Pharmaceutical powders Flashcards

1
Q

What is the principle of geometric dilution? (What is important when mixing powder with unequal quantities?)

A
  • 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
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2
Q

How does different particle size and different densities affect mixing powder?

A

for diff particle sizes reduce each powder size separately before mixing
for diff densities put lighter powder first then heavier powder on top

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3
Q

What is a powder?

A
  • pool of solid particles
  • particles can have the same composition or be mixture of chemical compositions
  • usually <1000 micrometres
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4
Q

what are the two things powder particles tend to be?

A

1) irregular in shape

2) heterogeneously distributed

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5
Q

What does the equivalent sphere concept allow? However what does it provide?

A
  • 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.

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6
Q

What is a common method to use to determine particle size?

A

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
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7
Q

What is Martin’s diameter and Feret’s diameter? What does Ferets depend on?

A

Martins- length of a line that bisects the particle

Ferets- distance between drawn tangents (depends on particle orientation)

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8
Q

What changes if the particle size or the particle itself changes?

A

orientation diameter and tangent distance changes

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9
Q

What occurs when incident light hits a particle? What is this called?

A

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

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10
Q

Size distribution is based on what?

A
  • no of particles within each class size (number distribution)
  • particles weight within each class size (weight distribution)
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11
Q

What happens to size distribution as variety of particle size is higher?

A

size distribution will become wider

this is obtained by frequency histogram/curve

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12
Q

For normal size distribution what does the curve look like?

A

curve is symmetrical on either side of the line

- mean, median and mode have the same value

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13
Q

What does +ve/-ve skewed size distribution graphs look like? Which has a higher mode and a higher mean

A

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
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14
Q

What will a log-normal distribution look like?

Why do we plot log scale?

A
  • usually is skewed

- plotting on log normalises the size distribution

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15
Q

What is multimodal distribution and what does it look like?

A
  • has two modes
  • two peaks in the graph and two curves
  • % frequency vs particle diameter on graph
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16
Q

What can you get from a cumulative frequency graph?

A
  • you get the median but NOT the mean
  • only get mean if distribution is normal
  • look at particle diameter corresponding to % frequency of 50%
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17
Q

Flowability depends on?

A

Forces that drive flow:

  • gravity
  • particle mass
  • angle of inclination
  • applied mechanical force

Forces that resist flow:

  • adhesion
  • cohesion
  • surface forces
  • electrostatic interactions
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18
Q

when will a powder flow?

A

when the total flow-promoting forces > total drag forces

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19
Q

will a small or large particle have better flow properties with other parameters being equal?

A

a large particle

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20
Q

will have a spherical or irregular particle have better flow properties if all parameters being equal?

A

a spherical particle

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21
Q

For particles with <100um what happens to the adhesion/cohesion and flowability?

A

the adhesion and cohesion will increase

flowability will decrease

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22
Q

will particles with high or low density have better flow properties?

A

a powder with high density particles

- flow-promoting forces act more strongly and increase flow

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23
Q

what is porosity and at what percentage do powders aggregate?

A

porosity is a measure of how tightly/loosely particles are packed

aggregate- >50%
‘real’ powder- 30-50%
polydisperse - <26%

24
Q

will powders with a high or low moisture content have better flow properties?

A

a low moisture content will have

  • too low can backfire as moisture can prevent flow by becoming sticky
25
Q

What packing is the most porous? and which one is the least porous?

A

cubic packing

  • most porous
  • loosest
  • arrangement porosity is around 48%

rhombohedral packing

  • tightest
  • least porous
  • arrangement porosity is around 26%
26
Q

what is the true volume and the true density?

A

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

27
Q

What is the bulk volume and bulk density? How can you calculate the bulk density?

A
  • 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)

28
Q

What are the volume and density properties of ‘light’ and ‘heavy’ powders?

A

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
29
Q

For trouble shooting how can you control shape, control roughness?

A

spray-drying to produce regular shaped particles

30
Q

For trouble shooting how can you increase flow-promoting forces?

A
  • add excipient

- use mechanical assistance

31
Q

What is the Angle of Repose and how do you calculate it?

A

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

32
Q

What is the AoR fior better flow?

A

A Flatter cone means a decrease in AoR and so better flow

  • 25-30 degrees = excellent
  • > 66 degrees = poor
33
Q

Describe the two bulk-density based methods. What are the two volumes you find called?

A
  • 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
34
Q

How do you calculate the bulk density?

A

Pb= M/Vo
M- mass of powder used
Vo- poured volume

35
Q

What are the two formula to calculate powder flowability?

A

Hausner’s Ratio= Pt/Pb

Carr’s index= (Pt-Pb/Pt) x100

36
Q

Before being swallowed what must powders be?

A

must be dispersion or dissolution in water

37
Q

Multidose bulk powders for internal use should be limited to? and how should it be dispensed?

A

non-potent active ingredients

- should be dispensed with 5mL spoon and packaged in a bottle with a wide opening

38
Q

Name the advantages and disadvantages of bulk oral powders

A

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
39
Q

How are topical powders typically packaged?

A

in bottles with sifter tops and so they need excellent flow properties

40
Q

Name the advantages and disadvantages of topical powders?

A

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
41
Q

why are insufflation powders barely used?

A

due to poor patient adherence and lack of convenience

42
Q

Why are oral powders often used for reconstitution?

A
  • dry solid can be stored for long period of time

- packaged in a large bottle

43
Q

why are excipients added to powders?

A

to prevent caking and aid dissolution

44
Q

when a powder is reconstituted what happens to shelf-life?

A

the shelf life will dramatically decrease

45
Q

what occurs after reconstitution of an oral powder?

A

a suspension will form

- drug conc. will vary with amount of solvent added

46
Q

what powders are mostly used for reconstitution?

A

parental powders as they help increase shelf-life and are packaged suitably

47
Q

Name and describe the main steps in production of pharmaceutical powders

A
  1. size reduction
    - breaks up aggregation formed in storage
    - crushes crystalline drugs and excipients into fine powder
  2. mixing
    - direct mixing
    - use doubling methods
48
Q

What are Eutetic mixtures?

A

results from combination of two powder ingredients where mixtures starts as solid but at room temp it liquifies

49
Q

How can you force a eutetic mixture?

A
  • mix and process powders to trigger liquefaction

- absorb the resulting liquid on an inert solid already present

50
Q

How can you prevent a eutetic mixture?

A
  • mix ingredients separately with an inert powder already present
  • use spatula and glass tile
51
Q

What is needed for effervescent powder formulations?

A
  1. source of acid; mix of citric/tartaric acid

2. source of oxygen; NaHCO3 or CaCO3

52
Q

what occurs when effervescent powders are dispersed in water?

A

neutralisation reaction takes place between acidic and basic components
CO2 is formed and released
so powder must be kept away from moisture

53
Q

Where should bulk powders be stored?

A

in cool dry place in tightly closed container

54
Q

How can you keep effervescent , hygroscopic and deliquescent powders’ integrity?

A

effervescent powder; use an anhydrous form
hygroscopic and deliquescent; use of a dessicant or an excipient
an excipient can absorb humidity

55
Q

What are the three special cases of bulk powders for storage?

A
  • 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