packaging and assessment Flashcards
how is pharmaceutical quality measured and what is it affected by?
affected by: - starting materials - manufacturing process - packaging and transport - storaging measured by: - physical and chemical analysis
what does microbiological quality depend on?
- bioburden
- bacterial endotoxins
- pyrogens
- sterility
what is a special/unlicensed medicine?
manufactured for human use and has been specially prepared to meet a prescription ordered for individual patients without need to hold a marketing authorisation for the product
- can be supplied for individual patients need
- need a mnaufacturer’s special license
what is the aim of bioequivalence?
to determine if two pharmaceutical products demonstrate in vivo biological equivalence
- generic medicines must prove bioequivalence
- allows patient compliance and reassure them they have the same product and effect
how can we establish bioequivalence?
use the PK parameters
- plasma conc. vs time curves
- Cmax and Tmax
- look at the ADME phases
- Tmax shouldn’t be first sampling point
take blood samples at specific points and with equal time intervals
need to see if its single dose or multi dose; if multi must add more sampling points
want to see full picture of drug exposure
what is the acceptance range for different AUC and Cmax ratio?
AUC should lie within 90% confidence interval; 0.8-1.25 of the reference value
Cmax ratio should lie within 90% confidence interval; 0.8-1.25 of the reference value
- can be tighter for drugs with narrow therapeutic window
what does it mean by specification and how are these set?
a specification is defined as a list of tests, references to analytical procedures and appropriate acceptance criteria
- set to confirm the quality of a drug product
- focus on making drug effective and safe
- need relevant data
what should development of a pharmaceutical product include?
should include the definition of the quality target product profile
should have identification of the critical quality attributes
a control strategy for insurance and ensure product is fit for use
should have a selection of manufacturing processes
what does quality by design mean, require and ensure?
it means that design a formulation that ensures the product has met the pre-defined standards
requires understanding how formulation and manufacturing process influences product quality
it ensures good quality with a good control strategy
what is a quality target product profile?
it is a prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality
must consider
- closures
- dose strength
- drug release and delivery
- intended use, dosage form, route
what is meant by CQA?
critical quality attributes is a physical, chemical or microbiological property that should be within an appropriate limit range or distribution to ensure good product quality
- can be defined for drug substances, drug products and excipients and intermediates
what is a CPP?
Critical Process Parameter is a a parameter whose variability has an effect on CQA and so should be monitored or controlled to ensure good quality
e. g for tablets CPPs could include:
- mixing
- granulation
- drying
- compression
- coating
for a simple immediate release tablet what must the analytical measurements be?
must be
- linear
- accurate
- repeatable
- reproducible
what is the dissolution specification?
75% dissolved in 30 minutes
what is primary packaging?
- direct contact with the product
must be
1. compatible with product
2. have all product info
3. be child resistant but easy to open and re-seal
4. be tamper-resistant or tamper-evident
5. fit for purpose
what is secondary packaging?
- added layer of protection
- information provided
- image of what medication looks like
what is packaging used for and why?
- containment
- shouldnt leak
- no diffusion of product
- be strong during handling - protection
- maintain quality, safety and stability of product through its shelf life - identification, presentation and information
- not direct contact
- essential source of information
what type of bottle packaging can you have?
- Tablet bottles
- made of glass or plastic
- amber coloured
- child resistant cap - medicine bottles
- amber coloured bottle
- fluted amber bottle
- dropper bottle
what are examples of single dose and multi dose containers?
single dose - glass ampoules - infusion bags - single dose syringes - nebuliser ampoules multi dose - multi dose vials or glass bottles - pMDI's - cream jar/bottle/tube - DPI's
what do sealed containers do?t
- prevents product from contaminants such as air or moisture
- a single unit with our preparation
- once opened it is unsealable
what are laminates?
two bits of metal that you put together
paper outside for printing info on
what are blister packs?
- tray with lid used as packaging for tablets and capsules
- provides hermetic seal
- good barrier properties
- tamper-evident
what does strip packaging look like?
the tablets or capsules are heat sealed between two same materials, such as aluminium
protects drug from environment
what are collapsible tubes and ointment jars?
collapsible tubes: - lacquered aluminium and is sealed at both end - can be heat sealed - layer of foil when first opened so needs to be removed for access ointment jars: - wide mouthed - semi solid preparation - risk of contamination by patient
what are risk errors for repackaging?
- right drug
- right number given
- right strength so more checks
what is glass made of? what additives are there?
- silica
- limestone
- soda ash
- cullet
additives
- hardness
- heat - shock resistance
- opacity/clarity
- colour
what are dis/advantages of glass being a packaging?
+ inert and impervious to air and moisture
+ protects from loss of volatiles
+ easy inspection of content
+ can be tinted to block harmful light rays
+ easy to clean and sterilise by heat
- brittleness can release glass fragments
- release of alkaline compounds
- cost and weight
- leaching of glass components
what types of glass is there?
