Powders

Question 1

Why do powders disperse and dissolve more readily than compacted dose forms?

Answer 1

They have a greater specific surface area

Question 2

What are powders?

Answer 2

Intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended for internal (oral) or external (topical) use

Question 3

What are the advantages of powders?

Answer 3

Can be blended with fillers to form tablets, capsules, suspensions, semisolids
Can measure exact quantities, ideal for potent drugs
Primary ingredient for most drug delivery systems

Question 4

What are the advantages of using powders for reconstitution?

Answer 4

The stability problems that are often encountered with liquid dosage forms are avoided in powders (can mix powders with applesauce, beverages)
They will need a specific BUD after being constituted, likely need to be stored in fridge

Question 5

Bulk oral powders are typically limited to what types of drugs?

Answer 5

Relatively non-potent drugs (laxatives, antacids, supplements, analgesics, etc. that patient measures on their own)

Question 6

Best way to store powders?

Answer 6

Wrap in bond/parchment paper, but might get more protection by using cellophane/polyethylene envelopes

Question 7

In bulk powders for external application, answer the following questions:
What is the typical diluent?
What container should be used?
How should they be labelled?

Answer 7

Diluent = starch (typically)
Container = wide mouth jar, etc. (based on powder property)
Labelling = content, concentration of API (% w/w or weight API/gram powder)

Question 8

In bulk powders for internal application, answer the following questions:
What container is used?
How should they be administered?
How are they labelled?

Answer 8

Container = Based on properties of powder
Administration = Tsp./Tbsp.
Labelling = Weight API/volume to be ingested

Question 9

What is comminution?

Answer 9

The process of decreasing particle size to create a uniform size of particles

Question 10

What are the three methods of comminution and when are they used?

Answer 10

1) Trituration (for hard, fracturable powders)
2) Pulverization by intervention (for hard crystalline powders that don’t triturate easily or for gummy-type substances)
3) Levigation

Question 11

What is pulverization by intervention?

Answer 11

1) Dissolve compound in solvent
2) Spread on slab/mix in mortar to evaporate solvent
3) Powder will recrystallize out as fine particles

Question 12

How does levigation work?

Answer 12

Small amount of liquid in which compound is not soluble is mixed on slab/in mortar and pestle along with a viscous solvent, like glycerin or mineral oil

Question 13

What are the most important properties of powders in external and internal dosage forms?

Answer 13

Powders should always be finely and uniformly divided (if particles are different sizes, they may stratify upon standing, resulting in an inaccurate dose)
Topical: Smooth to the touch, non-irritating
External: Small particle size = increased surface area = increased rate of dissolution = increased bioavailability (Noyes-Whitney Equation)

Question 14

How to determine particle size?

Answer 14

Sieve analysis, microscopy (with a grid background - Martin’s, Feret’s, projected area diameter), sedimentation rate (Andreasen apparatus), laser light scattering, Coulter counter (particle volume measurements, cascade impactor)

Question 15

Analytical sieving

Answer 15

Sieve sorts particles by width/breadth
Use mechanical sieving when particles are >75um
Must use at least 25g
Agitation methods - mechanical agitation
Endpoint determination (weight of any test sieve does not change by >5% of 0.1g of previous weight

Question 16

Powder fineness - classification of powders by analytical sieving

Answer 16

Very coarse (>1000um)
Coarse (355-1000um)
Moderately fine (180-355um)
Fine (125-180um)
Very fine (90-125um)

Question 17

How is sieve analysis done?

Answer 17

Stack of sieves is arranged in order, powder is put in and shaken
Powder on each sieve is weighed
Percent retained in each sieve is calculated

Question 18

When is optical microscopy used?

Answer 18

Used for particles > 1um
Especially useful for non-spherical particles
For crystallinity characterization, particles are mounted in mineral oil

Question 19

What are some components of particle size characterization?

Answer 19

For spherical particles, size is defined by diameter
For irregular shaped particles, size is defined by a number of describing factors: Feret’s diameter, Martin’s diameter, projected area diameter

Question 20

What is the Coulter Principle?

Answer 20

A “reference method” for particle size analysis
Limit test for particulate matter in large volumes, parenteral solutions
Based on measurable changes in electrical resistance produced by non-conductive particles suspended in electrolytes
Suspended particles pass through a sensing zone and displace a volume of electrolyte
Volume displaced is measured as voltage pulse, height of each pulse is proportional to volume of particle (very accurate)
Measurements are independent of shape, colour, density

Question 21

What is the angle of repose/flow ability of particles?

Answer 21

Particles flow differently and will create a different angle of repose
Need to be aware of how particles flow and how this influences homogenicity of powders
Lower angles of repose indicate better flow property
Angle of 25-30 is an excellent flow property, angle of >65 is a very poor flow property

Question 22

What is the true volume of powder?

Answer 22

Space occupied by powder irrespective of spaces greater than intramolecular space

Question 23

What is the bulk volume of powder?

Answer 23

Volume occupied by selected weight of powder

Question 24

What is the apparent density of powder? How can we determine bulk density?

Answer 24

Weight of sample/Bulk volume
Measure the volume of a known mass of powder that has been passed through a screen into a graduated cylinder or through a measuring apparatus into a cup

Question 25

What is the true density of powder?

Answer 25

Weight of sample/true volume
The average mass per unit volume, exclusive of all voids that are not a fundamental part of molecular packaging arrangement

Question 26

Are powders with low apparent density and large bulk volumes considered light or heavy?

Answer 26

Light

Question 27

What is the tap density of powder?

Answer 27

Volume in cylinder after it has been tapped

Mass/tapped volume

Question 28

What are the compressibility index and Hausner ratio?

Answer 28

Compressibility index = (100 (bulk volume - tapped volume)) / bulk volume
Hausner ratio = Bulk volume/tapped volume
Both are measures of propensity (tendency) of a powder to be compressed
Free-flowing powders will have less powder interactions, therefore bulk and tapped density will be close in value

Question 29

What is granular density?

Answer 29

Contributions to particle volume from open pores smaller than some limiting size, depending on unit of measurement

Question 30

What is mercury porosimetry? What does it apply to?

Answer 30

Limited pore size depends on maximum intrusion pressure - influences granular density

Question 31

Will granular density always be larger or smaller than true density? Why?

Answer 31

Smaller because there is an additional contribution from pore volume (mercury porosimetry)

Question 32

What is pycnometric density? What value is it equal to?

Answer 32

Density measured by gas pycnometry. Determine volume of known mass powder by measuring volume displaced by powder - quotient of mass and volume and it pycnometric density
Should be equal to true density

Question 33

What are eutectic mixtures?

Answer 33

Mixtures of two compounds that usually do not interact to form new chemical compounds but at certain ratios, inhibit crystallization of one another, resulting in a lower MP in system than either component (e.g., aspirin and acetaminophen)

Question 34

Geometric dilution

Answer 34

Blend >2 powders in unequal amount

Add equal amount of powder into mortar, then triturate into uniform powder mixture

Question 35

What are some stability considerations with regard to powders?

Answer 35

Powders may cake into hard masses, develop odours, and change colours