Powder Technology: Powder Mixing and Flow

  • Created by: LBCW0502
  • Created on: 11-10-18 12:43
Why is powder mixing important? (1)
Used in PI and food processing, fundamental process in solid/semi-solid particulate dosage forms, factors affect powder mixing efficiency, ensure maximum efficiency optimised throughout all stages of manufacture with clear defined standards during QC
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Why is powder mixing important? (2)
Content/dose uniformity (safety) - uniformity of weight, uniformity dissolution rate, uniform bioavailability
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How is a random mixture obtained?
If 2 different free-flowing powders of approximately the same particle size/density/shape are mixed, particle non-cohesive, mixing time determines quality of random mixture
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What happens when the particle size is reduced too much?
Increased cohesion and particle aggregation, resulting poor mixing and powder flow properties
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What does the separation of powder components depend upon?
Particle size, particle density, particle shape
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Describe features of segregation
The act or process of segregating. Can occur during handling of completed powder mix. Free-flowing powders. Powders not free flowing/high cohesion/adhesion forces are difficult to mix due to agglomeration
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What are the three types of segregation?
Percolation (smaller particles through voids between larger particles). Trajectory (larger particles travel faster and further than smaller particles). Elutriation ('dusting out', small particles blown into air during mixing, settle on larger ones)
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Can density affect separation of powder?
A separation of powder components can occur if the particles exhibit different densities (even if they are the same size) - costly to carry out particle segregation
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Describe strategies to prevent segregation
Specific particle size range (sieving). Particle size reduction (milling). Controlled crystallisation. Mix with excipients of similar density. Increase particle size (granulation), reduce vibrations/movement, reduce power residence time, ordered mix
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What is an ordered mix?
A mixture of particles where sufficiently small (micronised) particles adsorb to the surface of larger carrier particles
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What is ordered unit segregation?
Percolation separation of different sized carrier particles resulting in drug-enriched areas
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What is displacement segregation?
Another particle component competes for same adsorption site on the carrier e.g. addition of Mg-stearate to tablet formulations
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What is saturation segregation?
Insufficient carrier particles
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Why is the powder flow property important?
Dictates quality of product in terms of weight variation and content uniformity. Used to address segregation problems. Failure of product could be due to flow behaviour during manufacturing
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What are the forces which affect powder flow?
Driving forces promote flow and drag forces prevent flow
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What is cohesion?
Occurs between like surfaces such as component particles of a bulk solid
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What is adhesion?
Occurs between two unlike surfaces such as between a particle and a hopper wall
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Cohesion and adhesion both result from what?
Particle-particle/surface interactions, primarily van der Waal's forces. The strength of these forces increases as particle size decreases and varies with humidity
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What are surface forces?
Tensional forces between surface liquid layers and other particles or electrostatic forces resulting from contact/frictional charging
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What is mechanical interlocking?
Occurs as a result from particle properties (shape)
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How does particle size affect powder flow (10, 100, 250 microns)?
<10 microns (very cohesive, resist gravity, flow only as agglomerates). <100 microns (cohesive flow due to larger SA:Vol ratio, greater frictional forces). >250 microns (free flowing)
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How does particle shape affect powder flow?
Spherical particles (free flowing due to minimal amount of interparticle contact areas (reduced drag forces, reduced friction). Non-spherical particles (greater cohesion esp. flakes/dendritic particles with high SA:Vol ratio)
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How do other particle properties affect powder flow?
Density (higher density particles: flow under gravity, low density particles: more cohesive). Humidity (high: greater adsorbed water surface layer, greater surface tensional forces)
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Describe features of total porosity
Void volume = total porosity, bulk volume of powder, true volume of all powder particles
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What are the three ways of measuring porosity?
Mercury intrusion porosimetry, gas adsorption method, Helium Pyknometer
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Describe features of Mercury Intrusion Porosimetry (1)
Evaluates porosity, pore size distribution, pore volume to characterise solid/powder. Pressure applied, mercury fills larger pores first, as pressure increases filling proceeds to smaller pores
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Describe features of Mercury Intrusion Porosimetry (2)
From pressure vs intrusion data, generate volume/size distribution using Washburn equation. Both inter-particle pores and intra-particle pores characterised
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Describe features of the Gas Adsorption Method
BET. Monolayer of adsorbed molecules into pores. Multilayer/capillary condensation, pore volume with 100% saturation
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Describe features of Helium Pycnometer
Inert gas (He) penetrate finest pores. Sealed chamber of known volume (target pressure with displacement gas). Pressure recorded when stabilised. Valve opened to allow gas to expand in reference chamber. Second pressure recorded. Pressure drop ratio
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What are the indirect methods for measuring powder flow?
Angle of repose, shear cell measurements, bulk density measurements
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What are the direct methods for measuring powder flow?
Hopper flow rate, recording flowmeter
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What is the angle of repose?
The steepest angle at which a sloping surface formed of loose material is table
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Describe features of shear cells or powder rheometers
Force and torque measurements are sampled continuously whilst the blade traverses downwards and then upwards through test material. Work performed is calculated from this data (energy profile for each cycle). Shape/magnitude - material flowability
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Describe features of tap density measurements
Graduated cylinder on rotating cam. Tapping motion, specified drop distance, 250 drops/min
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How do you calculate Carr's Index?
Tap density - bulk density / tap density x 100
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How do you calculate the Hausner ratio?
Tap density / bulk density (H < 1.25 good flow, H > 5 poor flow, in between - add glidant if needed)
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Outline the process of flow through hopper
Direct measurement of flow, time taken for known amount of powder to flow through hopper, shutter over outlet and hopper filled, remove shutter, time measured until discharge completed (discharge = mass/time = flow rate)
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Describe features of recording flowmeter
Direct measurement of flow, powder released from hopper onto a balance, mass of powder measured and recorded as a function of time, flow rate/uniformity of flow are determined
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Describe the ways to improve powder flow
Remove fine particles, adsorb fine particles onto larger particles, drying particles reduce cohesiveness, add glidant (flow activators) to improve flow rate, increase particle size through granulation
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Other cards in this set

Card 2

Front

Why is powder mixing important? (2)

Back

Content/dose uniformity (safety) - uniformity of weight, uniformity dissolution rate, uniform bioavailability

Card 3

Front

How is a random mixture obtained?

Back

Preview of the front of card 3

Card 4

Front

What happens when the particle size is reduced too much?

Back

Preview of the front of card 4

Card 5

Front

What does the separation of powder components depend upon?

Back

Preview of the front of card 5
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