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Flashcards in Preformulation considerations Deck (59):
1

Capsules are cheaper to manufacture than tablets. True or false?

False - tablets are cheaper

2

What is preformulation?

It is the process before formulating a drug where a drug candidate is turned into a drug product and the physio-chemical properties are determined

3

During preformulation - large amounts of sample are required for analysis to be undertaken. True or false?

False - small amounts of sample required

4

How can the molecular or intrinsic properties of the inherent drug be modified?

Can only be changed by modifying the structure

5

What are the molecular properties that can be modified by changing the chemical structure of the drug?

Stability to oxidation, hydrolysis
Solubility
Hygroscopicity
pKa
Partition coefficient

6

Macroscopic/bulk properties can't be changed. True or false?

False - can be changed and change based on other excipients present

7

For the final drug to be given orally as a solid form, what solubility is preferred?

10mg/ml

8

What is hygroscopicity?

The tendency of a substance to attract water from its immediate environment by absorption or adsorption

9

Does water selectively bind to polar or non-polar regions of a solid surface?

Polar - so the extent of absorption is related to the degree of polarity

10

Adsorption of water onto most crystalline solids causes the solid to dissolve. True or false?

False - does not cause it to dissolve

11

Why doesn't adsorption of water onto crystalline solids cause the solid to dissolve?

Because only a few layers of water molecules adsorb onto the surface so the volume isn't sufficient enough to allow dissolution

12

Salts have a greater tendency to absorb water than free acid or base. True or false?

True

13

How is water uptake usually determined?

Measuring an uptake in mass -
thermogravimetric analysis (TGA)
dynamic vapour sorption (DVS)

14

What is the enthalpy of fusion?

The change in enthalpy resulting from heating a given quantity of a substance to change its state from solid to liquid

15

Melting point doesn't give any information about the purity of a drug. True or false?

False

16

What technique is used to measure melting point and enthalpy of fusion?

differential scanning calorimetry

17

Particle size and surface area do not affect dissolution rates. True or false?

False

18

A scanning electron microscope is used to determine particle size and shape. True or false?

False - a light microscope is used

19

It's easy to determine particle size when the particle is spherical. True or false?

True

20

Particles with a diameter of 50 or less have good flow properties. True or false?

False - poor flow

21

Why is it important for powders to have good flow properties?

To ensure blend uniformity and optimal filling of tablet presses or capsule filling machines

22

In preformulation testing, which two measures are used to determine powder flow?

Carr index
Angle of repose

23

The higher the angle of repose, the better the powder flow. True or false?

False - a high angle of repose is bad, and a low angle of repose is good

24

Powders with an angle of repose higher than ___ degrees have unsatisfactory flow properties.

45

25

Powders with an angle of repose close to ___ degrees have excellent powder flow properties

25

26

What are bulk density and tapped density used to measure?

compaction or compressibility (Carr index)

27

How is bulk density measured?

Adding a known mass of powder to a graduated cylinder. The density is calculated as mass/volume

28

How is tapped density measured?

Mechanically tapping the graduated cylinder to see whether further volume change is observed

29

Which is better for manufacturing, a powder that is compressible or non-compressible?

Non-compressible (i.e. low Carr index, higher bulk density)

30

Compaction is the result of ______ and ________

compression
cohesion

31

Compaction of drug powders is usually good. True or false?

False - usually poor so excipients are added which have good compaction properties

32

As amorphous materials have no lattice energy, they are unstable and overtime they will convert to a crystalline form. True or false?

True

33

Amorphous materials exhibit worse solubility and slower dissolution rates than crystalline equivalents. True or false?

False - better solubility and faster dissolution rates

34

Converting a poorly soluble compound into an amorphous material will improve its bioavailability. True or false?

True

35

What is meant by polymorphism?

When a compound exists in at least two different molecular arrangements in the solid state

36

The most stable polymorph has the highest melting point. True or false?

True

37

The most stable polymorph exists in a thermodynamic position of equilibrium and all other forms won't convert to it overtime. True or false?

False - they will convert to it

38

What is the use of X-ray powder diffraction in pre-formulation?

Provides structural data to identify polymorphisms

39

Differential scanning calorimetry differentiates polymorphs based on what?

Their melting points and enthalpies of fusion

40

All polymorphs have the same physiochemical properties. True or false?

False - they have different physiochemical properties

41

The most stable polymorph always has the best bioavailability. True or false?

False - may have the worst processing ability or bioavailability

42

Why will an anhydrous polymorph of a drug dissolve more quickly than a trihydrous form?

Because the anhydrous is not associated with water so dissolves more quickly but as the trihydrous is already associated with water, there is less of an energy change and so will have a slower dissolution rate

43

Amorphous compounds have a higher solubility than crystalline compounds. True or false?

True

44

Which factors determine which API is chosen for formulation and in which dosage form?

Solubility
Salt formation
Rheology
Wettability

45

How is solubility analysed in pre-formulation?

rotating or disc methods are used
the drug is packed into a non-disintegrating disc
only one face of the disc is exposed to the dissolution medium
disc is either held in place or rotated
samples of dissolution medium are taken at given times
SA remains constant
Under these conditions, the amount of drug dissolved per unit time and unit surface area can be determined - providing the intrinsic dissolution rate

46

Esterification of a drug will increase its solubility. True or false?

False - reduce solubility as it is non-polar

47

Degree of ionisation for most polar compounds is not linked to solubility. True or false?

False

48

A large Ka (small pKa) implies a high or low solubility?

High

49

If the pKa is low i.e. less than 5 the salt is unlikely to be stable at physiological pH. True or false?

True

50

What is wettability?

It describes the ability of a liquid to maintain contact with a solid surface. It is defined by measuring the contact angle of a drop of fluid on its surface

51

Strong cohesive forces within the liquid allow for good wettability. True or false?

False - poor wettability

52

Strong adhesive forces between a liquid and solid are good for wettability. True or false?

True

53

What does a contact angle of less than 90 degrees show in terms of wettability?

wetting is very favourable

54

What can be used to increase wettability?

Surfactants

55

What is rheology?

The study of flow matter

56

Most pharmaceutical fluids are Newtonian. True or false?

False, non-newtonian

57

What is meant by plastic flow?

The material does not flow until a certain level of pressure is applied - plastic flow is exhibited by concentrated suspensions

58

What is meant by pseudoplastic flow?

The material flows as soon as pressure is applied and flow increases with increasing pressure

59

What happens in dilatant flow?

When no shear stress is applied, particles are closely packed together
When shear stress is applied, particles become displaced and form clumps
Resistance to flow rises and viscosity increases
Behaviour is reversible with removal of stress
Dilatant flow can be a problem during granulation of tablets