D&M Pharmaceutical Packaging

1. How is packDrugs can partition out of a medicine and into packaging, aging associated such as an infusion bag or catheter as they can change with drug loss? pH for example. 2. What does the pH partition hypothesis suggest? What are its limitations? The pH partition hypothesis states that the unionised form is preferentially absorbed through the lipid membrane to reach the blood stream. However, limitations include surface area, solubility, and localised pH. 3. What are some examples of specific drugs that have problems associated with packaging? There have been problems with GTN and diazepam as they are affected by a small change in pH. There is a greater loss of warfarin at pH 4.9 than pH 5.6 as it will stick to the packaging because it becomes more ionised. 4. What is GTN in- GTN is incompatible with polyvinylchloride and severe compatible and losses (up to 50%) of glyceryl trinitrate may occur if this compatible with? material is used, resulting in a reduction of delivered dose and efficacy. Contact of the solution with polyvinylchloride bags should be avoided. Polyurethane also induces a loss of the active ingredient. GTN is compatible with glass infusion sets and with rigid infusion packs made of polyethylene. It may also be infused slowly using a syringe pump with a glass or plastic syringe. 5. What does a packaging provide a product with? Presentation, protection, identification/information, containment, patient convenience and compliance. This should be during storage, carriage, display, and use until such time as the product is used or administered. 6. Why (chemical- To ensure stability and protect from deterioration. A label ly) are medicinal statement should not be used to compensate for inadeproducts pack- quate packaging. aged into containers? 1 / 13 7. What is primary packaging? What are some examples? Primary (immediate) packaging components are in direct contact with the dosage form. Examples include blister packs, strip packs, sachets, bottles, ampoules, vials, bags, tubes and syringes. 8. What is secondary packaging? Secondary packaging components are not in direct contact with the dosage form. It contains the primary pack. 9. What is the purpose of secondary packaging? - Extra protection - Product information and instructions - Inclusion of other items, such as measuring devices or information leaflets. - Security - Ease of handling/transport - Appearance 10. What is the importance of packaging (both primary and secondary)? - Protection against adverse external influences that can alter the properties of the product, such as light, moisture, oxygen. - Protection against biological/microbial contamination. - Protection against physical damage, adulteration. - Correct information and identification of the product. - Tamper evident - child resistance and anti-counterfeiting, form of security. 11. What are the two - Containment (prevent leakage, diffusion/permeation, main functions of strong enough to hold contents during handling) packaging? - Protection 12. What are the different hazards that packaging can protect drug products from? What is the one hazard associated with packaging? - Chemical (associated with packaging) - Mechanical - Environmental - Biological - Access 2 / 13 13. What chemical hazards are associated with packaging? - Absorption (molecules are drawn into the bulk of the phase) - Adsorption (molecules adhere to the surface of the phase) - Evaporation - Extraction 14. What mechanical hazards can packaging prevent? - Shock/impact - Vibrations - Puncture - Abrasion - Compression 15. What environmental hazards can packaging prevent? - Temperature - Moisture - Atmospheric gas - Radiation 16. What biological hazards can packaging prevent? - Microbial - Infestation - Adulteration - Piliferage 17. What access hazards can packaging cause/prevent? - Advantaged/disadvantaged people - Controlled dosage pack - Young - Blind - Elderly - Arthritic. 18. In addition to preventing hazards, what are the additional qualities of packaging required? - Preserve the physical properties of all dosage forms and protect them against damage or breakage. - Not alter the identity of the product. - Preserve the characteristic properties of the product to comply with specifications. - Must protect product against undesirable or adultering chemical, biological or physical entities. 19. - Container - Closure 3 / 13 What are the - Overseal packaging com- - Labelling ponents? - Leaflets - Associated components (e.g. dosing spoons or measuring cups). - External packaging (e.g. cartons, shrink wrap, cardboard box). 