Stability

Question 1

Why is stability testing important?

Answer 1

• Medicines degrade over time, affecting safety and efficacy.
  
  • Determines shelf life (how long a product remains safe).
    Expiry date = end of shelf life.

Question 2

Factors affecting stability

Answer 2

1. Temperature
2. Chemical Stability
3. Light & Oxygen

Question 3

How does temperature affect stability

Answer 3

• Increased temperature = faster degradation.
  
  • Cold storage (2–8°C) slows degradation.
  • Freezing (< -15°C) can harm some drugs (e.g., amoxicillin in solution).
    Transport & storage risks: exposure to high temperatures.

Question 4

Chemical stability

Answer 4

• Hydrolysis (reaction with water) – prevented by replacing water with another solvent.
  
  • Solvent choice: Consider toxicity & compatibility.
  • Solid forms are generally more stable than liquid forms.
    pH sensitivity: Some drugs degrade faster at acidic or basic pH.

Question 5

Catalysis and pH effects

Answer 5

• Catalysts speed up degradation (H₃O⁺, OH⁻, buffer ions).
  
  • Example: Phosphate & acetate catalyse chloramphenicol hydrolysis.
  • Use borate buffer instead (non-catalytic).
    pH affects ionisation, changing degradation rates.

Question 6

How does light & oxygen affect stability

Answer 6

• Photodegradation – prevented using tinted/opaque packaging.
  
  • Oxidation – prevented by:
    ○ Flushing with inert gas (N₂, Ar).
    ○ Antioxidants (e.g., ascorbic acid, α-tocopherol).
    Chelating agents (e.g., EDTA) to bind metal ions (Cu²⁺, Fe³⁺) that catalyse oxidation.

Question 7

Physical Stability & Stress testing

Answer 7

1. Liquid dosage forms
2. Sorption and container effects
3. Preformulation & Stress testing

Question 8

Liquid dosage forms testing

Answer 8

• Solutions: Risk of precipitation (reduces efficacy, poor appearance).
  
  • Suspensions: Risk of caking, particle growth (leads to inaccurate doses & grittiness).
  • Emulsions & creams: Risk of:
    ○ Creaming, cracking (phase separation).
    Loss of viscosity (affects application).

Question 9

Sorption & Container Effects

Answer 9

• Sorption = adsorption + absorption.
  
  • Non-polar drugs can stick to plastics & rubber (e.g., diazepam).
  • Volatile components lost to rubber lids.
    pH affects sorption (unionised form sorbs more).

Question 10

Performulation & Stress Testing

Answer 10

• Identifies stability issues early (e.g., oxidation, hydrolysis).
  
  • High-temperature storage accelerates degradation.
  • Uses Arrhenius Equation to predict stability at room temperature.
  • Limitations:
    ○ Different degradation reactions may occur at high temp.
    ○ Unreliable for precise shelf-life predictions.
    Temperature cycling (freeze-thaw) tests effects on emulsions, suspensions, solutions.

Question 11

Long term stability testing

Answer 11

Real storage conditions over at least 12 months
Test for:
* Drug & excipient stability
* pH, microbial contamination, physical properties
Accelerated testing under raised temperature and humidity to detect problems faster

Question 12

Climatic zones

Answer 12

• Testing conditions vary by region (e.g., hotter/humid climates need special testing).
  Packaging matters – should be the same as the final product.

Question 13

Testing protocols

Answer 13

• At least 3 batches tested.
  
  • Liquid formulations stored inverted (to test cap interaction).
  • Sampling intervals:
    ○ Every 3 months (year 1).
    ○ Every 6 months (year 2).
    ○ Annually after that.
    Control humidity unless irrelevant (e.g., aqueous solutions in glass).

Question 14

Assessments for liquid dosage forms

Answer 14

• Solutions: Precipitation, clarity, pH, viscosity, microbial contamination.
  
  • Suspensions: Dispersibility, rheological properties, particle size.
    Emulsions: Phase separation, droplet size.

Question 15

Evaluation of results

Answer 15

• Set specifications for acceptable degradation (usually >90% drug remains).
  
  • Aesthetic properties (appearance, smell, taste) must be acceptable.
  • Shelf life = shortest time from tested batches.

Question 16

Summary of product testing - stability

Answer 16

• Chemical, physical, and microbiological degradation impact medicine performance.
  
  • Stability testing ensures efficacy & sets shelf-life.
  • Formulation adjustments (e.g., buffers, antioxidants, packaging) improve stability.
    Regulatory protocols require extensive testing (preformulation, stress, and long-term studies).