Packaging Flashcards
Economical means of providing presentation, protection, identification/information, containment, convenience and compliance for a product during storage, carriage, display and use until such time as the product is used or administered
Packaging
Packaging is the economical means of providing __________, _________, ________, _________, ________, and _______ for a product during storage, carriage, display and use until such time as the product is used or administered
presentation, protection, identification/information, containment, convenience and compliance
Packaging is the economical means of providing presentation, protection, identification/information, containment, convenience and compliance for a product during _________, ___________, ________ and _______ until such time as the product is used or administered
storage, carriage, display and use
Packaging is the __________ means of providing presentation, protection, identification/information, containment, convenience and compliance for a product during storage, carriage, display and use until such time as the product is used or administered
economical
Role of the Pack & Packaging
-needs emphasis
-must be economical
-must provide protection
-must provide acceptable presentation
-must contribute in terms of convenience and compliance
Packaging needs ____________ as the shelf life of all pharmaceutical products, irrespective of whether they are ethicals, semi-ethicals, or properietaries , is largely dependent on certain functions of the pack
emphasis
T/F: the shelf life of all pharmaceutical products, irrespective of whether they are ethicals, semi-ethicals, or properietaries , is largely dependent on certain functions of the pack
True
Packaging must be __________ and therefore contribute to overall profitability
economical
Packaging must provide protection against ______, __________, ______ and __________
climatic, biological, physical and chemical hazards
Packaging must provide an acceptable ____________ which will contribute to or enhance product confidence while at the same time maintaining adequate identification and information
presentation
Packaging must contribute in terms of convenience and __________
compliance
Shock or impact damage
Compression
Vibration
Abrasion
Puncture or piercing
Mechanical/Physical damages or hazards
Implies rough handling, where rapid deceleration occurs (drops, impacts
Shock/Impact damage
Shock can normally be reduced or overcome by various forms of ___________, _____________ more careful handling, etc
cushioning, restriction of movement,
_____________ can normally be reduced or overcome by various forms of cushioning, restriction of movement, more careful handling, etc
Shock
It should be noted that damage can occur to the pack or packaging material before it reaches the stage of a packed product
Shock/Impact damage
Top pressure or loading can distort and crush a pack and damage the product inside
Compression
Crushing of a carton can make a product unsealable even though no damage has occurred to the contents
Compression
Most likely to occur during stacking in the warehouse or in transit, where vibration adds a further hazard, compression of the pack can occur in other situation (i.e capping on a production line, when being carried home by the user, etc)
Compression
t/f: vibration adds a further hazard
true
Crushing of a carton can make a product _________ even though no damage has occurred to the contents
unsealable
components of product may separate, screw caps may loosen, labels or decoration may abrade, etc
Vibration
two variables of vibrations
frequency and amplitude
this results from both regular and irregular forms of vibration
Abrasion
Although Abrasion is from both regular and irregular vibration, it is listed separately because
visual appearance of the product or pack can be affected
rectangular bottle in a carton will move up and down and from side to side
Abrasion
A round bottle in the same circumstances will suffer from additional possibility of rotation
Abrasion
Many materials can suffer penetration from sharp objects
Puncture or Piercing
t/f: Puncture or Piercing can happen at any stage from basic material supply to the finished pack
T
reduce the risks of puncture or piercing
Adequate cushioning and/or resistance
Poor control of forklift trucks is a
puncture hazard
Moisture
Temperature
Pressure
Light
Atmospheric gases
Solid airborne contamination (particulates)
Climatic or environmental hazards
Liquid or water vapor may cause physical changes (eg dulling, softening, hardening, etc) or chemical change (hydrolysis, effervescence, et
Moisture
Also act as carrier for other contaminants
Moisture
T/F: Certain materials (including all plastics) are to some degree permeable to moisture
True
T/F: even screw closures which appear to make a good seal are likely to permit some passage of moisture depending on the sealing medium , the torque, the evenness and shape of the sealing surface, the aperture size and circumferential area of the container
True
T/F: Must be emphasized that only moisture loss may be critical to some products
F: either moisture loss or moisture gain may be critical to some products
produce a shower effect if the temperature is lowered sufficiently to reach dew point
High temperature coupled with high RH
generally represent an acceleration effect occasions can be found where deterioration increases at lower temperatures
Higher temperatures
T/F: Extremes of temperature (hot) or cycling temperature can cause deterioration to product and/or pack
false - hot and cold
Contamination from liquid moisture can then encourage mould and bacterial growth
Temperature
Air pressure differentials are frequently seen as a danger for materials sent by air using ______________ aircraft
unpressurized
Pressurized aircraft are pressurized to the equivalent to about 3000 m above sea level, hence there is a ________ bar differential compared to take off
-0.25
T/F: Goods filled in factories at sea level and sent to mountainous areas, or vice versa, will suffer from similar patterns (of pressure change)
T
T/F: goods packed in johannesburg, south africa, at 2000 m and then sent to durban at sea level will be exposed both a positive pressure and probably to a temperature change
T
Consists of wavelength from the UV zone through the visible to infrared
Light
a potential source of photochemical change, such changes may not always be visible
UV
may reduce penetration or filter out selected wavelength.
