Containers Flashcards
What does the USP classify containers according to?
Their ability to protect contents from external conditions
What are some basic characteristics of a good container?
Inert material Withstand temperature and mechanical use Protection from radiation and microbiological contamination Transparent Inexpensive Space for label Facilitate storage
What is a USP container?
Holds article, may or may not be in direct contact with it
What is an immediate container?
Direct contact with article at all times
What is a well-closed container?
Protects contents from extraneous solids and the loss of article under ordinary handling, shipping, storage, distribution
What is a tight container?
Protects contents from contamination by extraneous liquids, solids, vapours, and from loss from efflorescence, deliquescence, evaporation
What is deliquescence?
To dissolve and become liquid by absorbing moisture from air
What is efflorescence?
Loss of water of crystallization from hydrated/solvated salt due to exposure to air
What is a hermetic container?
Impervious to air/gas under ordinary conditions (e.g., single use or multiple-dose containers)
Can withdraw liquid without changing its quality, purity, strength
What is a unit-dose container
Single-unit contained for articles intended for administration by route other than parenteral as a single dose, direct from container
Do single unit containers need to be child resistant?
Yes (including blister packs) but not in hospitals
What is the USP definition for cold?
Any temperature not exceeding 8C
Fridge: 2-8C
Freezer: -10 to -25C
What is the USP definition for cool?
8-15C
May store in fridge unless otherwise specified
What is the USP definition for room temperature?
20-25C is typical room temperature, but can be as wide as 15-30C
What is USP definition for warm?
30-40C
What is USP definition for excessive heat?
> 40C
How do you test for chemical resistance in borosilicate glass, treated soda-lime glass, and soda-lime glass?
Borosilicate = powdered glass
Treated soda-lime = water attack
Soda-lime = powdered glass
What are some test methods to test plastic containers?
IR, DSC (differential scanning calorimetry), biological tests, physicochemical tests (air permeability, leaching into plastic, surface adsorption, light transmission, plasticizer)
What are biological tests? What do they measure? What are the different grades?
Measure the biological reactivity of mammalian cell cultures following contact with elastomeric plastics and other polymeric materials
Grade 0 = No reactivity (no cell lysis)
Grade 1 = Slight reactivity (occasional lysed cells)
Grade 2 = Mild reactivity (no extensive cell lysis, empty areas between cells)
Grade 3 = Moderate reactivity (not more than 70% of cells lysed)
Grade 4 = Nearly complete destruction of cell layers
In tight containers, moisture permeability should not exceed what?
> 100mg/day/L in one container, none should exceed 200mg/day/L
In well-closed containers, moisture permeability should not exceed what?
> 2000mg/day/L in one container, none should exceed >3000mg/day/L
What must pharmacist include on blister packs/customized medication package? What container class must these packs comply with?
Date/time contents are to be taken Patient package insert OR single, overall medication educational insert Container must comply with class B single-unit container and should not be re-closable/show signs of being tampered with
What are the four classes of containers (A-D)?
Class A: Not more than 1 of 10 containers tested exceeds 0.5mg/day in moisture permeation rates and none exceeds 1mg/day
Class B: Not exceeding 5mg/day and none exceeding >10mg/day
Class C: Not exceeding 20mg/day and none exceeding >40mg/day
Class D: Containers tested meet none of the moisture permeation requirements
What must the label for custom patient medication packages include?
Name Serial number Name, strength, description, quantity of drugs Directions and cautionary statements Storage Prescriber name BUD Pharmacy contact info
What must record keeping show for customized patient medication packages?
Name of patient Serial number Lot number/manufacturer info for each drug Info on pack design Date of preparation, BUD Label instructions Name and initials of pharmacist
What is an advantage of using glass containers?
Relatively chemically inert
What are reactions with glass influenced by?
Type and agitation of solution Washing procedures Thermal history Current temperature Glass composition Storage time
What do alkali solutions do to glass?
Cause glass flakes to separate from walls over time, yields soluble mineral substances into aqueous injections
Precipitation: Alkaloids, polypeptides
Decreased stability: Alkaloids, polypeptides
What is Type I glass?
High Hydrolytic Resistance to Boro-Silicate Glass
Neutral or borosilicate glass (increase boron and aluminum oxides), injectable preparations, may be re-used
What is Type II Glass?
Lime-soda glass
High hydrolytic resistance
Treat surface with moist SO2 at 500C
Injectable preparation is not for re-use
What is Type III Glass?
Lime-soda glass
Moderate hydrolytic resistance
Packaging of liquid preparations not in aqueous vehicle and for powders to be re-constituted immediately before use
What are some quality control tests for glass?
Light transmission
Chemical resistance
Powdered glass test
Water attack at 121C
General traits of soda lime glass (type III)
Soft, not very chemically resistant
Thermal shock
Anhydrous, dry content
General traits of surface-treated glasses (type II)
Treat at 500C and with SO2
General traits of borosilicate glass (type I)
Boron and aluminum oxide
Better chemical resistance and shock resistant
Higher price
Higher melting point
What are ampoules?
Thin walled, glass/polyethylene/polypropylene, sealed by fusion; single use
What are vials?
