Plastics and polymers
- Types
- Advantages
- Disadvantages
- Other possible negative factors
- Stability profiles of injections in plastic
- Additives
- Residues, additives and process aids
- Fabrication process
Thermoplastics
-Soften on heating to a viscous fluid and harded on cooling
-Mould into different shapes and thickness
-Autoclavable (for injection)
+High density polyethylene (HDPE)- poor visual clarity
+Polyvinylchloride (PVC)-Poor flexibility; plasticisers have to be added to form infusion bags
+Polypropylene (PP)- Higher heat resistance than PE
NB- we place additives to plastics to tailor the plastics to what we need for pharmaceutics
Other plastic types
-Polystyrene (PS) \+General purpose and impact modified \+Tablet bottles for dispensing -Polytetrafluoroethylene (PTFE) \+High chemical resistance \+Very expensive \+Coatings or liners -Polyester (PET) \+Increasingly popular for oral liquids \+Inert \+Lower temp resistance
Plastics- advantages
-large material choice
-Broad range of physical and chemical properties
-Large number of fabricaion process
-Range of decorative and printing options
-Numerous design option
+Simple squeezable bottles for eye medications
+Complex valve systems for MDI’s
-Clean process
-Light and robust
Plastics- disadvantages
- Possible extraction of chemical adatives from the plastic- PVC plasticisers
- Interaction with medication- Diazepam absorbed onto PVC
- Absorption of components of the pharmaceutical formulations
- Lightweight
- All plastics p-ermeable to some extenbt to moisture, oxygen and CO2
- Most plastics build up electrostatic charge
- Transmit light unless pigmented
Plastic disadvantages (2)
-Stress cracking
+Caused in LDPE by certain agents- detergents and volatile oils
-Surface crazing
+Fine-scales cracking especially in PS caused by exposure of amorphous plastics to certain chemicals
-Poor printability
+Polyolefins in PE and PP require pre-treatment to enable ink to ‘key’ to surface
-Additives in plastics can migrate to the surface interfering with printing
Plastic disadvantages (3)
-Poor impact resistance with PS and PVC
+Can be improved in conclusion of impact modifiers e.g. rubber
+BUT permeability of plastic increased
-Gamma irradiation of LDPE
+Induces cross-linking and leads to brittlesness
-Negative aspects of plastics for pharmaceutical packaging can be overcome or minimised by suitable design
+Loss of preservatives from by dissolution in LDPE can be reduced by enclosing bottle in PVC blister pack
+PVC impermeable to volatilised preservatives
+Equilibrium of volatile preservative forms in air space between formulation, bottle and pack air space
Stability profiles of injections in plastics (1)
Simulate in use conditions and examine for
-Sensory, chemical and physical changes
-Changes in weight or volume- Plastic permeability
-pH changes
-Effects of light
-Effect of extractables on the injection
+Plasticiser from PVC bags detected in IV fluid
Stability profiles of injections in plastics (2)
-Permeability of gases and solvent vapours through plastic into injection- (overall stability of drug product)
+Cyclohexane- solvent for PVC- extracted from infusion bags
-Absorption of active, bactericides and other components- Drug absorption - diazepam on PVC
Plastic additives
- Polymer
- Residues associated with polymerisation
- Additives used to modify properties
- Process aids
- Knowledge of constituents of plastic essentials; may be extracted from plastic into medication
Residues, additives and process aids
-Residues-
- Monomer (haven’t undergone polymerisation)
- Catlysts
- Accelerators-
Additives- property modifier
- Fillers
- Anti-static agents- minimise static forces
- Anti-oxidants
- Plasticisers- soften plastic that are robust by aligning themselfs between polymer chains
- Pigment /dyes-UV stability
- Whitners/opacifiers
- UV absorbers
- Flame retardants
Process aids
- Solvents
- Release agents
- Emulsifiers
- Lubricants
- Stabilisers
Plastic fabrication process
-Options far greater than glass
+Injection moulding- Molten material injected into mould, to control appiture size
+Blowing moulding- Air used to drive molten plastic into mould
+Thermoforming- vacuum forming
+Extrusion
+Solid phase pressure forming
-Basic moulding operations
+Plastic heated to melt or softern material
+Material shaped in a mould
+Cooling to solidify plastic
New Plastic IV Bags
-Multi-layer, co-extruded polyolefine (Printing on packaging is difficult) based material with inert polyerthylene layer in contact with solution
