WEEK 1: Solid Dosage Forms

Question 1

Pharmaceutical companies give a single number for an average sized particle of a particular drug. If drug particles are organic in shape, how is this determined?

Answer 1

This is done using the “equivalent sphere” method, which involves the assumption that every particle can be approximated to a sphere, and this can be characterised by a diameter.

Question 2

Match the four approaches for measuring diameter with their definitions:

a. Projected perimeter diameter
b. Projected area diameter
c. Feret’s diameter
d. Martin’s diameter

1. Diameter of a circle having the same area
2. Distance between widest points
3. Diameter of a circle having the same perimeter
4. Length of line dissecting the particle

Answer 2

a3, b1, c2, d4

Question 3

What are some limitations to measuring particles size using sieving

Answer 3

• each sieve collects a range of particle sizes
• results are time-dependent
• electrostatic forces increase as particle size reduces, and particles that are less than 40 µm can be quite difficult to separate and so behave as larger particles
• sieving can cause fragile particles to break, changing their particle size

Question 4

A course powder is greater than …µm

Answer 4

> 355 µm

Question 5

A moderately fine powder ranges between … and …µm

Answer 5

180 - 355 µm

Question 6

A fine powder ranges between … and …µm

Answer 6

125 - 180 µm

Question 7

A very fine powder is less than …µm

Answer 7

< 125 µm

Question 8

A micronised / ultrafine powder is less than …µm

Answer 8

< 10 µm (most < 5 µm)

Question 9

What is Stokes diameter?

Answer 9

A method that measures particle size using sedimentation. particles must be suspended in a liquid. The speed at which the particles settle is the diameter of the equivalent sphere having the same settling velocity.

Question 10

(Regarding Strokes diameter)
For … particles it would take too long to wait for settling with gravity, so a … is used to increase the speed of sedimentation.

Answer 10

small
centrifuge

Question 11

What are the limitations to measuring particles using Strokes diameter?

Answer 11

• There’s a limited particle size range that can be used because Brownian motion causes problems below 1µm
• Above 50µm settling can be turbulent.
• It can’t be used for particles that aren’t close to be spherical because irregular shapes sediment more slowly.
• It can’t be used for mixtures of powders that have different densities.

Question 12

Match the method of particle measurement with what it measures:

a. Coulter counter
b. Strokes diameter
c. Laser light scattering

1. particle size
2. projected area diameter and sometimes volume diameter
3. volume diameter

Answer 12

a3, b1, c2

Question 13

In order to measure volume diameter through the Coulter counter test particles must be capable of being suspended in an … solution.

Answer 13

electrolyte

Question 14

A Coulter counter measures the …. crossing through an aperture, and then when a … comes along it displaces a volume of electrolyte solution and this changes the electrical current. The machine converts this signal into a … volume.

Answer 14

electrical current
particle
displacement

Question 15

Match the method of particle measurement with the size of particles it can measure:

a. Coulter counter
b. Strokes diameter
c. Laser light scattering

1. > 0.2µm
2. > 0.1 µm
3. 50µm - 1µm

Answer 15

a1, b3. c2

Question 16

When using laser light scattering to measure a particles size, the size is estimated by the … and … of …

Answer 16

intensity and angle of diffraction.

Question 17

T or F
(Regarding laser light scattering)
A smaller particle will have a small angle diffraction whilst a larger particle will have a comparatively large angle of diffraction.

Answer 17

F
vice versa

Question 18

…. is a type of laser light scattering that can be used for particles that are smaller than around 100 nm, which are termed ‘colloidal’ in size.

Answer 18

Dynamic light scattering (DLS)

Question 19

Which of the following techniques provide the volume diameter of an equivalent sphere?

Question 20

T or F
When we talk about particles of a powder, we are taking about only one type of molecule, e.g. an API such as paracetamol or an excipient such as starch.

Answer 20

T

Question 21

T or F
Granules can only be made up of particles of the same molecule

Answer 21

F

Question 22

List some characteristics that are affected by particle size and shape.

Answer 22

dissolution rate
sedimentation rate
powder flow and mixing
compressibility

Question 23

Which of the arithmetic means require the number of particles to be known?

Answer 23

Number mean diameter and Surface-number mean diameter

Question 24

T or F
Intra-particulate voids are as important to consider as inter-particulate voids.

Answer 24

T

Question 25

If a particle is said to be porous this means it has...

Answer 25

intra-particulate voids.

Question 26

T or F All particles have inter-particulate voids

Answer 26

T

Question 27

T or F A single material can have numerous true densities

Answer 27

F Only 1

Question 28

True density of a non-porous material is measured by ...

Answer 28

liquid displacement.

Question 29

When it comes to porous materials, .... is used to measure true density.

Answer 29

gas displacement

Question 30

When the intra-particulate voids are included with the particle in the measurement of density, then we are measuring what is known as ... density.

Answer 30

granule

Question 31

Granule density is measured by ... displacement.

Answer 31

mercury

Question 32

Why is mercury used to measure granule density?

Answer 32

Mercury fills inter-particulate voids but cannot enter intra-particulate voids.

Question 33

The density of a whole powder, including all of the void spaces, is known as the ... density.

Answer 33

bulk

Question 34

T or F Tapped density using 500 taps will mean that the powder takes up a smaller volume than the 3-tap method, and so therefore the density value is smaller

Answer 34

F The density value will be larger

Question 35

T or F Powders with low bulk density take up more space than powders with a higher bulk density

Answer 35

T

Question 36

T or F True density is always a larger number than bulk density

Answer 36

T

Question 37

T or F A bulk density value of 0.6 g/mL means that 1 g of powder will take up 0.6 mL in volume

Answer 37

F

Question 38

What are the two main influences of total porosity?

Answer 38

particle size and shape, because these affect the way that particles pack together.

Question 39

T or F Total porosity can be altered by manipulating inter-particulate porosity.

Answer 39

T