Microbial Stability

Question 0

How can you tell when a product is microbial instable?

Answer 0

Localised or gross spoilage.
Release of unpleasant smelling or tasting.
Discolouration and pigmentation.

Question 1

What defines microbial instability?

Answer 1

Microbial growth and initiation of physics-chemical deterioration of the product.

Survival of pathogenic microorganisms

Presence of toxic metabolites

Question 2

Name 5 consequences of microbial instability

Answer 2

1) Safety
2) Efficacy
3) Quality
4) Patient’s acceptability
5) Commercialisation

Question 4

Briefly, what is the difference between Sterile products and Non-sterile products, on terms of microbial instability?

Answer 4

Sterile product should have “no organism” present.

Non-sterile products should have limited of micro-organism present, but must have an absence of ‘objectional’ organisms.
E.g. Staph aureus, E. Coli, Salmonella, Pseudomonas

Question 5

What organisms does the TGA restrict for products for oral use in non-sterile products?

Answer 5

E. coli

Salmonellae

Question 6

What organisms does the TGA restrict for products for topical use in non-sterile products?

Answer 6

Pseudomonads

Staph Aureus

Question 7

Briefly explain how Microbial limit testing methods (2 methods)

Answer 7

1) Product is sampled
2) Diluted or dissolved in a suitable solvent (e.g. water)
3) Aliquots are poured or plated onto nutrient agars
4) Incubated to detect the colony-forming unit/gram or mL

or membrane filtration method:

1) Product solution is filtered using a sterile membrane filter
2) Membrane filter is then incubated on the surface of the nutrient agar place or added into the nutrient broth to detect growth

Question 8

List some sources of microbial contamination (8)

Answer 8

1) Raw materials - drugs, excipients
2) Environment
3) Personnel
4) Equipment and containers
5) Packaging materials
6) Manufacturing process
7) Storage
8) Usage and handling

Question 9

What 4 things does microbial stability depend on?

Answer 9

1) Physico-chemical properties of the formulation ingredients
2) Type of contaminants
3) Quantity of contaminants
4) Risk of contamination

Question 10

What can lead to microbial instability?

Answer 10

Product ingredients and metabolites are sources of energy and precursors for micro-organism survival and multiplicaiton

Question 11

List some susceptible formulation ingredients that can either be metabolised by micro-organisms or used as a substrate for growth.

Answer 11

Drug molecules
Sweeting, flavouring and colouring agents
Fats and Oils
Preservatives and disinfectants
Humectants
Surfactants
Polymers

Question 12

List the 5 factors that affects microbial instability

Answer 12

1) Growth factors in the formulation
(e. g. nutrients as substrates for growth)

2) Risk of contamination
(level of exposure)

3) Temperature
(m. o. can grow between 20-60°C)

4) pH
(neutral pH promotes growth)

5) Packaging materials
(prevents m.o. entry, but can be nutrients as well)

Question 13

What are the 7 formulation considerations for microbial stability?

Answer 13

1) Preservatives
2) pH of formulation
3) Additives
4) Packaging design
5) Storage conditions
6) QA/QC
7) Postmarketing surveillance

Question 14

What is the purpose of preservatives? (3)

Answer 14

Antimicrobial agents to:

1) Protect from microbial spoilage during storage and use
2) Protect from contamination during manufacture
3) Protect the user from infections

Question 15

What does Preservative activity depend on? (4)

Answer 15

1) Type and Concentration of preservative
2) Number and Type of micro-organisms
3) Ionisation state of preservative
4) Temperature

Question 16

How might addition of preservative compromise the chemical stability of the drug?

Answer 16

It can alter the formulation of the pH

Question 17

How does temperature affect preservatives?

Answer 17

Warmer temperatures (e.g. room temp) can decrease the preservative concentration, thus decreasing its antimicrobial activity

Question 18

What’s one common conflict that may arise when using buffers in formulations?

Answer 18

A buffer can create an unfavourable growth environment. But buffers are also required to adjust pH to stabilise the formulation. This can be an issue when it’s microbial stability vs. chemical stability.
E.g. a formulation is stable under basic conditions (high pH), but the preservative is no longer effective under these conditions.

Question 19

What are Additives?

Answer 19

Ingredients added to reduce water activity
(free water concentration available for growth)

E.g. PEG, sorbitol, glycerol

Question 20

How can foil or seal packaging protect from microbial instability?

Answer 20

Reduces moisture content & prevents contamination

Question 21

How can packaging increase microbial instability? (2)

Answer 21

1) Adsorption and partitioning of preservatives

2) Packaging materials may also support growth

Question 22

What might refrigerating a product (4-8°C) help prevent?

Answer 22

Warm-cold cycles that might lead to crystal growth. Thus it has an effect on drug solubility

Question 23

What is the difference between QA & QC?

Answer 23

Quality Assurance (QA) involves planning and monitoring of all stages of product manufacturing (e.g. sterilisation methods, training & education, and environmental monitoring of air, surfaces)

Quality Control (QC) involves end product testing (e.g. sterility testing & endotoxin testing)

Question 24

Briefly explain Postmarketing surveillance and how it helps microbial stability.

Answer 24

Monitor product in-use performance.

Procedures for responding customer feedback or complaints about the product.

Data modification of design and processing to improve microbial stability profile of produce