packs and packaging · composition, dosage, name of manufacturer, characterization of storage...

Packs and packaging

Eduard Tichy, Bratislava, 2020

Faculty of Pharmacy, Comenius University

Packs and packagingPackaging is usually the final step in production of medicinal products. Proper selection and the type of packaging is crucial for their quality and performance. Within the lecture, followingtopics will be discussed:

• Classification of packaging – basic terminology

• Functions of packaging

• Types of packs

• Materials for packaging

All information is possible to find also in recommended textbooks, e. g. Pharmaceutics: The Science of Dosage Form Design 2nd Edition By Michael E. Aulton, Chapter 36, pp 554 – 570. It is available online at https://youngpharmacists.com/2014/04/10/pharmaceutics-the-science-of-dosage-form-design-2nd-edition-by-micheal-e-aulton/

https://youngpharmacists.com/2014/04/10/pharmaceutics-the-science-of-dosage-form-design-2nd-edition-by-micheal-e-aulton/

The basic classification of packs:

• Primary pack – the packaging, which is in direct contact with the medicinal product (e. g. blister for tablets, bottle for solutions or aerodispersions, etc.

• Secondary pack – packaging, which packs (envelopes) the primary packaging and protects it from outer environment (e. g. paper folding box for blister or bottle)

Packs and packaging - classification

There are 3 basic functions of packaging:

• Protection (will be discussed at the next slides)• Identification, information – packaging often carries

information about the product printed on its surface: its name, batch number, expiration date, composition, dosage, name of manufacturer, characterization of storage conditions, warnings and notes, etc.

• Convenience, compliance (pack is a part of dosage form, e. g. in case of aerosols the packaging includes a special component for aerosol creation (nozzle)

Packs and packaging - functions

Protective functions of packs include:

• Environmental protection

• Mechanical protection

• Protection from biological hazards


Environmetal protection includes protection from:

• Too high / too low temperature (BUT often a pack is not able to protect the product from extremes of temperature for a long time → it is important to ensure proper labelling of the product and to follow recommendations for storage conditions).

• Moisture and humidity (sensitive active substances and drug products might be decomposed by hydrolysis; medicinal powders can demonstrate caking (the loss of flowing properties); problem can be solved by a proper choise of material of the package impermeable for moisture and/or the use of desiccants).


Environmetal protection includes protection from:

• Light (sensitivity of the product may be solved by the use of a suitable packaging material impermeable for the light –metal, opaque plastics, paper for secondary packaging, etc.)

• Gases, volatile materials (O2, CO2, fragrances)

Some packaging materials (e. g. plastics) are quite considerably permeable for moisture and gases. Similarly as in the case of moisture protection, the problem can be solved by a proper choise of impermeable material of the package: glass, metals, laminates.


Mechanical protection includes protection from:

• Compression (during storage, packs stacked upon each other can be damaged by their own weight in case the packaging is not firm and resistant enough).

• Impact (dropping can happen accidentaly during handling with products; enough firm packaging can prevent the damage of product).

• Vibration (sufficiently massive and heavy packaging can e. g. minimize separation of powders caused by vibration during transportation; proper construction and design of closures, such as screw caps, may decrease the risk of their opening).


Protection from biological hazards includes protection from:

• Microbiological contamination (which is usually ensured by the integrity of the container and the use of proper closure).

• Insects, animals (the packaging should be resistant enough to withstand their attempts to get to the product itself).

• Humans (children or persons with the intention to compromise the integrity of packaging (e. g. unauthorized opening) are considered as human hazard; temper-resistant closures, child-resistant closures are the main tool to prevent this hazard – they will be discussed at next slides).


Types of packs will be discussed depending on dosage forms state of matter:

• Liquid dosage forms• Non-sterile

• Sterile

• Semi-solid dosage forms

• Solid dosage forms

Specialized types of packs / closures will be discussed within this part too:

• Child-resistant packaging

• Temper-resistant packaging

Packs and packaging - types

Types of packs for non-sterile liquid dosage forms (DF)

• Non-sterile DF may be represented by drops, syrups, solutions, nasal sprays, etc.