tin plate, foil, etc opacity and/or color
may also restrict light rays entering the pack
Additional use of UV absorbers in plastics
Include oxygen, carbon dioxide, nitrogen and any other airborne gases
Atmospheric Gases
Oxygen leading to oxidation is the ________
more obvious hazard
can cause a pH shift and/or lead to precipitation of some products
Carbon dioxide
Permeation of the common gases through plastic is typically in the ratio of
1:4:20 (nitrogen, oxygen and carbon dioxide)
most permeable (gas)
carbon dioxide
T/F: Odorous gases or volatile ingredients associated with perfumes, flavors and product formulations may also pass into or out of a pack
T
If a volatile ingredient is lost from a flavor, an ___________ _________ or ______ may result
unpleasant odor or taste
Particulates
May be carried by or in the atmosphere
Solid Airborne Contamination
most plastic contamination may be ______________ (increased/decreased) by electrostatic attraction under dry conditions
increased
particulates are drawn from the atmosphere by ___________
electrical charges
In the case of most plastic contamination may be increased by ______________ under dry conditions whereby particulates are drawn from the atmosphere by __________
electrostatic attraction; electrical charges
Microbiological
Other forms of infestation
Pilferage and adulteration risks
Biological Hazards
Microbiological
Other forms of infestation
Pilferage and adulteration risks
Biological Hazards
Packaging materials must be reasonably clean initially, and when put together to form a finished pack, restrict any further contamination as much as possible
Microbiological
In the case of sterile products the pack and its closure must maintain a
_______________ effective seal against microbiological ingress (i.e bacteria, molds, yeasts
100%
Ingress of yeasts is critical with ____________ based products
sugar
Molds will grow on ________ based materials, i.e. paper and board, if these are kept under __________ conditions
cellulose; humid
T/F: , other sources of infestation that can contaminate pharmaceutical products include attack by insects, termites, vermin, rodents, or any other bird-or animal-contaminating source
T
More likely to happen under poorly controlled condition of hygiene and housekeeping
Other Forms of Infestation
widely used for pharmaceutical products as a means of increasing and maintaining user confidence in the product and pack
Security seals
used to indicate whether any product had been removed or replaced, rather than as a means of protecting against deliberate adulteration
Various seal
T/F: Pilferage being a human failing is broadly another biological hazard
T
Organoleptic changes
Increase in toxicity/irritancy
Degradation
Loss or gain of microbial effectiveness
Precipitation
Haze
Turbidity
Color changes
pH shifts
Chemical Hazards
Stages in the Development of a Pack-Product Combination
Preformulation
Product formulation
Consideration of container materials
Pack feasibility tests
Formal stability tests
Ongoing stability
complaints
Stage where a product is tested in a range of possible packs, usually over a range of conditions from -20 C to 45 C, together with some cycling conditions covering a temperature-humidity range
Pack Feasibility Tests
are mandatory for plastics used for injectables and ophthalmic products
Extractive tests
Feasibility tests usually extend over 1-12 months, with ________ months normally being the minimum before a decision to proceed with a certain pack is taken
3-6
Once sufficient confidence has been generated in the pack-product combination,________________, on which the shelf life will be based, can proceed
formal stability tests
Test conditions have been specified by the ________________- and adopted by the major regulatory bodies in Europe, USA, Japan and Asia
International Conference on Harmonization
for long term stability
25C and 60%
for accelerated stability
40 C and 75% RH
3 large scale batches of product in each pack variant are stored at 25C and 60% RH for long term stability purposes and at 40 C and 75% RH for accelerated stability, and sampled over a period of _______ years
5
Data generated are sent to the _______
regulatory authorities
This consists of repeated stability on random batches from production in order to confirm that the shelf life does not change
Ongoing stability
Final means of monitoring the success of the product and pack
Complaints
T/F: Complaints are somewhat similar to the monitoring and recording of adverse reactions in that it is a safeguard to both the company producing the drug and the person receiving it
T
Factors Influencing Choice of Pack
Product
The market
The distribution system
Manufacturing facilities
Disadvantages of glass
friability and heavy weights
surface treated soda glass
neutral (type 1
soda or alkali glass
(types III and IV).
