Mixing and Flowability Flashcards
Mixing in granulation
First step is mixing and mixing is done after milling
Mixing in direct compression
1st step
Purpose of Mixing
Uniformity of dose (quality control), better appearance (acceptability) and modified drug release (liberation)
Perfect Mix Outline
1:1 API to excipient. An ideal not typically obtainable
Random Mix Outline
Most common mix. Fractions of this mix must have the same ratio of API to excipient that the whole system
Positive mixture
Powder mixed by diffusion (no energy added) spontaneously and irreversibly. It’s irreversible as it can’t be separated by drying. Eg miscible liquids and gases
Negative mixture
Mixing requires energy added. Components separate out without constant energy added. Eg suspension and emulasion
Neutral mix
Static behaviour. Doesn’t mix without energy added, unlikely to separate out when energy is removed. Eg solids and semisolids
Scrutiny Scale Outline
Minimum volume/weight of a sample needed to mix to ensure mixing is done properly
How to minimise variation in samples
choose scrutiny scale, choose appropriate particle size and appropriate method of mixing
3 Mechanisms of Mixing
Convective, Shear and Diffusive. All mechanisms occur in most machines to some extent
Convective Mixing Outline
Transfer large groups of molecules from 1 part of powder bed to another
Shear Mixing Outline
Layers of powders moved move over eachother
Diffusive Mixing Outline
Individual particles move between each other through void space
Mixing Considerations
API lower conc then excipients (geometric dilution), volume fill, dosage formulation and mixing mechanism
Geometric Dilution Outline
Add API (lowest quantity in mix) first, add equal amount of excipients and add more excipients slowly
Powder Mixing Equipment
Tumbling mixers/blenders, agitator mixers, high-speed mixers/granulators and fluidised bed mixers
Tumbling mixer Outline
Powder is rotated in drums of different shapes around an axis. Mixing occurs by shear and diffusive. Used in mixing prior to tableting. Blending lubricants, glidants and external disintegrants
Tumbling Mixers Advantages and Disadvantages
Advantages: useful for free-flowing. Disadvantages: doesn’t work for poor flowing powders and causes powder segragation. Relies on properties of flow
2 types of agitator mixers
ribbon and planetary
Ribbon Mixer Outline
Convective mixing by helical blade. Better for poor flow powders.
Planetary Mixer Outline
Convective and diffusive mixing. Mixing blade on rotating arm
Cohesion Def
Attractive forces between particles of the same type
Adhesion Def
Attractive forces between particles of different types
Angles of Response Outline
Angle between powder heap and flat surface. Bigger angle = larger powder pile = worse packing geometry
Forces that define powder volume
gravity, adhesive and cohesive forces. Resultanat volume occurs when these forces reach equilibrium
3 types of powder density
true density, bulk density and tapped density
True Density Def
Material density without including volumes
Bulk Density Def
Mass of powder divided by powder bulk volume. Takes macroscopic interarticular voids in powder
Tapped Density Def
Mass of powder divided by tapped volume. used as estimation of powder flowability and compressability
Realtionship between true desnity and bulk density
If powders of equalt true density have different bulk densities. The 1 with the higher bulk density has a lower chance of compactibility
Realtionship between sample’s powder size range and flowability
wider particle size range = greater cohesion
Factors Effecting Packing Density
Particle size/distribution, particle shape (minimese prosioty and arch/bridge formation), surface properies (reduce friction) and handling/processing
Hopper Outline
Tanks contains bulk powders, powder transfer during processes, poder flows through oraffice at end. Time taken for powcer to flow through is measure of flowability
Free Flowing Powders in Hopper
Mass flow. 1st particles put in are 1st to come out of orafice
Funnel Flow Powders in Hopper
Funnel flow. Lat particles put in are last particles out
Carr’s / Compressability Index Outline
% measure of flow taking into account tapped denity and bulk density. Lower index = better flow = lower tapped density
Hausner ratio
Ratio tapped density/ bulk density. lower Hausner ratio = lower tapped density = better flowability
Flow characyterisation
angle of respose, Carr’s/compressibility index + hauser’s ratio and funnel times
Improving flow
Smaller, smoother , more spherical particles. Reduce charge and surface tension. Add glidants (reduce adhesion and cohesion) and alter manufacturing process (rotating systems)
Types of Powder Segregation
Percolation, Trajectory and Elutiration
Percolation Segmentation Outline
Smaller particles pass through voids between larger molecules. Smaller particles congregate at bottom
Trajectory Segmentation Outline
Larger particles have greater kinetic energy. Larger particles are pushed further out
Elutriation/ Fluidisation Segregation
Flow separates smaller particles towards top
Prevention of powder segragation
particle size reduction, controlled crystallisation, excipients and APIs of same density, granulation (particle size uniformity), reduce vibration and ordered mixing
