Product Preservation 1 Flashcards
Pharmaceutical products must be stable and meet GMP requirements for quality, safety, efficacy and be acceptable to patients. What does GMP stand for?
Good manufacturing practices
The activities of contaminating organisms in a product can…
- lead to product spoilage, rendering the product unfit for use, and undermining its efficacy.
It can also cause a health hazard to patients and users of the product.
Is a spoilage organism more dangerous in a food or medicine?
Medicine!
What are preservatives used and not used for?
- Used to prevent possible contamination during storage, limit growth of contaminants and prevent spoilage.
- Should NOT be used to deal with contamination/ spoilage from heavily contaminated raw materials or poor manufacturing process
Contamination is defined as
the introduction of organisms into or onto a product
Does contamination always lead to spoilage?
NO
What are 4 sources of contamination?
- raw materials
- manufacturing sources
- environment
- in-use (storage and use)
Raw material contamination examples?
Water
Excipient and active ingredients (especially natural)
What is RAW water contaminated with and what should it be free from?
- typically water borne bacteria (genera)
- other MOs may be present
- SHOULD BE FREE FROM faecal coliforms e.g. E.coli
How can you achieve purified water? What processes?
- reverse osmosis
- distillation
- ion exchange
After production of purified water, what is it treated by?
Filtration or UV light
What organism grows on purified water?
Pseudomonas aeruginosa
How is purified water STERILISED?
Autoclave
In order to prevent bacteria multiplying and increasing the endotoxin load, what temperature is water stored at? (for sterile medicines?)
> 80 degrees
Spore forming organisms are common on mined minerals and ___ materials of ______ origin
raw
plant
Environmental contamination may come from?
- Air
- Personnel
What are sources of human contamination? (From what body part?) and give examples of the bacteria that colonise there.
Skin scales
- Staphylococcus aureus and other staphylococci
- Pseudomonas aeruginosa
- Streptococcus pyogenes
- Micrococci
Saliva
- Streptococci
- Bacteroides spp
Gut bacteria
- Faecal coliforms (e.g. Escherichia coli)
- Bacteroides spp
On manufacturing sources; equipment, how is a bacterial biofilm formed?
- adhesion of proteins to surface, initial reversible attachment of bacteria to surface
- irreversible attachment of bacteria and formation of micro-colonies
- Production of exopolysaccharide matrix and recruitment of other species.
- Consolidation of multispecies biofilm
- sloughing of outer layers
Examples of contamination while in use?
- During storage
- In use by patient, consumer, nurse or doctor
What are some other factors affect the risk of contamination and spoilage?
- type and size of microbial inoculum
- storage and temperature
- packing design
- nutritional factors, moisture content and water activity
- duration of use/ storage of product
Consequences of contamination… how can you tell it is contaminated?
- visible growth (e.g. fungal colonies, turbidity, colour change)
- organoleptic properties (smell/ taste weird, tactile effects; grittiness)
- loss of active ingredient/ excipients
What are some toxic effects/ health hazards? What is it caused by and what can it cause?
- Production of toxins: LPS, exotoxins, myotoxins
- can cause infection in patients.
LPS is inactive through the _____ route but serious effects if enter the bloodstream through infusions or ______; can induce septic and fatal febrile shock
oral
injections
In hospitals contamination of ____ dose products can serve as vehicles for spread of disease
multi
What are some strategies for preserving products?
- pH manipulation
- water activity manipulation
- low temp storage
- use of preservatives
pH can be manipulated to ______ to reduce risk of spoilage. Useful for ___ and some domestic products but less useful for ______.
more than 8
foods
pharmaceuticals
Aw: a parameter that describes the amount of free water in a solution (water activity). Therefore, the ______ the Aw , the better
lower
No organisms are expected to growth at an AW of ____ or below. These products may not need addition of preservatives
0.5
Problems with modulation of Aw for preservation (“dry” products)
- To use Aw for preservation, the Aw must be maintained throughout the life of the product
- Difficult to predict changes in Aw during storage
- Many dry products are ‘hygroscopic’ and absorb water
- Water may condense on the surface of dry products during storage e.g. steamy bathroom
How can you overcome the problem of Aw stability with hygroscopic drugs?
- Add film coat to limit water reuptake
- package in foil strips to prevent uptake of moisture (most expensive but more effective)
Problem with Aw reduction in relevance to efficacy of preservatives?
May reduce efficacy of preservatives e.g phenol and paraben
What are some commonly used esters?
- Acids and Esters e.g. sorbic acid; pH
Properties of ideal preservative
- broad spectrum of antimicrobial activity
- rapid antimicrobial action/ rate of kill
- chemically stable and effective at all pH conditions
- compatible with excipients and packaging materials
- cheap and safe
