Powders & Granules

Question 1

List differences between crystalline and amorphous solids.

Answer 1

Crystalline
- Have an orderly arrangement of the lattice units
– Have higher purity
– Are more physically and chemically stable
– Have LOWER solubility
– Have a NARROW melting point range
– Are LESS compressible
– Have BETTER FLOW
– Are LESS hygroscopic

Amorphous solids:
– have no order of arrangement
– are less physically and chemically stable (due to the weakness of the interaction
between molecules)
– Have glass transition (Tg) temperature (and not a narrow melting point)
– Are usually more soluble

Question 2

Define enantiotropic polymorphism

Answer 2

More stable form exists and it is a reversible transformation

Question 3

In polymorphic forms why do we use a metastable form with lower melting point?

Answer 3

Lower melting point = weak lattice = more soluble = faster dissolution rate

Question 4

Which are more soluble: anhydrous crystals or hydrate crystals.

Answer 4

Anhydrous crystals

Question 5

Which powder properties can particle size affect?

Answer 5

• Flow
• Powder packing and compaction
• dissolution rate
• Sedimentation

Question 6

What are advantages of having an amorphous dispersion?

Answer 6

• In amorphous dispersions, the amorphous drug is stabilized by a presence of a polymer.
• The polymer helps to stabilize the drug in the solid state and prevents the drug crystallization on
  dissolution.
• This results in increased solubility of the amorphous material and increased physical
  stability.
• Itraconazole is practically insoluble in water, and by making an amorphous dispersion
  with HPMC, its solubility was increased, and its bioavailability was increased by 30%.

Question 7

Define micromeritics

Answer 7

The science and technology of small particles
- particle size measurements
- size distribution
- packing arrangements

Question 8

What are importance of particle size?

Answer 8

• Affect flow and packing properties
• Facilitate drying
• Improve penetration in lungs

Question 9

Which type of density will have the highest inter particulate spaces?

Answer 9

bulk density

Question 10

Which densities are related to the porosity of powder particles

Answer 10

Bulk density and true density

Question 11

Which particle size has the biggest mesh opening size and smallest mesh size number?

Answer 11

Coarse

Question 12

Explain the methods for determining particle size distribution
1. Microscopy

Optical microscope
Scanning electron microscope
Transmission electron microscopy
Dynamic image analyses

Answer 12

Optical microscope
- powder dispersed on microscope slide

Scanning electron microscope
- powder are fixed to aluminum stubs

Transmission electron microscopy
- powder is set in resins

Dynamic image analyses
- automated image analyses for light and electron microscopy

Question 13

which particle size has the most mesh size number

Answer 13

very fine

Question 14

Explain the methods for determining particle size distribution
Sieving method

Answer 14

Predetermined weight of dry powder is passed through wire mesh screens, having openings of different sizes and the weight of powder that is retained on each sieve is measured

Question 15

What does a LARGE sieve # (mesh) indicate for sieve opening

Answer 15

Small sieve opening (small particle size)

Question 16

Advantages and Disadvantages of Sieving method

Answer 16

Advantages
- Technique is well adapted for bulk materials

Disadvantages
- Smallest practical sieve size 400 mesh is 38um
- amount of energy is empirically determined

Question 17

Sedimentation Method

Answer 17

Settling of a single particle in a liquid medium under the influence gravitational and centrifugal forces

Question 18

Explain crack propagation

Answer 18

Material breaks along cracks, so most effective size reduction would be to focus force on cracks

Question 19

Explain the bulk powder properties (including, excluding)

True density
True volume
Void/%porosity
Particle density
Bulk density
Tapped density

Answer 19

True density
- ratio of mass of particle to its actual volume
- (excludes pores and gaps)

True volume
- weight over true density

Void/%porosity
- bulk volume - true volume over bulk volume

Particle density
- Ratio of mass to volume of particle
- including intraparticule air volume (pores), excluding gaps

Bulk density
- Ratio of bed mass to volume of loose powder bed
- includes pore and gap volumes

Tapped density
- ratio of powder bed mass to volume trapped (or compacted)
- includes pore and gap volumes

Question 20

Explain Void types of air volume
Pores
Gaps

Answer 20

Pores: intRAparticule air volume

Gaps: intERparticule air volume

Question 21

What do light/heavy powders indicate in terms of bulk density and bulk volume

Answer 21

Light
- low bulk density and large bulk volume

Heavy
- high bulk density and small bulk volume

Question 22

What are factors affecting powder flow?

Answer 22

• Adhesion/Cohesion
• Size, shape, density

Question 23

Differentiate between adhesion vs. cohesion

Answer 23

Adhesion: tendency of DISSIMILAR particles to cling one another

Cohesion: tendency of SIMILAR particles to cling one another

Question 24

What particle size flow better?

Answer 24

Bigger particle size flow better (250 um +)

Question 25

Explain the Angle of repose

Answer 25

angle between the free surface of the powder and horizontal plane when poured from a funnel
- reproducibility is poor

Question 26

What does an angle of repose of 25-30 indicate?

Answer 26

Excellent flow = small angle

Question 27

What is an ordered mixture?

Answer 27

• When micronized powders are absorbed on the surface of a larger carrier particle.
• thus minimizing segregation and maintaining good powder flow

Question 28

Explain the 3 mechanisms of powder mixing
Diffusion
Convection
Shear

Answer 28

Diffusion: when powder bed is forced to move/flow, it dilates, i.e increase in air space between particles

Convection: Transfer of large groups of particle from one part of the powder bed to another

Shear: layer of material flows over another layer

Question 29

What are the factors affecting segregation? main one is particle size (3)

Answer 29

1. Percolation
   - small particles fall into spaces between larger particles, small goes to bottom
2. Trajectory
   - larger particles move greater distances then smaller particles
3. Elutriation
   - during mixing “dust” is blown upwards, when mixing stops, dust sediments on top of coarser particles

Question 30

Where do denser particles move? up/down

Answer 30

down

Question 31

Are spherical particles easy/hard to mix?
Effect of segregation?

Answer 31

easy
increase segregation

Question 32

How to minimize segregation?

Answer 32

• Select a similar particle size range for drugs and excipients
• Control crystallization of drugs and excipients to give same particle shape
• Choose excipients with same density as APIs
• Granulation of powder mix
• Reduce vibration after mixing
• Production of an “ordered mix”

Question 33

What are Advantages and disadvantages of powders/granules as a dosage form

Answer 33

Advantages
- more stable than liquids
- can dispense larger doses
- Faster dissolution and absorption rates

Disadvantages
- hard to mask unpleasant tastes
- Not suitable for potent drug with a low dose
- Not suitable for drugs that are inactivated or cause damage to stomach