Preservatives Flashcards
Preservation of pharmaceutical products
Sterile and non-sterile preparations
Parenteral, ophthalmic, oral, topical and otic (BP) preparations
Cosmetics
Preservation- Background
Prevention of microbial spoilage of products and decreasing risk of infection when the preparation is administered.
Preservatives should prevent the proliferation of micro-organisms in non-sterile products.
Preservatives should kill micro-organisms in sterile products.
Self sterilising products
Contain more than 15% alcohol (elixirs, spirits, tinctures)
High concentration of sugars ((>85%) syrups (exosmotic effect)
High concentration of sugar (>85%) and sufficient polyol (sorbitol, glycerin, propylene glycol)
Ionizing radiations
Preservation of food (limited due to consumer’s concerns)
High pressure
Preservation of food and drink (300-700 Mpa), doesn’t alter taste of food
Favourable conditions for microbial growth
Water activity (tablets)
pH (acidic pH)
Temperature (low temperature)
Sources of contamination
Raw materials
During manufacture- contaminated equipment, water, air operators, packaging materials
During use- re-use, multi-dose containers
Spoilage can be caused by:
Low levels of acutely pathogenic micro-organisms
Higher level of opportunistic pathogens
Toxic metabolites can persist even after death of the original contaminants
Physical changes due to microbial contamination
Microbial growth has initiated significant physical or chemical deterioration of the product:
Breakdown of emulsions, visible surface growth on solids, formation of slimes, pellicle or sediments in liquid
Changes can be accompanied by production of gas, odours or unwanted flavours
Clinical implications
From local infections (wound infection) to systemic infections (parenteral products)
Septicaemia after infusion contaminated solution (gram-negative)
Ophthalmic infections (eye drops, eye cosmetics)
Degree of contamination is high- endotoxic shock
Functional categories
Alcohol (ethanol)- disinfectant, preservative and solvent
Benzalkonium chloride- disinfectant, preservative, solubilising agent, wetting agent
Benzethonium chloride- preservative, wetting and solubilising agent
Benzyl alcohol- preservative, local anaesthetic (10% v/v), solubiliser (5% v/v)
Boric acid- preservative, buffering agent
Cetylpyridinium chloride- disinfectant, preservative, solubilising agent, wetting agent
Chlorobutanol- preservative, plasticizer
Other ingredients labelled as antimicrobial preservatives
Butylene glycol, calcium acetate, propylene glycol
Other ingredients not labelled as anti-microbial but have activity
Non-ionic surfactant, ionic surfactant, amphoteric compounds
Testing for preservative efficacy
Test model offering manufacturers guidance, not intended for routine use, assess efficacy of preservative system during product development, reflect storage conditions (container, temperature and time), essential part of quality control
Aims of testing for preservative efficacy
Measure products ability to resist microbial contamination
Predict long term preservative efficacy during use and storage
Assess the probability of recontamination
Preservative efficacy test (PET): inoculum
Aspergillus niger
Candida albicans
Pseudomonas aeruginosa
Staphylococcus aureus
Relevant industrial isolates
Preparation of inoculum well-described (media, temperature, time of incubation)
Harvesting inoculum (spores of A. niger)
Counting microbial concentration prior to test challenge
PET test procedure
Inoculate a series of containers of the product with a suspensions of one of the test organisms
Volume of the suspension not to exceed 1% of the volume of the product
Incubation at 20-25c, protected from light
Sampling at zero hour and at appropriate intervals according to the type of the product
Determination of viable count: plate count, membrane filtration or most probable number
Validation of PET
Verify its ability to demonstrate the required reduction in count of viable micro-organisms
Criteria for acceptance of PET
Significant fall or no increase in the number of micro-organisms in the inoculated preparation after the times and at the temperatures prescribed
Different performance criteria are required depending upon the formaultion
Limitations of PET and potential development
Laboratory evaluation instead of evaluation in situ
Stringency of the tests
Use of rapid detection technique
Real time monitoring
Testing for preservative activity: regulatory aspect
Manufacturers must justify steps taken to assess and minimise the risk of microbial contamination and spoilage and demonstrate efficacy of the preservative system
When preservatives are deemed necessary:
Preservative efficacy test to demonstrate adequate protection throughout life of product
Evidence of safety of preservative
Reasons for inclusion
Details of labelling and methods of control in the finished product
What are the other tests for preservative efficacy?
Multiple challenge test (cosmetics)
Determination of D-value (decimal reduction time)
Test in loco (cosmetics)
