Pharmaceutical powders Flashcards
What is the principle of geometric dilution? (What is important when mixing powder with unequal quantities?)
- smallest weigh powder is titrated with an equal bulk of diluting powder
- 1st dilution is mixed with equal amount of diluents
- process goes on until all powder are intimately mixed
How does different particle size and different densities affect mixing powder?
for diff particle sizes reduce each powder size separately before mixing
for diff densities put lighter powder first then heavier powder on top
What is a powder?
- pool of solid particles
- particles can have the same composition or be mixture of chemical compositions
- usually <1000 micrometres
what are the two things powder particles tend to be?
1) irregular in shape
2) heterogeneously distributed
What does the equivalent sphere concept allow? However what does it provide?
- simplified size analysis for powder
- allows powder particles to be reimagined as a hypothetical sphere and using methods to then estimate its size
doesn’t provide true particle size but just an approx.
What is a common method to use to determine particle size?
sieving
- different size sieves are stacked on top of a receiver pan in decreasing order of mesh aperture size
- equivalent sphere diameter obtained Is calling sieving diameter; corresponds to min. aperture size
What is Martin’s diameter and Feret’s diameter? What does Ferets depend on?
Martins- length of a line that bisects the particle
Ferets- distance between drawn tangents (depends on particle orientation)
What changes if the particle size or the particle itself changes?
orientation diameter and tangent distance changes
What occurs when incident light hits a particle? What is this called?
It is
1) reflected; bounces off particle
2) absorbed; absorbed by particle
3) refracted; light changes direction pass through particle
4) diffracted; light changes direction hitting particle edge
light scattering
Size distribution is based on what?
- no of particles within each class size (number distribution)
- particles weight within each class size (weight distribution)
What happens to size distribution as variety of particle size is higher?
size distribution will become wider
this is obtained by frequency histogram/curve
For normal size distribution what does the curve look like?
curve is symmetrical on either side of the line
- mean, median and mode have the same value
What does +ve/-ve skewed size distribution graphs look like? Which has a higher mode and a higher mean
Positively skewed graphs go to the right and curve off to the right
Negatively skewed graphs shift to the left and curve off to the left
\+ve= mean> mode -ve= mode> mean
What will a log-normal distribution look like?
Why do we plot log scale?
- usually is skewed
- plotting on log normalises the size distribution
What is multimodal distribution and what does it look like?
- has two modes
- two peaks in the graph and two curves
- % frequency vs particle diameter on graph
What can you get from a cumulative frequency graph?
- you get the median but NOT the mean
- only get mean if distribution is normal
- look at particle diameter corresponding to % frequency of 50%
Flowability depends on?
Forces that drive flow:
- gravity
- particle mass
- angle of inclination
- applied mechanical force
Forces that resist flow:
- adhesion
- cohesion
- surface forces
- electrostatic interactions
when will a powder flow?
when the total flow-promoting forces > total drag forces
will a small or large particle have better flow properties with other parameters being equal?
a large particle
will have a spherical or irregular particle have better flow properties if all parameters being equal?
a spherical particle
For particles with <100um what happens to the adhesion/cohesion and flowability?
the adhesion and cohesion will increase
flowability will decrease
will particles with high or low density have better flow properties?
a powder with high density particles
- flow-promoting forces act more strongly and increase flow
what is porosity and at what percentage do powders aggregate?
porosity is a measure of how tightly/loosely particles are packed
aggregate- >50%
‘real’ powder- 30-50%
polydisperse - <26%
will powders with a high or low moisture content have better flow properties?
a low moisture content will have
- too low can backfire as moisture can prevent flow by becoming sticky
What packing is the most porous? and which one is the least porous?
cubic packing
- most porous
- loosest
- arrangement porosity is around 48%
rhombohedral packing
- tightest
- least porous
- arrangement porosity is around 26%
what is the true volume and the true density?
a single solid particle occupies a volume which can be used to calculate its density which is the true volume and that density is the true density
What is the bulk volume and bulk density? How can you calculate the bulk density?
- consider a powder bed
- it occupies a volume which can be used to calculate its density
- that vol is bulk volume and that density is bulk density
bulk volume= total of true volumes (volume of single powder particle) + total of void volumes (interarticular and intraparticular pores)
Pb (g/cm3) = m(g)/ V(cm3)
What are the volume and density properties of ‘light’ and ‘heavy’ powders?
