W6 Stability of Medicines

Question 1

What are the 4 chemical degradation reactions?

Answer 1

Hydrolysis
Oxidation
Photodegradation
Polymerisation and Dimerisation

Question 2

Hydrolysis reduction
The rate of hydrolysis is reduced by:

Answer 2

• Dry formulations (powder for reconstitution, solid dosage form)
• Adjusting pH to maximum stability in aqueous solution
• Storage temperature
• Coating
• Choice of packaging

Question 3

Circumvention of auto-oxidation

Answer 3

• Remove initiators
• Chelation of trace metals with chelating
  agents: ethylene diamine tetraacetic acid
  (EDTA), citric acid & tartaric acid
• Exclude O2
• Sparge liquids with inert gases such as
  nitrogen to displace oxygen

Add free-radical scavengers/antioxidants
* Butylated hydroxytoluene (BHT) more readily oxidised than oils, used to
stabilise fatty/oily products
* Ascorbic acid possesses lower redox potential than drug, more readily
oxidised

Question 4

Photochemical degradation

Answer 4

Energy of photon increases with decreasing wavelength

Question 5

Polymerisation

Answer 5

• A process by which two (dimerisation) or more identical drug
  molecules combine together to from a complex molecule
• UV radiation induces the polymerisation of chlorpromazine (in anoxic
  conditions)

Question 6

Photolysis

Answer 6

• Decomposition by light
• Photolysis of the pentacyanonitrosylferrate (II) ion in sodium
  nitroprusside (administered by IV infusion for the management of
  acute hypertension)
• Protected from light, stable for ~1 year
• Exposed to normal room light, a shelf life of only 4 hours

Question 7

Circumvention of photochemical effects

Answer 7

• Exclude from light by
• Storing in the dark
• Packaging in foil
• Filter out light by
• Storage in amber glass or
• Coating tablets with pigmented polymers

Question 8

Zero order reactions

Answer 8

Half-life is dependent of the initial concentration
y=mx + c
Straight slope -ve gradient

Question 9

First order reaction

Answer 9

The rate of degradation of A is directly proportional to its concentration

Question 10

Second order reactions

Answer 10

The rate of degradation of A is directly proportional to its concentration and the concentration of the reactant B

Question 11

What are the 3 rates of degradation?

Answer 11

Zero Order, First Order, Second Order

Question 12

How much degradation of a medicine is reasonable?

Answer 12

5 – 10% loss limit over total shelf life (~ 5 years)

Question 13

Arrhenius equation

Answer 13

k=Ae-^Ea/RT

where:
k= rate constant of degradation
e^-Ea/RT = fraction of the number of successful collisions
Ea= activation energy
R= Molar gas constant (8.31 JK-1 mol-1)
T= Temperature (Kelvin)

Question 14

how to convert from lnk to k

Answer 14

Raise e^ of that number
e.g. lnk= -5.298
k= 0.005