Powders Flashcards
Why do powders disperse and dissolve more readily than compacted dose forms?
They have a greater specific surface area
What are powders?
Intimate mixtures of dry, finely divided drugs and/or chemicals that may be intended for internal (oral) or external (topical) use
What are the advantages of powders?
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
What are the advantages of using powders for reconstitution?
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
Bulk oral powders are typically limited to what types of drugs?
Relatively non-potent drugs (laxatives, antacids, supplements, analgesics, etc. that patient measures on their own)
Best way to store powders?
Wrap in bond/parchment paper, but might get more protection by using cellophane/polyethylene envelopes
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?
Diluent = starch (typically) Container = wide mouth jar, etc. (based on powder property) Labelling = content, concentration of API (% w/w or weight API/gram powder)
In bulk powders for internal application, answer the following questions:
What container is used?
How should they be administered?
How are they labelled?
Container = Based on properties of powder Administration = Tsp./Tbsp. Labelling = Weight API/volume to be ingested
What is comminution?
The process of decreasing particle size to create a uniform size of particles
What are the three methods of comminution and when are they used?
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
What is pulverization by intervention?
1) Dissolve compound in solvent
2) Spread on slab/mix in mortar to evaporate solvent
3) Powder will recrystallize out as fine particles
How does levigation work?
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
What are the most important properties of powders in external and internal dosage forms?
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)
How to determine particle size?
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)
Analytical sieving
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
Powder fineness - classification of powders by analytical sieving
Very coarse (>1000um) Coarse (355-1000um) Moderately fine (180-355um) Fine (125-180um) Very fine (90-125um)
How is sieve analysis done?
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
When is optical microscopy used?
Used for particles > 1um
Especially useful for non-spherical particles
For crystallinity characterization, particles are mounted in mineral oil
What are some components of particle size characterization?
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
What is the Coulter Principle?
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
What is the angle of repose/flow ability of particles?
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
What is the true volume of powder?
Space occupied by powder irrespective of spaces greater than intramolecular space
What is the bulk volume of powder?
Volume occupied by selected weight of powder
What is the apparent density of powder? How can we determine bulk density?
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
What is the true density of powder?
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
Are powders with low apparent density and large bulk volumes considered light or heavy?
Light
What is the tap density of powder?
Volume in cylinder after it has been tapped
Mass/tapped volume
What are the compressibility index and Hausner ratio?
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
What is granular density?
Contributions to particle volume from open pores smaller than some limiting size, depending on unit of measurement
What is mercury porosimetry? What does it apply to?
Limited pore size depends on maximum intrusion pressure - influences granular density
Will granular density always be larger or smaller than true density? Why?
Smaller because there is an additional contribution from pore volume (mercury porosimetry)
What is pycnometric density? What value is it equal to?
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
What are eutectic mixtures?
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)
Geometric dilution
Blend >2 powders in unequal amount
Add equal amount of powder into mortar, then triturate into uniform powder mixture
What are some stability considerations with regard to powders?
Powders may cake into hard masses, develop odours, and change colours
