Pharmaceutics: Powder Mixing Flashcards
What is the aim of powder mixing?
To distribute drug and excipient particles uniformly among one another (homogeneity of contents)
Effect of powder mixing in the long run?
Affects
- content uniformity in final pharmaceutical product
- the therapeutic efficacy
- patient safety.
Out of gases, solids and liquids, which is more difficult to obtain homogeneity with?
Solids because they don’t flow as freely as fluids (gases and liquids)
What are the challenges faces when mixing powders?
1) difficulty obtaining homogeneity when mixing a small amount into a large bulk
2) segregation of particles
3) over-mixing which degrades particles hen affecting their properties.
Types of powder mixtures?
1) positive - mix spontaneously
2) neutral - don’t mix/segregate spontaneously
3) negative - segregate spontaneously
Types of mixtures that can be achieved?
1) perfect - completely homogeneous (unattainable with powders)
2) random - close to complete homogeneity with free-flowing particles of similar size and density.
3) ordered - small particles adsorbed onto larger ones and move inter-independently. Cohesive particles of different sizes.
What type of mixtures are powders and what type of mixtures do they achieve?
Powders are neutral mixtures and when they form homogeneous mixtures, it is random type of mixture.
How do you asses the homogeneity of random mixtures?
doing statistical calculations and sampling small amounts from different parts of the mixture and analysing their composition.
How can you reduce variances when sampling?
Take larger samples
What are 5 essential performance characteristics of equipment’s used to mix powders?
1) homogeneity without degradation
2) short mixing time
3) reproducible
4) high yield
5) cleanable
7 desirable features when choosing equipment’s to mix powders?
1) versatile - able to mix wide range of materials efficiently
2) Scalable—small to large batches.
3) Integrates with upstream/downstream processes to facilitate automation and continuous processing.
4) Small footprint.
5) Cost and energy efficient.
6) In-line monitoring.
7) Environmental controls, e.g. temperature, vacuum.
What is the basic principle of powder mixing operation?
splitting up groups of particles (agglomerates) and rearranging them spatially.
Three mechanisms of mixing:
1) Convective mixing - between large groups of particles
2) Shear Mixing - mixing at an interface between large groups of particles
3) Diffusive mixing - mixing within large groups of particles.
How does a tumbling mixer work?
- uses mainly shear and diffusing mixing mechanisms.
- suitable for free-flowing particles.
- rotation of mixing vessel mixes the powders together
How does a shear mixer work?
- uses high velocity rotating blades to create a high shear force to break up agglomerates.
- uses mainly shear and diffusing mixing mechanisms.
What affects the performance of tumbling mixers?
1) fill volume (shouldn’t exceed 50-60%)
2) residence time
3) rotation speed
4) inclination angle of mixer
What type of material can’t be used in a shear mixer?
Friable material
How does a Nauta mixer work?
- It is a conical screw mixer whose screw rotates axially and orbitally.
- uses convective mixing as uses three types of flow.
Types of flow occurring in a Nauta mixer?
1) Axial - screw brings powder at bottom towards the top
2) Tangential -screw mixes powder particles in a circular motion horizontally.
3) Radial - as the screw brings the powder from the bottom to the top, the powder on top drop to the bottom due to void created.
How does the fluidised bed mixer work?
High velocity air is pumped through the powder bed hence dispersing the powder particles. Gas reach the top of the bed and escape as bubbles.
What type of powders is the fluidised bed mixer suitable for?
medium-density (= 800kgm^2) and friable powders.
How does a static mixer work?
It has no moving parts but mixing occurs as powder flows through the motionless mixing element. It is a continuous process.
List all the types mixer?
1) Tumbling mixer
2) Nauta mixer
3) Shear mixer
4) Fluidised bed mixer
5) Static mixer
5 key practical considerations:
1) ensure mixer matches material properties
2) ensure appropriate fill volume and mixing mechanism
3) determine appropriate mixing time by monitoring mixture at intervals
4) use geometric pre-blending if necessary
5) dissipate statics by earthing the mixer at relative humidity >40%.