Light powders
- large bulk volume
- low bulk density
- loose packing
- flows better
heavy powders
- small bulk volume
- high bulk density
- tight packing
- cant fully prevent flow
For trouble shooting how can you control shape, control roughness?
spray-drying to produce regular shaped particles
For trouble shooting how can you increase flow-promoting forces?
- add excipient
- use mechanical assistance
What is the Angle of Repose and how do you calculate it?
tan (alpha) = h/r
h- height of powder cone
r- radius of the base of powder cone
AoR is determined after leaving a powder to flow and a cone forms on flat surface
What is the AoR fior better flow?
A Flatter cone means a decrease in AoR and so better flow
- 25-30 degrees = excellent
- > 66 degrees = poor
Describe the two bulk-density based methods. What are the two volumes you find called?
- known amount of powder under test is poured into a measuring cylinder and bulk vol. is measured ; poured volume
- cylinder is placed on a mechanical tapping device and consolidated powder vol. is measured after a certain no. of taps ; tapped volume
How do you calculate the bulk density?
Pb= M/Vo
M- mass of powder used
Vo- poured volume
What are the two formula to calculate powder flowability?
Hausner’s Ratio= Pt/Pb
Carr’s index= (Pt-Pb/Pt) x100
Before being swallowed what must powders be?
must be dispersion or dissolution in water
Multidose bulk powders for internal use should be limited to? and how should it be dispensed?
non-potent active ingredients
- should be dispensed with 5mL spoon and packaged in a bottle with a wide opening
Name the advantages and disadvantages of bulk oral powders
Advantages
- increase in stability and shelf life
- allows large dose admin.
- fast absorption
Disadvantages
- bulky packaging
- drug degradation still possible
- must consider organoleptic properties
- limited to admin of non-potent drug
How are topical powders typically packaged?
in bottles with sifter tops and so they need excellent flow properties
Name the advantages and disadvantages of topical powders?
Advantages
- easy use
- friction reduced
- absorption of skin moisture
Disadvantages
- risk of blocking pore
- irritation possible
- inhalation risk
- cant use on broken skin
- potential contamination issues
why are insufflation powders barely used?
due to poor patient adherence and lack of convenience
Why are oral powders often used for reconstitution?
- dry solid can be stored for long period of time
- packaged in a large bottle
why are excipients added to powders?
to prevent caking and aid dissolution
when a powder is reconstituted what happens to shelf-life?
the shelf life will dramatically decrease
what occurs after reconstitution of an oral powder?
a suspension will form
- drug conc. will vary with amount of solvent added
what powders are mostly used for reconstitution?
parental powders as they help increase shelf-life and are packaged suitably
Name and describe the main steps in production of pharmaceutical powders
- size reduction
- breaks up aggregation formed in storage
- crushes crystalline drugs and excipients into fine powder - mixing
- direct mixing
- use doubling methods
What are Eutetic mixtures?
results from combination of two powder ingredients where mixtures starts as solid but at room temp it liquifies
How can you force a eutetic mixture?
- mix and process powders to trigger liquefaction
- absorb the resulting liquid on an inert solid already present
How can you prevent a eutetic mixture?
- mix ingredients separately with an inert powder already present
- use spatula and glass tile
What is needed for effervescent powder formulations?
- source of acid; mix of citric/tartaric acid
2. source of oxygen; NaHCO3 or CaCO3
what occurs when effervescent powders are dispersed in water?
neutralisation reaction takes place between acidic and basic components
CO2 is formed and released
so powder must be kept away from moisture
Where should bulk powders be stored?
in cool dry place in tightly closed container
How can you keep effervescent , hygroscopic and deliquescent powders’ integrity?
effervescent powder; use an anhydrous form
hygroscopic and deliquescent; use of a dessicant or an excipient
an excipient can absorb humidity
What are the three special cases of bulk powders for storage?
- Hygroscopic powders
powders that absorb moisture from environment - Deliquescent powders
liquify after moisture absorption - Effervescent powders
release moisture into environment ; contain crystallisation water to release when exposed to low-humidity environments or during handling
