Formulation of Advanced or Complex Medicines 4 Flashcards
How can oxidation be prevented in parenteral products?
Antioxidants
- material preferentially oxidised in comparison to the active medicament
Chelating agents
- enhance antioxidant effects
What properties must an antioxidant used in parenteral products have?
High solubility
Stable
Compatible
Non-toxic
Give examples of how to sterilise parenteral products
Autoclaving
Dry heat
Filtration
Radiation
Gaseous methods
What options are there for the containers/closures for parenteral products?
Glass vs plastic
Single dose vs multi dose
Novel containers
- pre-filled syringes
- pre-filled pumps
What overage should be used when making parenteral products?
10% of volume
What is a pharmaceutical excess?
Excess of product made to allow for losses during manufacture
What Quality Control issues are there when making parenteral products?
Sterility testing
Test for bacterial endotoxins or pyrogens
Uniformity of content of active ingredient
- mass if it’s a powder injection
Particulate contamination
- only in specific products
Labelling
- information on original container
- ampoule
- information on outer container
Overlabelling
- hospital usage
What Quality Assurance protocols are in place when making parenteral products?
Manufacturing worksheets
Calculations
Quality Control
Which products is sterilisation an essential stage in the processing of?
Parenteral administration
Contact with broken skin, mucosal surfaces or internal organs
Microbiological materials, soiled dressings and other contaminated items
What is terminal sterilisation?
Product is sterilised in its final container (wherever possible)
How is terminal sterilisation carried out, wherever possible?
Appropriate additional treatment applied
- e.g. heating of the product in its final container
What is the function of the container and closure?
To maintain the sterility of the product throughout its shelf life
What should be used in terminal sterilisation is not possible?
Filtration through a bacteria-retentive filter
What are the five methods of sterilisation of pharmaceutical products recognised by the BP?
Moist heat
- steam sterilisation
Dry heat
Gamma or electron radiation
Ethylene oxide gas
Filtration
Give two examples of sterilisation that relies on physical processes
Elevated temperature
- moist heat
- dry heat
Irradiation
- gamma-rays
- high energy electrons
Give three examples of sterilisation that relies on chemical processes
Biocidal agents
- glutaraldehyde
- peracetic acid
Reactive gas
- ethylene oxide
- Low Temperature Steam Formaldehyde (LTSF)
- chlorine dioxide
Gas plasma
Give an example of a microbial remove process used in sterilisation
Filtration
What factors determine the choice of sterilisation method?
Level of microbial contamination
- bioburden
Properties of the product to be sterilised
- aqueous
- oily solutions
- emulsions
- dry powder device
- metal
- plastic
- combination of materials
- natural
- e.g. cotton
- synthetic materials
- e.g. Gortex
Effect of method on product
- physical
- chemical
Effect of method on product container/package
- physical
- chemical
What is the optimum outcome for sterilising pharmaceutical products?
Ensure maximum microbial kill/removal with minimum product deterioration
What is the inactivation kinetic?
Achieving guaranteed sterility is mathematically possible
- product will need to be exposed to an infinite exposure time
What is the probability of microbial survival determined by?
Number of contaminants
Type
Resistance properties
Environmental conditions existing within the sterilisation process
What is the Sterility Assurance Level (SAL)?
Degree of assurance for a sterilising process to render a population of products sterile
How is the Sterility Assurance Level determined?
The probability of a non-sterile item being present within the product population post sterilisation
