MDM: Packaging and stability Flashcards
What is drug stability?
The ability of a pharmaceutical dosage form to maintian its physical, chemical and therapeutic properties within the time used by the patient
What are chemical instabilities
- oxidation
- hydrolysis
- photodegradation
- temperature
- polymorphic changes
- isomerism
What are physical instabilities?
- Water content
- pH
- appearance
- rheology
- SDF - srength of tablet and dissolution
- suspension - redispersability
- Precipitation/ particle size
What are examples of other types of instabilities?
- Packaging: absorption, adsorption, leaching
- microbiological
- inncorrect storage/ usage
What are processing instabilities in SDFs?
- Oxidation: Movement of particles in mixing and granulation
- Hydrolysis: use of aqueous granulation solvent or humidity of air
- Thermal: heat used for drying granulation or heat used in coating process
How can instabilities for SDFs be avoided?
- identify Cause and remove it:
- Water (hydrolysis) - don’t granulate
- thermal degradation - remove need for heat
- air (oxidation) - Do process under N2 blanket
- Light degradation - find problrmatic wavelength and use light without
Reduce effects:
- •Add anti-oxidants to formulation
- •Reduce water content in granulating solution.
- •Dehumidify the environment
- •Use lower temperatures (non-aqueous granulation).
- •Minimise the length of time the materials are handled in the presence of light
How to over come hydroylsis in liquid/ semi- solid dosage forms
- Form a complex
- Modify chemical structure
- Solubilise in micelles
How to protect Liquids/ semi solids from oxidation
Removal of O2:
- use inert gas to displace air above the product
- boil water immediately before use
- use well filled containers
Protection from light:
- Energy from light fuels oxidation process therefore packaginf methods are used to protect it from light:
- Cartons, light resistant containers
pH control
- Oxidation prodcues H+ ions therefore and acidic envirmoent will help prevent it
Solubilisation:
- Oxygen is less soluble in an oily component than in an aqueous so dissolving the drug in oil to prodcue an emulsion will protect it
What other stability issues are there with Liquid/ ss forms? How do you prevent these?
- Manufacture in suitable enviroment
- add preservative to prevent microbial growth
- parabens and phenoxyethanol
What packaging instabilities is there?
- Drug not sufficently protected by packaginf or packaging has materials which coulc potenital leach out into product
Whar types of stability tests are done?
- Preformulaiton - stress testing done on drug ONLY. Determines potential areas of drug degradation pathways
- Binary mixes - 1:1 ratio of drug and excipents. Tested at high temperatures or using DSC. Can have tertiary mixtures
- Formulation and container development -
- Post authorisation tsudies - supports kucebcubg aookication
Talk about expiry dates
All medicinal products have them
- Shelf life - time taken for drug to reduce to 95% of its orginal value
- SS/ liquids have shorter SL
- Powders have 2 SL - 1 dried and 1 reconstitued
What are the reasons for packaging?
- Patient loyalty
- Product identity
- protect the product
- patient compliance
- presnetation of the information
- tamper protection and child resistanr
What packaging is used for liquids?
- Glass: Good moisture and light protection. Amber or opaque bottles. 3 types of glass
- Plastic: Opaque bottles used. Provides some light protection not as good as metal/ glass. Moisture protection depends on polymer used
- Aluminium: Same moisture protection and better light protection. Internal surfaces need to lacqured to prevent interactions
What packaging is used for semi solids?
- Glass bottles: used if materials interact with plastic and for exemperous preperations
- plastic bottles/ jars: see Liquids
- Metal: aluminium. Lacqured internal surface
What are additional requirements of bottles?
- Cap
- foil
- Shrink sleeve
- ullage takeup
What are the 3 methods of filling liquids/ SS?
- Weight filling: Bottle on tared balance and filled to correct weight
- level filling: Tube filling with another tube at the correct level removing excess
- Volumetric filling: Fixed measuring cylinder or adjustable cylindrical pump
What are blow fill sealed techniques used for?
- Expensive or specialised equipment
- parentals
- not suitable for heat sensitive products
How are blister packs manufactured?
- Thermoformed - by heat and pressure or vaccum
- Mechanically formed - by pressure to top surface
What types of filling is there into blister packs?
- Random filling - moves through hopper into blister pockets
- Guided filling - tubes guide product down into pockets
- pick and place systems - suction pads/ mechanical grippers pick and place into pocket
How is intergrity of blister packs measured?
- Empty blister pack
- PLaced in coloured liquid
- pressure applied for set time
- Check if liquid in pockets
- repeat with product in blisters
What are problems associated with blister packs?
Banana skinning - logitudinal or transverse distortion due to differences in expanaion coefficents of forming and lidding materials
Put in straightening ribs
What determines what film is required to cover blister packs? what are they made off?
Depends on level of protection for moisture
aluminium, paper, plastic
What quality assesment controls are required?
- Right quantity
- no damage to packaging
- whats on the label is in the packaging
- sterility of product
What does the 2nd/ outer packaging provide?
- Patient information
- Physical stability during transport of package
