Mixing and Flowability

Question 1

Mixing in granulation

Answer 1

First step is mixing and mixing is done after milling

Question 2

Mixing in direct compression

Answer 2

1st step

Question 3

Purpose of Mixing

Answer 3

Uniformity of dose (quality control), better appearance (acceptability) and modified drug release (liberation)

Question 4

Perfect Mix Outline

Answer 4

1:1 API to excipient. An ideal not typically obtainable

Question 5

Random Mix Outline

Answer 5

Most common mix. Fractions of this mix must have the same ratio of API to excipient that the whole system

Question 6

Positive mixture

Answer 6

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

Question 7

Negative mixture

Answer 7

Mixing requires energy added. Components separate out without constant energy added. Eg suspension and emulasion

Question 8

Neutral mix

Answer 8

Static behaviour. Doesn’t mix without energy added, unlikely to separate out when energy is removed. Eg solids and semisolids

Question 9

Scrutiny Scale Outline

Answer 9

Minimum volume/weight of a sample needed to mix to ensure mixing is done properly

Question 10

How to minimise variation in samples

Answer 10

choose scrutiny scale, choose appropriate particle size and appropriate method of mixing

Question 11

3 Mechanisms of Mixing

Answer 11

Convective, Shear and Diffusive. All mechanisms occur in most machines to some extent

Question 12

Convective Mixing Outline

Answer 12

Transfer large groups of molecules from 1 part of powder bed to another

Question 13

Shear Mixing Outline

Answer 13

Layers of powders moved move over eachother

Question 14

Diffusive Mixing Outline

Answer 14

Individual particles move between each other through void space

Question 15

Mixing Considerations

Answer 15

API lower conc then excipients (geometric dilution), volume fill, dosage formulation and mixing mechanism

Question 16

Geometric Dilution Outline

Answer 16

Add API (lowest quantity in mix) first, add equal amount of excipients and add more excipients slowly

Question 17

Powder Mixing Equipment

Answer 17

Tumbling mixers/blenders, agitator mixers, high-speed mixers/granulators and fluidised bed mixers

Question 18

Tumbling mixer Outline

Answer 18

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

Question 19

Tumbling Mixers Advantages and Disadvantages

Answer 19

Advantages: useful for free-flowing. Disadvantages: doesn’t work for poor flowing powders and causes powder segragation. Relies on properties of flow

Question 20

2 types of agitator mixers

Answer 20

ribbon and planetary

Question 21

Ribbon Mixer Outline

Answer 21

Convective mixing by helical blade. Better for poor flow powders.

Question 22

Planetary Mixer Outline

Answer 22

Convective and diffusive mixing. Mixing blade on rotating arm

Question 23

Cohesion Def

Answer 23

Attractive forces between particles of the same type

Question 24

Adhesion Def

Answer 24

Attractive forces between particles of different types

Question 25

Angles of Response Outline

Answer 25

Angle between powder heap and flat surface. Bigger angle = larger powder pile = worse packing geometry

Question 26

Forces that define powder volume

Answer 26

gravity, adhesive and cohesive forces. Resultanat volume occurs when these forces reach equilibrium

Question 27

3 types of powder density

Answer 27

true density, bulk density and tapped density

Question 28

True Density Def

Answer 28

Material density without including volumes

Question 29

Bulk Density Def

Answer 29

Mass of powder divided by powder bulk volume. Takes macroscopic interarticular voids in powder

Question 30

Tapped Density Def

Answer 30

Mass of powder divided by tapped volume. used as estimation of powder flowability and compressability

Question 31

Realtionship between true desnity and bulk density

Answer 31

If powders of equalt true density have different bulk densities. The 1 with the higher bulk density has a lower chance of compactibility

Question 32

Realtionship between sample's powder size range and flowability

Answer 32

wider particle size range = greater cohesion

Question 33

Factors Effecting Packing Density

Answer 33

Particle size/distribution, particle shape (minimese prosioty and arch/bridge formation), surface properies (reduce friction) and handling/processing

Question 34

Hopper Outline

Answer 34

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

Question 35

Free Flowing Powders in Hopper

Answer 35

Mass flow. 1st particles put in are 1st to come out of orafice

Question 36

Funnel Flow Powders in Hopper

Answer 36

Funnel flow. Lat particles put in are last particles out

Question 37

Carr's / Compressability Index Outline

Answer 37

% measure of flow taking into account tapped denity and bulk density. Lower index = better flow = lower tapped density

Question 38

Hausner ratio

Answer 38

Ratio tapped density/ bulk density. lower Hausner ratio = lower tapped density = better flowability

Question 39

Flow characyterisation

Answer 39

angle of respose, Carr's/compressibility index + hauser's ratio and funnel times

Question 40

Improving flow

Answer 40

Smaller, smoother , more spherical particles. Reduce charge and surface tension. Add glidants (reduce adhesion and cohesion) and alter manufacturing process (rotating systems)

Question 41

Types of Powder Segregation

Answer 41

Percolation, Trajectory and Elutiration

Question 42

Percolation Segmentation Outline

Answer 42

Smaller particles pass through voids between larger molecules. Smaller particles congregate at bottom

Question 43

Trajectory Segmentation Outline

Answer 43

Larger particles have greater kinetic energy. Larger particles are pushed further out

Question 44

Elutriation/ Fluidisation Segregation

Answer 44

Flow separates smaller particles towards top

Question 45

Prevention of powder segragation

Answer 45

particle size reduction, controlled crystallisation, excipients and APIs of same density, granulation (particle size uniformity), reduce vibration and ordered mixing