Powder Mixing

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Questions and Answers

What is the primary role of a fluidised bed mixer in powder mixing?

To reduce energy consumption

To subject powder to a flowing gas stream (correct)

To eliminate particle segregation

To increase the weight of the particles

What is the optimal loading ratio range for fluidised bed mixers?

35-45%

20-30% (correct)

50-70%

25-35%

Which factor is NOT a consideration for selecting a mixer based on safety?

Particle color (correct)

Energy consumption

Dust emission

Mixer speed

What might lead to segregation during powder mixing?

Differences in particle size and shape Signup and view all the answers

Which of the following is a concern related to the energy consumption of a mixer?

Continuous versus batch mixing Signup and view all the answers

What is the main aim of powder mixing?

To achieve a homogeneous distribution of the single components in the powder bulk Signup and view all the answers

Which of the following accurately describes dry mixing?

Mixing of powders without the addition of a liquid phase Signup and view all the answers

What factor does mixing affect in solid dosage forms?

The bioavailability of the drug Signup and view all the answers

What is the purpose of pre-mixing in powder mixing?

To prepare mixtures with less than 5% w/w drug before further deagglomeration Signup and view all the answers

What type of mixers are tumbler mixers suitable for?

For free flowing powders Signup and view all the answers

What is a primary advantage of using a Y-cone or cylinder mixer for powder mixing?

It is effective for adding lubricants and glidants. Signup and view all the answers

Which disadvantage is associated with convective mixers?

They create dead spaces where powder hardly moves. Signup and view all the answers

What is a major characteristic of impaction mixers?

They rotate blades at speeds of 2000-3000 rpm. Signup and view all the answers

How does the internal impeller in a convective mixer assist in the mixing process?

It moves groups of particles within the bulk. Signup and view all the answers

What is a disadvantage of using an impaction mixer?

The risk of shattering powder particles due to shear. Signup and view all the answers

Which type of mixer is noted for its less fine particle segregation?

Convective mixer Signup and view all the answers

Which type of tower mixer is rarely used for dry powder mixing?

Convective mixer Signup and view all the answers

What component can reduce particle segregation in Y-cone and cylinder mixers?

Internal impellers or prongs Signup and view all the answers

What is the main difference between diffusion and convection in mixing mechanisms?

Diffusion pertains to individual particles, while convection involves groups of particles. Signup and view all the answers

Which mixer type is primarily used for very cohesive, agglomerated powders?

High shear mixers Signup and view all the answers

In which situation would you likely employ the process of granulation?

When dealing with poor particle size distribution due to agglomeration. Signup and view all the answers

What does a 'perfect mix' imply regarding particle arrangement?

Each particle lies adjacent to a particle of another component. Signup and view all the answers

Which factor does NOT affect powder segregation?

Humidity of the environment Signup and view all the answers

What should be done to mitigate problems caused by particle size during mixing?

Mill components to achieve a structural mix. Signup and view all the answers

What does a probabilistic chance of 1 in 4 mean when selecting two particles from a mixture?

There is a 25% chance of selecting two particles of the same type. Signup and view all the answers

What is the purpose of testing for drug content uniformity?

To analyze random samples for variations in drug content. Signup and view all the answers

Why is it important to control the crystallization process regarding particle shape?

To produce excipients with shapes similar to the drug. Signup and view all the answers

Study Notes

MPharm Programme: Powder Mixing

Powder mixing is the treatment of two or more powder components so each particle of one component is in contact with one of each additional component.
The aim is to achieve a homogenous distribution of components in the bulk powder.
Components of a powder mix include different powders (drugs and excipients), different particle size fractions of the same powder.
Powder mixing is crucial for granulation, tablet making, direct compression, capsule/sachet filling, and vial filling for injections.
Different properties of drugs and excipients affect mixing, including homogeneity of drug distribution in dosage forms, mechanical properties (e.g. of tablets), and drug bioavailability.

Mixing Terminology

Dry mixing: powders mixed without liquid additions
Wet mixing: powder mixed with a liquid binder (granulation)
Pre-mixing: used for mixtures with less than 5% w/w drug, followed by further deagglomeration (e.g., sieving).
Post-mixing: adding an external phase (e.g., lubricant or glidant) with short mixing times (3-5 minutes).

Mixer Types

Tumbler mixers: rotating vessels, prone to particle segregation, but internal impellers/prongs can reduce this. Useful for adding lubricants and glidants to granules.
Cube, cone and V mixers: (illustrated)
Turbula mixer: (illustrated)
Double cone mixer: (illustrated)
Convective mixers: fixed vessel with an internal impeller, less prone to fine particle segregation but have dead spaces, adhesion to blades, and shear forces that can shatter particles.
Planetary mixing: (illustrated)
Nautamixer: (illustrated)
Impaction & high shear mixers: high-energy input, blades rotating at high speeds (2000-3000 rpm) in static vessels. Break up aggregates, often used after tumbling mixing.
Impaction mixer: (illustrated)
Fluidized bed mixers: powders subjected to a flowing gas stream; weight of particles is counterbalanced by buoyancy, increasing particle mobility and efficiency.

Choice of Mixer

Physical Considerations: More space is needed, optimal loading ratio needed with respect to vessel volume (tumbling mixers – 25-35%, convective mixers – 50-80%, fluidised bed mixers – 20-30%). Need to consider particle distribution, limit particle attrition & overmixing, and temperature change.
Economic and Safety Considerations: Energy consumption, mixing time, continuous vs. batch mixing, time to fill, empty, and clean, dust emission, explosion hazard (electrostatic charging), surfaces/mixer speed, relative humidity.

Mixing Mechanisms

Expansion: Allows movement of particles
Agitation: Ensures sufficient period for mix.
Avoidance of segregation
Maintenance of adequate mix
Particle movement: Diffusion (random), convection (transfer of groups of particles), shear (sliding particle layers).
Mixer design determines which mechanism is dominant (e.g., simple tumbling mixers - free flow, high shear mixers - cohesive powders).

Interactive Powder Mixtures ('Ordered Mixtures')

Cohesive fine powders (<20 µm), coarse powders (coater/carrier units).
Interparticulate forces, improves homogeneity.
Ordered units have a definable size range.

Stable Powder Mixtures ('Ordered Mixtures')

Vibrating on a sieve (seeding).
Results: Segregation: ordered unit segregation (size difference), displacement segregation (3rd component), saturation segregation (limited surface sites).

Free-flowing Mixtures ('Random Mixtures')

No interparticulate forces, particles move freely.
Random distribution (governed by stochastic/statistical process).
Complete random mixture only if all components are identical in size, shape, and density.
Median size > 20 µm, used for direct compression.

Perfect/Random Mixtures

Each particle in a 'perfect mix' lies adjacent to another particle from a different component.
Random mix: maximum disorder - no way to predict particle type from neighbour.

Factors Affecting Segregation

Particle size, density, shape
Electrostatic charging, powder handling.

Particle Size Effects

Large particles give poor distribution
Particle size reduction gives good distribution.
Particle agglomeration gives poor distribution.

Testing Drug Content Uniformity in Powder Mix

Random samples, analysis of drug content.
Inspection: standard deviation, coefficient of variation
Comparing with pharmacopoeial tests.
Effect of mixing variables.

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Description

Test your knowledge on the principles of powder mixing as part of the MPharm program. This quiz covers important concepts such as dry mixing, wet mixing, and the significance of homogenous distribution of components. Gain a better understanding of the role of powder mixing in pharmaceutical applications.