with an ordered mixture?
- If coarse particles differ in size
- If active sites on coarse particles surface compete with other materials than the fine particles
- if coarse particles are not sufficient to interact with the finer ones
- External mechanical forces (e.g. vibration) reduce the surface attraction energy
What is Ordered mixing?
What is it driven by? When does this drive increase?
How much the degree of mixing compare to a other types of mixtures?
- Ordered mixing: components are not independent of each other, resulting in a “spontaneous” degree of order in the mix
- It is driven by interactions and cohesive/adhesive forces between components
- e.g. the higher surface of smaller particles (thus the higher attractive forces) is greater than the gravitational force to separate the components
- It might achieve a superior degree of mixing to that of random mix
Positive mixtures are what?
What problems arise from manufacturing processes with these mixtures?
What are the energy requirements?
Positive mixtures: components mix spontaneously and irreversibly by diffusion (almost perfect mix achieved) e.g. miscible liquids.
These materials do not present any problem in manufacturing processes.
No energy required with unlimited mixing time. To shorten the mixing time and obtain the desired degree of mixing, input energy can be given to the process.
Planetary mixers for mixing of semi-solids present what issues?
What type of mixing mechanism must the mixers produce?
Other than semi-solids, what else is mixed using planetary mixers?
Flowing issues compare to fluids
High risk of “dead spot” with non-mixed materials
-Mixers must produce high shear mixing: diffusion mixing cannot occur
High viscous fluids are mixed using the same mixers as semi-solids
What type of mixing is preferred for particles with a tendency to aggregate? Why?
High shear mixing used to used to break up aggregates (and guarantee mixing at particulate level).
Agitator mixers:
Describe the motion
What do agitator mixers mix?
Via what mechanism?
Blade (or paddle) motion to mix powders through convection mechanisms
Mixing index?
The Mixing index compares the content standard deviation from a samples under investigation (SACT) with the one of a fully random mix sample (SR):
The simplest form is M=SR/SACT
Beginning of mixing: M is low as high SACT
End of mixing: M is ~1 as SACT similar to SR
Propeller mixing for liquids:
Describe how the mixing occurs
What do you not want to happen and how do you suppress that?
Angle blades to promote fluid movement in both axial and radial direction
Formation of vortex (centrifugal forces) is suppressed by:
Offset angle mounting (A)
Vertical baffles (B)
Describe how mixing of solids is done
What must you get right when filling the mixture?
How do you keep track of everything?
Sequential addition of components until all materials has been added
E.g. initial mix of active component with a diluent, and other excipients added at a later stage
Volume of powder adequate for the mixer used
Do not under- or over-fill
Follow the mixing time by analysing the mixture composition
Problems for extended mixing time can be identified e.g. segregation
How does particle size and density affect powder segregation?
How does particle shape affect powder segregation?
Particle size effects:
Smaller particles tend to fall through the voids between larger particles
Particle density effects:
The denser particles tend to move downwards (gravity). IF particles are denser and smaller, the segregation is higher
Particle shape effects:
Spherical particles are easier to mix, hence segregate more easily than non-spherical particles
Non-spherical particles have greater surface area to weight ratio: increase cohesive effects
Tumbling mixers:
What do they mix? What do they look like and how do they work?
What is the typical powder weight range used?
What volume of powder should occupy the mixer?
When are tumbling mixers used?
What kinds of mixing do they make happen?
Mix blending granules or free-flowing powders
Have many different designs
Might have intermediate containers e.g. feeder for a tablet machine
Generally rotate about an axis with controlled speed
Typical powder weight used range from 50g to 100kg
For best performance, the powder mixture should occupy from ½ to ⅔ of the mixer volume
Generally used in the blending of excipients prior tabletting
With a correct speed set, shear mixing will occur
With movement the powder dilates, allowing particles to move under gravitational force: diffusive mixing occurs
If there is an increase in particle size of a component in the mixer, how would you resolve this issue?
What are the consequences of this solution?
A solution could be to:
increase the dose unit (hence the scale of scrutiny), but this will impact on:
the number of particles per dose unit
the proportion of the active component
Turbine mixers are suitable for mixing what?
How are the blades designed to move?
How does the mixer work?
What do high shears in this mixer do?
Suitable for viscous fluids
Blades are designed to push the fluid radially, with no vertical motion
Fluids are forced through perforated diffuser rings at high velocity, producing high shears
In case of immiscible fluids, with sufficiently small orifices and high velocity, high shears enable the generation of droplets to obtain a stable dispersion
How does powder segregation occur in a random mix?
Already formed random mix might change to a non-random mix (or random mix never achieved)
Segregation is mainly caused by particles differing in: size, shape, density, and surface properties.
Scale of scrutiny - define
The scale of scrutiny is the amount of material (in weight or in volume) used to test the QUALITY of a mixture:
To minimise the amount of variation of ingredients in a powder can be minimised by
- Understanding mixing mechanism principles
- Identifying the criteria to select powders e.g. particle size-
- Knowing the final dosage form properties and manufacturing processes
Negative mixtures
Negative mixtures: components tend to separate, and they need a constant input energy to maintain the desired dispersion e.g. suspension of solid particles in low viscosity solution.
The viscosity of the solution slow down the separation process e.g. cream, viscous suspension
Negative mixtures require a higher degree of mixing efficiency
Ordered mixing
Fine and coarse powder sizes
And structure
Coarse powder: 0.1-1mm
Fine powder: 50-100um
adhesion of fine to coarse powder
redistribution and exchange of fine powder
ordered mixture made
