Formulation of Advanced or Complex Medicines 4

Question 1

How can oxidation be prevented in parenteral products?

Answer 1

Antioxidants
- material preferentially oxidised in comparison to the active medicament
Chelating agents
- enhance antioxidant effects

Question 2

What properties must an antioxidant used in parenteral products have?

Answer 2

High solubility
Stable
Compatible
Non-toxic

Question 3

Give examples of how to sterilise parenteral products

Answer 3

Autoclaving
Dry heat
Filtration
Radiation
Gaseous methods

Question 4

What options are there for the containers/closures for parenteral products?

Answer 4

Glass vs plastic
Single dose vs multi dose
Novel containers
- pre-filled syringes
- pre-filled pumps

Question 5

What overage should be used when making parenteral products?

Answer 5

10% of volume

Question 6

What is a pharmaceutical excess?

Answer 6

Excess of product made to allow for losses during manufacture

Question 7

What Quality Control issues are there when making parenteral products?

Answer 7

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

Question 8

What Quality Assurance protocols are in place when making parenteral products?

Answer 8

Manufacturing worksheets
Calculations
Quality Control

Question 9

Which products is sterilisation an essential stage in the processing of?

Answer 9

Parenteral administration
Contact with broken skin, mucosal surfaces or internal organs
Microbiological materials, soiled dressings and other contaminated items

Question 10

What is terminal sterilisation?

Answer 10

Product is sterilised in its final container (wherever possible)

Question 11

How is terminal sterilisation carried out, wherever possible?

Answer 11

Appropriate additional treatment applied
- e.g. heating of the product in its final container

Question 12

What is the function of the container and closure?

Answer 12

To maintain the sterility of the product throughout its shelf life

Question 13

What should be used in terminal sterilisation is not possible?

Answer 13

Filtration through a bacteria-retentive filter

Question 14

What are the five methods of sterilisation of pharmaceutical products recognised by the BP?

Answer 14

Moist heat
- steam sterilisation
Dry heat
Gamma or electron radiation
Ethylene oxide gas
Filtration

Question 15

Give two examples of sterilisation that relies on physical processes

Answer 15

Elevated temperature
- moist heat
- dry heat
Irradiation
- gamma-rays
- high energy electrons

Question 16

Give three examples of sterilisation that relies on chemical processes

Answer 16

Biocidal agents
- glutaraldehyde
- peracetic acid
Reactive gas
- ethylene oxide
- Low Temperature Steam Formaldehyde (LTSF)
- chlorine dioxide
Gas plasma

Question 17

Give an example of a microbial remove process used in sterilisation

Answer 17

Filtration

Question 18

What factors determine the choice of sterilisation method?

Answer 18

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

Question 19

What is the optimum outcome for sterilising pharmaceutical products?

Answer 19

Ensure maximum microbial kill/removal with minimum product deterioration

Question 20

What is the inactivation kinetic?

Answer 20

Achieving guaranteed sterility is mathematically possible
- product will need to be exposed to an infinite exposure time

Question 21

What is the probability of microbial survival determined by?

Answer 21

Number of contaminants
Type
Resistance properties
Environmental conditions existing within the sterilisation process

Question 22

What is the Sterility Assurance Level (SAL)?

Answer 22

Degree of assurance for a sterilising process to render a population of products sterile

Question 23

How is the Sterility Assurance Level determined?

Answer 23

The probability of a non-sterile item being present within the product population post sterilisation