Thin to medium walled; rubber stopper; single/multiple use
Pre-filled syringes and cartridges
What are 8 general properties of plastics?
1) Synthetic polymers of high MW
2) Sensitive to heat, may melt/soften below 100C, some can be autoclaved (e.g., nylon)
3) Lightweight, easy to handle, cheap transport
4) Almost as strong as metal, thinner walls than glass
5) Poor heat conductors (disadvantage if container needs heat sterilization)
6) Resistant to organic chemicals but attacked by organic substances (e.g., solvents, oils)
7) Contain antioxidants, lubricants, plasticizers, stabilizers (substances may leach out and decrease stability of medication)
8) Some are permeable to water, gases (oxygen, carbon dioxide)
What are thermoplastics?
Plastics that can be repeatedly softened by heating and hardened by cooling through a temperature range
Hardening when cooled is influence by degree of cross-linking or intermolecular attraction between long chain molecules
What are thermosetting plastics?
Plastic that, when cured by application of heat/chemicals, turns into a substantially infusible end product
When heated, they may become flexible but do not become fluid and their shape is retained right up to temperature of decomposition
Hard and brittle at room temperature (e.g., phenol, urea, melamine formaldehydes)
What is high density polyethylene? What plastics number is it?
Right, cheap, easy to form, resistant to breakage plastic
Makes milk bottles, water and juice bottles, bleach, etc.
Cloudy white, or light passes through
Plastic #2
What is low density polyethylene (LDPE)? Does it contain plasticizers? What plastics number is it?
Applications requiring clarity and processing ease
For grocery bags
NO PLASTICIZERS
Plastic #4
What is polyethylene terephthalate (PETE)? What plastics number is it?
Used for clothing, plastic films, plastic bottles
30% of plastic bottle market
Clear, tough, resists carbon dioxide permeation
Plastic #1
What is polyvinyl chloride used for (PVC)? What plastics number is it?
Water pipes, LP records, vinyl car tops Clear, 30% PLASTICIZER Permeable to water and oxygen Blood collection bags Not useful for radiation sterilization Plastic #3
What is polypropylene (PP)? What plastics number is it
Clear, brittle at low temperatures, can be autoclaved
NO PLASTICIZERS
Rope fibres, indoor-outdoor carpeting, plastics
Plastic #5
What is polystyrene? What plastics number is it?
Right plastics, polystyrene foams
Plastics #6
What are other plastics? What number are they?
Plastics #7
All other plastics, including those made from >1 polymer
What is polyamide?
Good strength, wear resistance, barrier properties, mechinability
Surface and stiffness are often improved using glass fibre reinforcement
Absorbs water, makes it softer
Need UV stabilizers for outdoor applications
Transparent and opal white plastics
What is polymethylacrylate?
Plexiglass
Softens at 100C
Aseptic screens, contact lenses, heart and lung machines
What is polydimethylsiloxane silastic?
Closures, tubes, diaphragms, implants, contacts
Less interactions
What is polytetrafluoroethylene (teflon)?
Heat resistant up to 200C
Semi-rigid
Slippery and non-wettable
What is polymethylpentene?
High temperature resistance
Expensive
What is polycarbonate?
High temperature resistance
Brittle
Compatible with ethyleneoxide
What are polyesters?
Beverage bottles
Co-polymers = saran wrap (PE + latex) and PVC (aluminum foil)
What is rubber?
Natural polymeric material with many additives
Closures
Treat with silicone derivatives to decrease interactions
Contains particulate and microbial contaminants
Many interactions
Three types: butyl, nitrile, chloroprene
What are some good qualities to have in closures?
1) Good ageing qualities
2) Satisfactory hardness and elasticity
3) Resistance to sterilization conditions
4) Impermeable to moisture and air
5) Negligible release of undesirable substances
6) Negligible extraction of injectable ingredients
What is container leaching? What increases leaching?
Leaching is release of components of container into contents
Increased by increasing temperature, agitation, polymer additives
Do the following factors increase or decrease diffusion through polymers? Increased polymer MW Increased degree of cross-linking Diluents and plasticizers Fillers Increased crystallinity Increased drug size Increased hydrophilicity
Increased polymer MW - decreases Increased degree of cross-linking - decreases Diluents and plasticizers - increases Fillers - decreases Increased crystallinity - decreases Increased drug size - decreases Increased hydrophilicity - decreases
What is the most common cause of moisture entering a container?
Imperfections in seal
Also, the environment during packaging, product, transmission, additional internal packaging
What are some examples of dessicants?
Activated clays/zeolites (mined and processed - fair absorption capacity at low RH, inexpensive) Silica gel (high capacity = >40% RH; low capacity = 32C) Molecular sieve Calcium oxide (colour change) Preformed shapes Cards with colour indicators Sachets in Tyvek Cannister/cartridges in HDPE Cap built into lid
What are some examples of sorbents?
Activated carbon (adsorbs organic compounds, can be combined with dessicants and oxygen absorbers, non-toxic) Ferrous-based materials (absorb oxygen, irreversible reaction)
Containers must be protected from what four types of hazards?
Mechanical
Biological
Environmental
Chemical
