Microbial stability of Pharmaceuticals

Question 1

Microbial Instability

Answer 1

• Microbial growth
• initiation of physic-chemical deterioration of the product
• survival of m.o
• presence of toxic microbial metabolites

Question 2

Consequences of microbial contamination

Answer 2

safety, efficacy, quality, patient’s acceptability, commercialisation

Question 3

Non-sterile products

Answer 3

• limit testing of product samples of total aerobic, yeast and mild counts
• use specific media to detect objectionable organisms
• methods to be validated

Question 4

Factors affecting microbial stability

Answer 4

1. Growth factors in the formulation
   - nutrient, moisture, oxygen
2. Risk of contamination
   - frequent exposure to sources?
3. Temperature
   - promote growth
4. pH
   - promote/ prevent growth
5. Packaging materials
   - promote/ protect microbial contamination

Question 5

Formulation considerations for microbial stability

Answer 5

1. Preservatives
   - antimicrobial agent
   - may affect pH of the formulation and compromise chemical stability of the drug
2. pH of the formulation
   - buffer the product to create unfavourable environment for growth
   - affects preservative activity (ionisation state)
3. Additives
   - reduce water activity
   - effect on pH
4. Packaging design
   - reduce moisture, prevent contamination, lower oxygen
5. Storage conditions
   - refrigerate, freeze
6. QA / Qc
   QA: -planning and monitoring all stages of product manufacturing
   - personelle training and education
   - environment monitoring
   QC: - end product testing
   - endotoxin testing
7. Postmarketing surveillance
   - Monitor in-use product performance
   - procedures for responding customer feedback and complaints about the product
   - modify design and improve microbial stability profile of product