equipment used to shape glass cane
tubular container
glasses can be converted by
pressing, blowing into a mold, or the shaping of glass cane
Silica composition
Type 1 - 66-74
Type 2 - 66-75
Lime composition
(I) 1-5
(II) 6-12
Soda compostiion
(I) 7-10
(II) 12.5-19
Alumina composition
(I) 4-10
(II) 1-7
Boric oxide composition
(I) 9-11
In what type of glass is the alkaline element is largely eliminated by the use of boric acid oxide to neutralize the oxides of potassium and sodium
type I
t/f: Neutral glass has a higher melt temperature (around 1750 C) and narrower working temperature range
True
T/F: Neutral glass has a higher melt temperature (around 1750 C) and narrower working temperature range, which, together with higher cost of boric oxide and lesser likelihood of imperfections, usually a cost of 2-3x that of soda glass for containers ma. de by blow molding process
F: greater likelihood of imperfections
made by treating the hot surface of type III glass with sulfur dioxide, ammonium sulfate or, in some countries, ammonium chloride
Surface treated glass
Surface treated glass type
Type II
invariably leaves a hazy surface bloom and so washing is essential prior to use
sulfurating or sulphating
neutralizes some of the surface alkali radicals, producing a more surface
sulfurating or sulphating,
Most widely used material where extraction of alkali metal ions is not critical to the product; Soda Glass
Type III
Has the same composition to type III, but it cannot be guaranteed to have the same quality
Type IV
_________ mainly used in metal containers
tin plate or aluminum
widely used for collapsible tubes
Light, flexible gauges of metal (aluminum, tin and tin coated lead)
widely used as foil in combination with other support or heat sealing polymer films
Thin gauges of aluminum
The production of collapsible tubes made by a process known as
impact extrusions
Tubes with elongated nozzles and a controlled orifice size are used for
eye ointments
T/:F Nearly all caps on metal tubes are wadless, being plastic and moulded in polyethylene and polypropylene
True
Plastics now used are related mainly to the
thermoplastic resins
Most economic four are
polyethylene
polyvinyl chloride
polypropylene
polystyrene
Disadvantages of Using Plastics
- Possilbe extraction, interaction, adsorption, absorption, lightness and poor physical stability
- All are permeable to some degree to moisture, oxygen, carbon dioxide etc
- Most exhibit electrostatic attraction, allow penetration of light rays unless pigmentted black etc
- stress cracking, panelling or cravitations, crazing, poor key print and poor impact resistance
Phenomenon related to low density polythene and wetting agents, detergents and some volatile oils
Stress Cracking
Whereby a container shows inward distortion or partial collapse owing to absorption of gases from the headspace, absorption causing swelling of the plastic, or dimpling following a steam autoclaving operations
Panelling or Cavitation
Surface reticulation which can occur particularly with polystyrene and certain chemical substances
Crazing
first causes crazing, which ultimately reaches a state of total embrittlement and disintegration
isopropyl myristate
Certain plastic, such as the polyolefins, need penetrating before ink will key
Poor Key of Print
have poor impact resistance
polystyrene and PVC
how to improve plastic’s impact resistance
the inclusion of impact modifiers; rubebr for polysterine and methyl methacrylate butadiene for pvc
Materials that found in a plastic materials fall into 4 categories :
- polymer
- residues associated with the polymerization process
- additives (those constituents added to modify the plastic in a specific way) - any processing aids (which are used to assist any part of the process)
Injection moulding, injection and extrusion blow moulding, injection stretch and extrusion stretch blow moulding, thermoforming, scrapless forming process, reaction injection molding and solid phase pressure forming, all of which relate mainly to thermoplastic resins
Fabrication of Plastics
Covers labels, cartons, bags, outer, trays for shrink wraps, layer boards on pallets etc
Paper & Board
are used for high % of pharmaceutical products
Cartons
increasing display area, providing better stacking for display of stock items, coating of leaflets, physical protection.