20. What are the ma- - Plastics and plastic films terials involved in - Glass packaging? - Metal (aluminium foil, tinplate) - Laminates (paper/foil) - Paper and paper board - Cardboard - Rubber - Pressurised containers 21. What are the dif- - Product drivers ferent influences - Patient drivers for choice of - Marketing drivers packaging? 22. What are the different product drivers that influence the choice of packaging? - Nature of product - Degree of protection required - Compatibility with medication - Required shelf life - Form of dose - Method and site of administration 23. What are the pa- Type of patient and customer convenience. tient drivers influencing choice of packaging? 24. What are the marketing drivers influencing choice of packaging? - Capacity of packaging needed. - Presentation - Method of distribution - Cost 25. Bottles, jars, blisters, strips, tubs. 4 / 13 What are solid dosage forms usually packaged in? 26. What are oral liquids usually packaged in? bottles, unit dose pack 27. What are ophDropper bottles, squeeze and spray packs, unit and multhalmic, aurtidose packs. al and nasal products usually packaged in? 28. What are throat products packaged in? Bottles, pumps, aerosol sprays. 29. What are parbottles, plastic bags, ampoules, vials, pre-filled syringes. enteral products usually packaged in? 30. What are ointJars, pots, tubs, collapsible tubes. ments, creams, and pastes usually packaged in? 31. What are pulAerosol/powder devices. monary products usually packaged in? 32. What are the advantages of using glass as a packaging material? - Almost inert to aqueous solutions, solvents, oils and most medicinal products. - Impermeable to gases and vapours, and impervious to air and moisture. - Inexpensive. - Can form different shapes and accept a variety of clo5 / 13 sures/dispensing devices. - Easily filled, cleaned and sterilised. - Transparent to easily inspect contents. - Can be coloured for appearance and to reduce passage of light (amber). 33. What are the disadvantages of using glass as a packaging material? - High density/weights means increased transport costs and less convenient to carry. - Fragile and easily broken. - Some types of glass release alkali into contents. - May develop contamination from particles during storage due to erosion of surface (because of sterilisation by autoclaving alkaline solutions such as sodium citrate). 34. What are the typ- silica (e.g. sand), calcium oxide (from limestone), aluical constituents minium oxide (from bauxite) and various metals oxide (to of glass? create coloured bottle). 35. What are the types of glass? - Type I (neutral) - Type II (surface treated soda-lime glass) Type III (soda/alkaline) 36. What is type I glass? - Boro-silicate glass (boron oxide added to glass). - High hydrolytic resistance, most inert glass, lowest coefficient of thermal expansion, and shows the least amount of leaching of glass components. - Preferred for aqueous medicines where a pH shift to alkaline is unacceptable. Does not leach alkaline material, withstands change in pH as its neutral. - Widely used for vials/ampoules - fluids for injection. Can be autoclaved and be sterilied (as won't expand in heat). - Expensive. 37. What is type II glass? - High hydrolytic resistance, interior surfaces treated at a high temperature and sulphur dioxide to eat away the alkali on or near the glass surfaces. - Lower melting point and less costly than Type I. - Used for aqueous preparations other than parenteral, due to lower melting point. 6 / 13 38. What is type III glass? - Untreated soda-lime glass exposure of surface to acidic fumes at 500 degrees which neutralises the surface, making it alkali-free. - Offers only moderate resistance to leaching. - Used for typical dispensary metric medicine bottle. 39. What are the advantages of using plastic as a packaging material? - Flexible and not easily broken. - Release few particles into product. - Low density. - Can be heat sealed. - Easily moulded into various shapes. - Suitable for primary container, closure, and as secondary packaging. - No corrosion problems - Resistant to attack by bacteria, moulds, and yeasts. - Cheap. 40. What are the disadvantages of using plastic as a packaging material? - Not as chemically inert as glass. - Swollen by some solvents and chemicals. - Some undergo stress cracking and distortion from contact with some chemicals. - Not as impermeable to gas and vapour as glass. - May possess electrostatic charge which will attract particles. - Additives in the plastic can leach into product. - Substances may be taken up from the product. - Only semi-rigid and distort under load. 41. What are the two thermoplastics and thermosets classes of plastics? 