Powders for Pharmaceutical Use (1/3)

Question 1

Define: Excipient

Answer 1

Non-active ingredients, give functionality to the dosage form

Question 2

What are pharmaceutical powders?

Answer 2

Intimate mixtures of dry, finely divided API and excipients for use internally (oral, sachet) or externally (topical, dusting powder)

Question 3

What are pre-formulation and formulation studies used to test for?

Answer 3

Detect and identify any impurities and degradation products
Done via qualitative and quantitative analysis (NMR, chromatography)
BP specification will include acceptable limits on any impurities

Question 4

What about the API is found out during pre-formulation?

Answer 4

How it behaves

How it interacts with excipients

Question 5

What is involved in accelerated stability testing?

Answer 5

USe of high temperatures and high humidity

Question 6

Why is it important to understand an APIs chemical stability?

Answer 6

Temperature - affects sterilisation method
pH - body fluids e.g. stomach
Moisture - which packaging to use
Oxygen - how to manufacture
Light - storage, packaging

Question 7

How can the solubility of an API be altered?

Answer 7

By adding different salt forms e.g. HCl

Question 8

Which 2 forms can solid APIs be in?

Answer 8

Crystalline or amorphous (no regular lattice arrangement)

Question 9

Define: Polymorph

Answer 9

The different forms of a crystalline APIs which also have different crystal packing arrangements to each other
These different crystal forms have different physiochemical and mechanical properties

Question 10

Which forms of polymorph are referred to as ‘metastable’?

Answer 10

Forms that are less stable than the most stable polymorph

Question 11

What is the purpose of ‘polymorph screens’?

Answer 11

Strategy to discover the most stable polymorphs - involve lots of re-crystallisations under different conditions (different solvents)

Question 12

Which 3 things does polymorphism impact upon?

Answer 12

Solubility (most stable polymorph is the least soluble)
Dissolution rate (proportional to its solubility)
Patent protection

Question 13

How are dissolution rates and bioavailability linked?

Answer 13

Greater dissolution increases bioavailability and vice versa

Question 14

Define: Hygroscopicity

Answer 14

The degree of moisture uptake by an API and its consequences

Water is adsorbed on surface and can then diffuse into bulk

Question 15

Which 3 consequences does adsorption of moisture onto API surface (hygroscopicity) have?

Answer 15

Can:
Cause physical changes e.g. swelling
Cause chemical changes e.g. degradation
Have bacterial effects e.g. microbial spoilage

Question 16

List 4 factors which affect processing

Answer 16

Particle size and shape
Bulk density
Powder flow
Compressibility

Question 17

What is the Noyes-Whitney equation?

Answer 17

Equation

Question 18

Define the terms in the Noyes-Whitney equation

Answer 18

dm/dt = rate of mass transfer (dissolution rate)
D = diffusion coefficient (dissolution rate constant)
A = area of the surface
(triangle)C = the concentration difference across the boundary layer (=C(s) - C)
C(s) = API concentration next to solid surface = saturated = solubility
C = API concentration in bulk solvent
h = thickness of boundary layer

Question 19

Which has a faster dissolution rate: smaller or larger particles?

Answer 19

Smaller particles have a faster dissolution rate - have a larger surface area per unit mass than larger particles

Question 20

Define: Bulk density

Answer 20

The volume occupied by a given mass of powder (g/cm3)

Question 21

What implications does a low bulk density have?

Answer 21

A low bulk density = large volume = large tablet = inconvenient