Type I
- borosilicate glass - low leaching risk and less likely to shatter
- low coefficient of thermal expansion ; good for heat sterilisation
- is costy
e.g. ampoules, injection vials
Type II and III glass
- treated soda lime glass for Type II
- soda lime glass similar to food packaging for Type III
what are the uses of Type II and III glass?
Type II - aqueous solutions Type III - non-aqueous parental products - powder for injection
what uses does plastic have?
- packaging of tablets, capsules
- for eye drops or nasal sprays
- as jars or flexible tubes
- blister or strips pack
- infusion bags and for the packaging of SVPs
- as closures for bottles
what do typical plastic containers contain?
- polymers
- polymerisation residues ; impurities
- additives added to modify the properties of the plastic
- processing aids
what is the difference between thermoplastics and thermosetting plastics?
thermoplastics
- can be remoulded and heated more than once
- when it is heated its melt and when it is cooled it hardens
- it is free polymer chains
thermosetting plastics
- can only be heated and moulded once
what plastic additives are there?
- colouring agents
- stabilisers
- UV absorbers
- lubricants
- plasticisers
- flame retardants
- antioxidants
what are the advantages of plastic?
- low cost
- low particle release
- light in weight
- heat sealable
- easily moulded
- multipurpose
- not as inert as Type I glass
what are the disadvantages of plastic?
- has electrostatic charge
- leaching of additives can occur
- adsorption; loss of preservative
- poor barrier properties; to sun rays and gas
what is poly(ethylene)?
PE
- has poor odour barrier
- good compatibility with drugs overall but can sorb preservatives
- low density polyethylene LDPE
- > clear & flexible
- high density polyethylene
- > strong rigid translucent
- > can be pigmented
what is poly(propylene)?
- clear strong and rigid
- heat resistant and excellent barrier to moisture
- good resistance to cracking when bent
- > lower amount of additives and lower risk of adsorption
what is poly(vinyl chloride)?
- variable rigidity, clear and glossy
- heat sensitive
- poor impact resistance
- resistant to oils, fats and flavouring
- need more additives
- not good at protecting against mechanical hazards
what is poly(vinylidene chloride)?
- provides best barrier to moisture gases
- heat resistant
- clear
- flexible
- excellent barrier properties
what is poly(chlorotrifluoroethylene)?
- clear plastic
- heat resistant
- excellent barrier properties
what is poly(styrene)?
- Crystal PS; clear strong rigid but brittle
- poor impact resistance
- poor barrier to moisture, gases and poor chemical resistance
- good for general purpose use
- insufficient heat resistance to resist autoclaving
what is poly(ethylene terephthalate)?
- clear and strong
- good resistance to high temperatures
- good barrier to moisture, gases oils and chemicals
- > cough syrup bottles and other liquid forms
what type of elastomers can you get and what are some example of these?
natural; made from rubber trees
e.g. latex
synthetic; petrochemicals
e.g. neoprene, nitrile
what are dis/advantages of metal?
\+ impermeable to; light, moisture, gases \+ heat resistant \+opaque \+ imprinted labels \+ light weight vs glass \+ rigid and shock resistant - costs less than less - chemical reactivity - opacity
when are paper and cardboard primarily used?
they are widely used as secondary packaging
what is the dis/advantages?
\+ low cost \+ easy to recycle, non-toxic \+ easy to cut and fold \+ rigid and strong - poor barrier properties - moisture sensitive - required additives for sealing - poor transparency
what are closures used for?
- to provide an effective hermetic seal
- to provide an effective microbiological seal and provide a suitable seal for the product
what must be considered when looking at closures?
- compatibility
- barrier properties
- easy to use
- resistance to processing
- appearance
- additional functionalities
what is the goal of anti-counterfeiting strategies?
to prevent and/or detect counterfeiting
- should act as a deterrent to counterfeiters
1. overt strategies
2. covert strategies
3. forensic markers
what is the overt strategies?
- out in the open \+ product verified by user \+ can be decorative or a deterrent - must be educated - easy to mimic - can increase cost and false assurance - must not be re-usable or recyclable e.g. holograms - colour shifting inks/films
what is the covert strategies?
- hidden \+ simple and low cost \+ easy to add and modify \+ no approval needed - easy to copy - risk of being compromised - higher cost for more secure measures e.g. invisible ink, embedded images, odour, laser coding
what is the forensic markers?
- target; brand ownder \+ highly secure - allows authentication - not detectable under normal conditions - cost - availability may be limited - requires access to specific equipment - increased risk of compromise with wider use e.g. taggants, isotope ratio
what are benefits of glass vial closures?
- extra level of protection given by a dust cap but is not in direct contact with product
- has dust cap, aluminium ring, rubber plug
what are the types of closures you can get?
- screw caps
- seal produced by liner inside cap that presses against container opening; made of plastic and metal - Lug caps
- similar to screw cap only need 1/4 of turn; normal and vacuum pressure closing - crown caps
- crimped closure; used for beverages - child resistant caps
- not left infront of children - roll on
- hermetic seal; can be easily removed or easily re-sealed
- roll-on pilfer proof closures; similar to roll on and tamper evident - tamper-evident closures
- made of white PP or LDPE
- band must be removed fro opening