42. What are thermosetting plastics? What are they used for? Soften only one (during heating in moulding process) and are then irreversibly hardened (cured). Used for making screw caps for glass and metal containers. 43. What are thermo- Have property of softening repeatedly on heating and plastics? hardening again when cooled. 7 / 13 44. What are some Principal polymers are polyethylene (low density, linear examples of ther- low density, high density), polyvinyl chloride, polypropymoplastics? lene, and polystyrene. 45. What is low den- Flexible eye drop bottles. sity polyethylene used for in packaging? 46. What is linear low Heat sealable containers. density polyethylene used for in packaging? 47. What is high den- Solid dosage form container. sity polyethylene used for in packaging? 48. What is polypropylene used for in packaging? Container closures, IV solution bottles. 49. What is polyvinylchloride used for in packaging? IV bags, laminate for blister packs. 50. What is polyContainers for oils, creams, and solid dosage forms. styrene used for in packaging? 51. What are two ex- - Unit dose packaging amples of special - Device packaging packaging? 52. What is good about unit dose packaging? safer medication, more practical for patients, improved compliance, useful for less stable products. 8 / 13 53. What is involved packaging with the aid of an administration device, with device pack- user-friendly, improves compliance, easier administration aging? by means of devices. 54. What is the com- - Polymers position of plas- - Additives which could leach into formulation (plasticiser tics? increasing flexibility, resins, stabilisers, lubricants, anti-static agents). 55. What can tablets - Multiple-unit container closure systems. be packaged in? - Blister packaging - Strip packaging 56. How is a multi- high density polyethylene (HDPE) bottles with polypropyple-unit contain- lene (PP) fine ribbed or child-resistance closures, liners, er closure sys- inner seals, desiccants and fillers. tem created? 57. How is blister blister laminate which is thermoformable (PVC for expackaging creat- ample) or cold-formable film (nylon-AI-PVC) with a foil ed? (aluminium) or paper-foil laminate substrate with a sealing agent. 58. How is strip laminate with aluminium foil packaging created? 59. What are the three materials usually used to package parenteral products? - Glass, rubber, plastic 60. What is the importance of packaging for parenteral products? - Long term protection - Maintains physical and chemical stability - Drug delivery tool by providing more convenient delivery of the drug product (such as syringes or dual chamber 9 / 13 vials). - Better control of drug doses (such as cartridges) 61. What are issues associated with parenteral products packaging? This packaging can be a major source of particulate contamination and can contribute to physical and chemical degradation of the products. Packaging constituents can leach into product or product can be absorbed/adsorbed. 62. What are some examples of packaging systems used for parenteral products? Primary small volume injectable packaging systems include glass sealed ampoules, rubber closed vials, prefilled syringes, cartrdiges and small/large volume bottles made either of glass/plastic. 63. How are aerosols packaged and what is important to consider? - Composes of container and valve. - It is important to consider unit spray content, leakage rate, content uniformity, number of doses, spray pattern, valve delivery, particle size distribution. 64. What are closures? What qualities do they need to have and what are some examples of types of closures? - Primary packaging used to cover/seal container. It must provide an effective seal and exclude external contaminants. - It must allow easy and safe administration - (should be removable, re-closable, pierced with a needle). - Closures can be caps, overseals, lid, stopper, and tamper evident or child-resistant (CRCs). 65. What are child-resistant closures material, designs? - Professional and in some cases legal requirement. - Uses high density polypropylene. - Various liners - Designs include cap-bottle alignment (align arrows Snap-safe), push down and turn cap (Clic-loc), squeeze and turn, squeeze and pull. 66. How do you test child-resistant closure in 200 children ages 42-51 months given 5 minutes to try and open the pack. They are then given a demonstration and a further 5 minutes. It is deemed child-resistant if at least 10 / 13 reclosable pack- 85% cannot open after first 5 minutes and at least 80% ages? after further 5 minutes after demonstration. 