Drug stability Flashcards
1
Q
Drug stability
A
- If a medicine retains 90% of its activity
- Has 90% of stated concentration of ingredients
- Contains effective levels of preservatives
- Shows no visible cracksDiscolouration
- Is not toxic or irritant
- Shelf life is the period that elapses before the above ceases to be true
2
Q
Common question: should you use out of date medicines
A
- US study showed theophylline could keep for >30years
- Another study 88% of 122 drug products retained stable for 5 years after the expiry date
- Obviously liquid preparations will deteriorate more rapidly
- It depends on the medicine but the official answer is no
3
Q
Why medicine deteriorate
A
- Oxidation: caused by
- Instability of medicine (many double bonds, for example)
- Presence of catalysts, such as light, heat, metals
- Changes in pH
- Reaction with solvent (if liquid formulation)
4
Q
Medicine deterioration
A
- Temperature effects are particularly important
- A reduction in temperature increases the solubility of oxygen in the water
- So increasing oxygen availability for reaction with the medicine
- Despite the fall in temperature acting to slow the reactions
- Overall, some medicines in solution deteriorate more quickly in solution in lower temperatures due to top the oxygen availability (such as catecholamines)
5
Q
Redox potential
A
- For many drugs, the ease with which they can be oxidised is calculated by using the NERST EQUATION
6
Q
NERNST EQUATION
A
- Can be used to predict how stable a new drug might be
- Tields an E value- a high E value means the agent is harder to oxidise
- Increase the hydrogen ion levels, raises the E, so acidic solutions stabilise many drugs
- pH 3-4 is most effective, but an acid injection hurts
- Adrenaline E is 0.52, Ascorbate is 0.14, so the ascorbate is preferentially oxidised and preserves the drug
7
Q
Auto-Oxidation
A
- Medicines which are highly lipophilic are subject to autoOxidation
- This can be triggered by free radicals, or light
- The auto-oxidation of oils occurs in four stages and this proceeds is also applicable to all edible oils
- The process can even occur in cell lipid membrane
8
Q
Stages of lipid/oil Oxidation
A
- IntiationRH becomes R and H
- This can occur through light or heat catalysis
- This process leads to the next, which an amplification step
- Propagation R: reacts oxygen forming peroxy radicals, which react with other RH’s forming more radicals
- Oxygen will fuel the reaction as long as it is present, it’s a forest fire effect
9
Q
Oil oxidation- Termination
A
- Various radicals react with each other to form inactive products which cannot sustain the reaction
- Eventually the oil is completely oxidised and becomes rancid
- All medicines/foodstuffs which are kept in oils and oil-based environments are vulnerable to auto-oxidation or rancidity
10
Q
Protection of medicines
A
- Remove all oxygen
- By spraying (bubble with He, displace oxygen or canning boil and let steam drive oxygen out than seal, and vacuum preserves agents)
- Use an inert gas to preserve drugs
11
Q
USE of antioxidants
2 types
A
- Anti-oxygens: these preserve oils from auto-oxidation
- Reducing agents: preserve water soluble drugs from oxidation
12
Q
Antioxygens
A
- All oil soluble
- Generally phenols like butylated hydroxyanisole (BHA)
- These react with radicals and usually terminate them
- Sterically hindered butylated hydroxytoluene (look up structure) is better, as it does not form radicals itself
- Look in foodstuffs for BHA and BHT, often used together e.g. in bags of crisps
- Very long-lasting protection
13
Q
Reducing agents
A
- These are preferentially oxidised and afford protection until consumed
- E.g. tartaric acid, ascorbate, sodium metabisulphate
14
Q
New Medicines
A
- Firstly, their stability must be investigated and the routes of decomposition determined
15
Q
A