• Packagings typically used for these DFs are glass or plastic (PE, PP, PET) bottles with plastic closures, droppers, spray closures


Types of packs for sterile liquid dosage forms (DF)

• Sterile DF are usually parenterals and ophthalmic products packed to:

• Glass or plastic ampoules (A), glass or plastic vials closed with rubber closures (B), plastic packagings manufactured by Blow-Fill-Seal (BFS) technology – manufacture of the packaging and its filling is performed in one production step (C), prefilled syringes (next slide)


A B C

Luer ConeThe needle is slided on the PFS tip


Glass or plastic prefilled syringes (PFS) made from polypropylene (PP), Cyclo Olefin Polymer (COP) or Cyclo Olefin Copolymer (COC) are manufactured in various types depending on the construction of the tip and presence / absence of the needle.

Staked needleThe needle is a firm part of the syringe

Luer LockThe needle is fixed by a thread

Types of packs for semi-solid dosage forms

• Semisolids often used in medicinal practice are creams, emulsions, gels, ointments, pastes.

• They are usually packed to glass or plastic jars and tubes made from aluminium, plastics (PE) or laminates.


Types of packs for solid dosage forms

• Tablets and capsules are usually packed to bottles with wide bottle mouth made from glass or plastics with appropriate closures; another often used packaging type are blisters made from aluminium or plastics.

• Suppositories may be packed to plastic moulds.

• Other solid DF like powders and granules are packed to sachets, strips of sachets made from aluminium, plastics or layered paper.


Types of packs for solid dosage forms

• Powders for injections represent quite a special type of solid dosage form. They are prepared usually by a freeze-drying (lyophilization), which is performed in glass vials closed with rubber lyo-stoppers. After freeze-drying of the solution, vials are closed and serve as a final packaging.


Child-resistant packagings

• They are packs protecting the product from unintentional opening mainly by small children.

• The opening of the pack requires certain degree of strength and/or high degree of manual coordination to open the product (e. g. „push and rotate“).

• The drawback of this packaging type is sometimes even adults suffering from various disorders (arthritis) are unable to open them.


Temper-resistant packagings

• It is a packaging, whose construction can prove it was not opened before the first use by the customer (patient).

• Roll-On closure has a perforated collar and it must be broken before the cap can be unscrewed. Broken collar is the evidence the packaging was already opened.


Glass as a packaging material – its characterization

• Glass exhibits many advantages:

• It is a traditional material with many excellent properties.

• Glass is hygienic and suitable for sterilization by various sterilization methods; BE AWARE of possible colour change of glass during gamma-sterilization.

• Glass exhibit excellent barrier properties to moisture, vapours and gasses.

• It can be moulded into many shapes.

• Glass is relatively non-reactive, resistant to acids (except HF) and organic solvents, sensitive to alkalies.

Packs and packaging - materials

Glass as a packaging material – its characterization

• Glass exhibits also some disadvantages:

• Its density is quite high (higher costs during transportation may be expected)

• Glass is a fragile material, handlig with glass packaging should be with care.

• Gamma-sterilization can couse change of glass colour.


Reactivity of glass depends on its composition

• European Pharmacopoeia distinguishes three categories of glass: Typ I – III (Ph. Eur. 3.2.1)

• Type I glass : It is neutral glass, with a high hydrolytic resistance due to the chemical composition of the glass itself (boro-silicate glass). This type of glass is usually used for packaging of parenterals.

• Type II glass : It is usually soda-lime-silica glass with a high hydrolytic resistance resulting from a suitable treatment of the inner surface with acidic chemicals [e. g. (NH4)2SO4]; Type II glass is sometimes called „treated“ Type III glass.

• Type III glass : It is usually soda-lime-silica glass with only moderate hydrolytic resistance.


Plastics as a packaging material – their characterization

• Thermoplasts are almost the only group of plastics used in packaging; they soften and melt at higher temperature and can be moulded into many shapes. Most often used plastics are:


• Low and high density polyethylene (LDPE, HDPE), polypropylene (PP), poly(vinyl chloride) (PVC), poly(ethylene terephthalate) (PET) and poly(ethylene-vinyl acetate) (PEVA), polyolefins (copolymers of PE and PP)

• Cyclo Olefin Polymers and Copolymers (COP, COC)

COC

Plastics as a packaging material - their characterization


• PE, PP, PVC are the most often used thermoplasts; they have several characteristics, which should be taken into account during selection of proper packaging material:

• Advantage of plastics is that they can be formed to many pack types.