+This means sterility wont be compramised
-Polypropylene/ polyamide over wrap
Metal and metal containers (1)
-Metals widely used for 10-29 years for rigid containers
+Tablets, capsules, powders and liquids
-Example products
+Collapsible stubes (eye ointment or cream)
+Al tin or tin coated lead
+Manufactured by impact extrusion
+Replaced by plastic
NB- ODT- Al covered container prevents moisture uptake
Metal and metal containers (2)
Modern applications
-Mainly Al and its alloys
-Foils
+Facings for wadded closures
+Pressurised containers- aerosols including MDI’s
+Closures: particularly ROPP (Rolled on Pilfer Proof); Important for security and tamper evidence
Paper and board
-Remains a significant part of 2ndary pharmaceutical packaging- Labels, cartons, bags, information, skrink wrap trays
-Cartons traditionally used for high % of pharmaceutical products
+Increase product display area
+Improve stacking
+Physical protectio - collapsible tubes
+Information- inside and out
+Protection from light
+Compliance= recognition
Films, foils laminates
-End uses
+Sachets, bottle seals, strip packs, blister packs, liners, over-wraps
-Blister packs
+Lid- board, paper, foil, coated film
+Thermoformed tray: PS, PVC, PET, Foil, PE, Or a combo
+Push through systems- lid firmly bounded to the tray
+Peelable system- lid easily pulled back
+Foil blisters or foil overwrap- provides a hermetic pack- excludes virtually exchange of gases between product and surroundings
Closures
-Essential part of primary and secondary pack
-Possible functions
+Totally hermetic seal- fused glass ampoule; No exchange occurs between contents and outside environment
+Microbial seal- Rubber bung with metal over-seal
+Effective seal- Adequate for the product, closure not hermetic nor a total guarantee against entry of bacteria
Rubber Closure
-Ideal properties and requirements
+Good aging properties and oxidation resistance
+Hardness and elasticity should allow neeedle to pass through without blunting
+Puncture should close immediately on withdrawing needle (vials of drugs)
+No change in properties during steralisation
+Impermeable to air and moisture- Penicillin is water sensitive
Closure types (1)
- 2 main types of closure: Physical compression; Heat sealing
1) Plug in: friction or push in (Rubber closure for injections/ampules)
2) Push-Over or ‘Snap-fit’ (e.g. LDPE)- Bead at opening of container CHILD PROOF LIDS
3) Screw cap (Al PE, PP)
4) Rolled on (RO) Al alloy caps - Rolled on pilfer proof (ROPP) Al alloy caps
- Popular for security of export products
- Contact lens solution bottles
Natural rubber composition
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Synthetic rubber
4 main types used in pharmaceuticals
1)Butyl Rubber
-Resistant to chemical attack and ageing
-Poor oil and solvent resistance
2) Nitrile rubber
-Good oil and heat resistance
-Major absorption of bactericides
-Leaching of extratives is high
3)Chloroprene rubber
-Resistant to oxidation and oils
-Low water permeability
4)Silicone rubber
-Heat resistant
-Low water permeability
-Expensive
NB More resistant to high temperature and ageing than natural rubber and latex free BUT more expensive
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powders- lec 126
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Pre-formulation Reformulation Of Powders36
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Powders-Lec 215
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Powders- Lec 3+435
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tabletting56
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RE-formulation7
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Overview of the drug development process20
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Solid state properties26
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Fill weight calcollations4
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Tableting 245
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Kinetics31
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Packaging19
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Packaging 230
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Assessment of pharma products- thermal analysis16
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Clinical trials19
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Regulatory affairs in the pharmaceutical industry19
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Kinetics 26
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Kinetic equations14