67. How do you test child-resistant closure in non-reclosable packages? Testing methods for mechanical properties such as bursting strength, packaging should remain child-resistant for entire product lifetime. The outer pack must be opaque/dark-tinted so unit doses are suitably disguised. 68. How do you test child-resistant closure in adults? 100 adults, 70% female. Half are between 50-59 and half are aged 60-70. The pack passes if 90% of adults can open and re-close the package properly within 1 minute after handing a familiarisation pack, or open and remove one item if non-reclosable. 69. What is tamA tamper evident/resistant package is one having an inper-evident pack- dicator to entry in which, if missing, can reasonably be aging? expected to provide visible evidence to consumers that tampering has occurred. 70. What are some examples of tamper evident closures? - Film wrappers and shrink sealed bands due to heat induction. Transparent, tight fit with a perforated tear strip. - Blister/strip packs - Breakable caps - Tamper-evident liners (inner seals made of paper, foil, plastic films) - Film wrappers/plastic pouches - Tape seals (decorative tamper evident labels) - Aerosol containers - Sealed metal tubes/plastic heat-sealed tubes. 71. At what stages of - Pre-formulation the drug devel- - Product formulation opment pipeline - Materials - Stability tests 11 / 13 is the pack being - On-going stability tests developed? - Complaints 72. How do you choose the appropriate primary pack? - Product characteristics/sensitivity - chemical degradation, photosensitivity, physical degradation, hygroscopicity (absorbs moisture from air), drug release properties, mechanical properties. - Selection of packaging - moisture/light/gas/barrier requirements and chemical properties. 73. What must you consider when choosing packaging and what are the solutions? - Photosensitivity (use opaque/amber container and secondary packaging) - Ingress/loss of moisture vapour (integrity of packaging and seal, stronger) - Leakage (use packaging material and adequative closure system - induction seal) - Leaching/absorption/adsorption/reactivity (use a packaging material that coats) 74. How can the primary packaging containers impact integrity of the product? - Allow seepage/leakage of product - Allow ingress of substances - Release substances into product, inducing drug degradation. - React with product - Absorb or adsorb substances from product, reducing drug potency. 75. What hazards can be encountered with the drug product? (regardless of packaging involved) - Reactivity with environment (moisture, light, oxygen, heat, compatibility). - Distribution - mechanical hazards of transport, including loading/unloading, impact (vibration, compression, piercing, puncturing), water or air transport. - Warehousing (climate or biological hazards). - Contamination/pilferage 76. How can you test Packaging integrity - checks for failure in an impervious stability in pack- container closure system (e.g. due to failure in seal integriaging? ty at the interface allowing ingress of moisture, oxygen, or microbial contamination). 12 / 13 77. What are the dif- bubble test (blister/strip pack, liquid bottles/cap), pressure ferent types of in- decay test (vial, ampoule, blister, pouches, IV bag), vacutegrity testing? um and dye test (vials, ampoules). 78. What are transport studies? Simulation tests provide damage-producing forces and conditions of transport environments such as vibration, drop height tests, temperature/humidity extreme, and dynamic/static compressive loads. 79. How is packag- Packaging is essential to the stability and shelf life. ing related to sta- Stability and shelf life relates to a particular packaging and bility of the drug? storage condition. 80. When should stability tests be carried out on packaging? - Stability testing studies should be conducted on the drug substance packaged in a container closure system that is the same as/simulates the packaging proposed for storage/distribution. - Stability testing should also be conducted on the dosage form packaged in the container closure system proposed for marketing, including any secondary packaging and container labelling. 13 / 13