• Disadvantage is their relatively high permeability for vapours and gases (mainly PE); permeability for gasses significantly depends on their chemical composition: CO2:O2:N2 = 20:4:1 (permeation rate).

• Plastics contain a lot of aditives: fillers, colorants, plasticisers, softeners, catalysts and inhibitors of polymerization, antioxidants, etc., which might subsequently leache to drug product from packaging material.

Plastics as a packaging material - their characterization

• Many substances exhibit significant sorption to the plastics: preservative (with subsequent decrease of their concentration in the product and unsatisfactory protection from microbiological contamination), surfactants (followed by instability demonstration in dispersion systems), etc.

• Plastics are sensitive to various chemicals (organic solvents, surfactants, oils), which can damage their structure and deteriorate their properties.

• Some plasticsa, e. g. PVC or polystyrene (PS) exhibit poor impactresistance, they are relatively fragile.


Plastics as a packaging material – their characterization

• COP and COC have more advantageous properties in comparison with „traditional“ plastics:

• They exhibit much higher moisture barrier properties.

• They contain much less aditives, they represent high purity product with low extractables.

• Their optical properties are in many ways very similar to glass, they can be manufactured practically transparent.

• Their glass transition temperature (softening and melting point) is over 200°C; COP and COC are sterilizable by saturated steam (moist heat sterilization at 121°C)


Rubbers as a packaging material

• Rubber components (stoppers, plungers, tip caps for PFS) are often used as a part of glass or plastic packagings.


Two types of rubber are used in packaging:

• Natural rubber, which is prepared by vulcanization of natural latex.

• It is particularly suitable for multiple-use closures for injectable products, because it reseals after repeated insertion of a needle and does not produce fragments.

• Disadvantage is, it does not tolerate multiple autoclaving; additionally, it containes quite a lot of aditives, which may compromise the drug product quality.

• Synthetic (butyl-, bromobutyl- chlorobutyl-) silicone rubber

• It contains less aditives, exhibit lower sorption of other chemicals, it is less reactive than natural rubber.

• Synthetic rubber is less suitable for repeated insertion of needles, rubber stoppers tend to fragment.


Metals as a packaging material

• Aluminium and its alloys are almost the only metals used in packaging industry.

• Aluminium has a low density, it is strong material, totally impermeable for light, gases, chemicals. It is easy to work into variety of formats.

• Its disadvantage is reactivity, it dissolves in acids and alkalies. That is why its surface is usually treated with laquers and resins, which improve stability and resistance.


Laminates as a packaging material

• Laminates represent a complex packaging material. It is a combination of various materials, which create several layers of foils and films positioned one on another. Each layer has its own characteristic function. Laminates usually include:

• layer for decoration and information (PE, paper)

• layer for mechanical protection (PE, PP, PVC)

• layer for light and moisture barrier (Alu, EVOH – ethylene vinyl alcohol)

• layer for heat sealing (PE)

• Other combinations in laminates may be:

• paper / LDPE (e. g. packs for syringes or other single-use devices); PVC/PE; PE/Alu/PE (e. g. blisters for tablets)


Laminates as a packaging material

• Example of a laminate consisting from several layers of PE/EVOH/PE


Blisters from aluminium or plastics – example of the structure

• Plastics differ in permeability for moisture and gasses, therefore they are usually combined to achive desired properties.

*20°C/80% RH


Fibrous material as a packaging material

• Paper and cardboard is usually used as a secondary packaging material (folding boxes, labels); it may be used also as a part of a primary packaging material e.g. sterile sachets for syringes.

• Tyvek® is a fibrous material made of PE fibres. It is stronger and more resistant as paper, it does not release particles.


Regulatory considerations

• Materials and packaging types are discussed in several monographs of European Pharmacopoeia:

• Ph. Eur. 3.1.

Materials used for the manufacture of containers

• Ph. Eur. 3.2.

Containers (containers, syringes, closures)

Packs and packaging

• Ph. Eur. 3.1., Materials used for the manufacture of containers – list of monographs of particular materials

Packs and packaging

• Ph. Eur. 3.2., Containers (containers, syringes, closures) – list of monographs of particular packaging types

Packs and packaging

Packs and packaging

• Ph. Eur. 3.1., example of a monograph (silicon elastomers)

Packs and packaging

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packs and packaging · composition, dosage, name of manufacturer, characterization of storage...

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