Cartons
used as an overwrapping material either for individual cartons or to collate a number of cartons
Regenerated cellulose film (Cellophane and Rayophane)
t/f: paper, even when waxed, has relatively poor protective properties against moistures, both paper and board
t
Supportive, barrier, heat seal and decorative
Films, Foils and Laminates
Sachets, diaphragm seals for bottles, strip packs, blister packs, liners for boxes, either attached or loose bag in box systems and bags
Films, Foils and Laminates
appear to offer reasonable degree of child resistance, particularly if the materials are opaque
Both blister and strip packs
T/F: rubbers are made from either natural or synthetic sources
t
T/F: Majority of rubber usage is related to the closure of sterile products
T
offers advantages in terms of resealing, fragmentation and coring ), but is poorer in respect to ageing, multiple autoclaving, extractives, moisture and gas permeation and the absorption of preservative systems.
natural rubber
descriptions for the means by which particles are created when a needle is passed through a rubber
coring
improve reseability, fragmentation and coring
natural rubber
contains vulcanizing agents (many of which are sulfur based), accelerators, fillers, activators, pigments, anti-oxidants, lubricants, softeners or waxes
rubber formulations
Main types of rubber
natural rubber, neoprene, nitrile, butyl-, chlorobutyl-, bromobutyl and silicone
most expensive and inert, is readily permeable to moisture, gases and absorbent to certain preservatives
Silicone
are likely contain more additives than plastics, therefore tested by basically similar extractives and product contact procedures before they are used for injectable or IV products
Rubber
are also found in aerosols and metered dose pump system
Rubber gaskets
Providing a seal frequently depends on the marriage of a hard material with a softer, more resilient one, so that the former makes a physical impression on the latter
Closures
To provide a totally hermetic seal
To provide an effective microbiological seal
To provide an effective seal which is acceptable to the product
Functions of a closure
General consideration for closure
-must be resistant and compatible with the product
-readily openable and resealed if of a reclosable
-be capable of high speed application
-decoarative
-offer additional functitons
-prevent limit exchange with outside temp
Physical compression systems
Screw caps
Plug in
Push over
– inmetal or plastic; prethreated or rolled on, with or without a wadding system
Screw caps
friction push in fit
Plug in
where a flanged or raised ring portion is pressed over a bead or lip
Push over
Placing a dessicant in a pack stored under high RH and detecting any moisture gain
Determination of closure efficiency
Putting liquid inside the pack, storing at high temperature and low RH, and then detecting any moisture loss as a reduction in weight
Determination of closure efficiency
Holding the empty pack under water, applying a vacuum and observing for leakage or liquid ingress. Adding a dye and wetting agent to the water may assist the defection of leaks
Determination of closure efficiency
Putting liquid in the pack, inverting and applying a vacuum. A poor seal is detected by liquid seeping or leaking out
Determination of closure efficiency
Checking that cap-removal torque is satisfactory
Determination of closure efficiency
Checking on compression ring seal in cap liner when the system contains a liner or lining compound
Determination of closure efficiency
the length of time that temperature and pressure are applied
dwell
T/F: in heat seals, Factors (temp. pressure, dwell, cooling) have to be controlled
T
Main heat sealants include
polyethylene, wax coating, PVdC, Surlyn ionomer, selected vinyl based products and certain types of modified polypropylene
Other Sealing Methods
Ultrasonics, high fequency welding, hot air welding and by other heat sources (flame, infrared, induction, etc)
products packed on production lines include such items as unit and multidose packs, closable and non-reclosable packs, sterile products produced aseptically or by terminal sterilization, or non-sterile products with or without degree of microbiological control, preformed containers which have to be filled and sealed
Filling
T/F: filling may be fauirly conventional and involve unscrambling, cleaning, filling, closuring, labeling, cartoning, outerization and finally palletization, or be selective to a specialist operation
t
printing, batch coding, expiry dating and incorporation of administration aids
aditional operations for filling
labor, planned maintenance, staff training, online quality control, facilities for batch coding and expiry dating where relevant, constant delivery of an adequate supply of materials to the agreed specification on to the line, and removal of the finished product from the line
Organization of packaging lines
Defined procedures for cleaning, start up and close down of the line, plus full documentation on both procedures and materials to be handled and environmental control, which all form part of CGMP
Organization of packaging lines
tablets, capsules, are counted by
resolving disc, slat counter, breaking a beam of light
volume using an auger or filling cup, or by weight using a bulk feed plus trickle top up
Powder or granular products
filled volumetrically either by a piston type filler or gravity feed
Cream and ointment type products
filled by piston filler, volume cup method using a pressure or gravity feed
Liquid products
used variety of materials (metal, glass coated glass or plastic as containers and combinations of metal, plastic, and rubber for the valve). Comes into existence once it has been filled with a product and pressurized with a propellant
Aerosols
Aerosols are pressurized with a
propellant
divided into small volume, large volume injections and dialysis solution. Glass, plastic, rubber
Parenterals
