Essential Pharma Documents: 2201:containers and closures

The qualities of good containers and closures/ideal properties of containers and closures

An ideal container must meet the following criteria.

It must preserve the physical properties of all dosage forms and protect them against damage or breakage.
It should protect the contents from the physical and mechanical hazards. These include vibration, compression, shock, puncture, abrasion etc.
It must protect the product against undesirable or adulterating chemical, biological or physical entities.
It should protect the contents from the atmospheric factors. For e.g. oxygen, Carbon dioxide.
It should protect the contents from the loss of product due to leakage, spillage or permeation.
It should not interact with the contents. This includes migration, absorption, adsorption or extraction.
It should protect the contents from the loss of water and volatile materials.
The container must not impart its own color, test or odor to the preparation.
It should be capable of withstanding extremes of temperature and pressure as well as to withstand handling while empty, while filling, closing, sterilizing, labeling, transport, storage and use by the customer.
It must not alter the identity of the product.
The container and closure must not react either with each other or with the preparation.
The closure must be easy to remove and replace.
The cost of the container and closure is an integral part of overall cost of the preparation, so it should not be high.
Apart from all these a container and closure should be attractive in appreance and must have sale promotion and marketing value.

TYPES OF CONTAINER

The containers can be classified into the following types.

Well closed containers: A well closed containers is used to protect the preparation from contamination by extraneous solids to prevent the loss of potency of active constituents and to prevent the loss of contents during transport, storage and handling.

Air-tight containers: Air-tight containers are used to protect the containers from atmospheric contamination of liquids, solids or vapors. They prevent the drugs due to efflorescence, deliquescence or evaporation.

Hermetically-Sealed containers: Hermetically sealed container is that which does not allow the air or other gases to pass through it. They are generally used for injectables.

Light-resistant containers: Light resistant containers are used to protect the drugs which undergo decomposition in the presence of light. For e.g .Amber colored glass or opaque glass.

Single dose containers: They are used to supply only one dose of the medicament. They are sealed in such a way that the contents cannot be removed without removing the seal, the contents so removed are consumed immediately..e,g. ampoules.

Multi dose containers: A multi dose container should hold a number of doses. It is sealed in such a way that success doses can be withdrawn easily without changing the strength, quality or purity of the remaining contents e.g multi dose vials.
Aerosol containers: Containers for aerosols must be strong enough to withstand the pressure evolved inside the container at the time of use of preparation.

Materials used for the making of containers

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Glass
Metals
Rubbers
Plastics
Fibrous material
Films, foils and laminates

Glass

Glass has been widely used as a drug packaging material. Glass is composed of sand, soda ash, limestone,& cullet. Si, Al, Na, K, Ca, Mg, Zn & Ba are generally used into preparation of glass

Advantages

They are hygienic and suitable for sterilization
They are relatively non reactive ( depending on the grade chosen)
They can be used on high speed packaging lines
They can be easily labeled.
They are transparent.
They are available in various shapes and sizes.
They can withstand the variation in temperature and pressure during sterilization.
They are economical and easily available.
They can protect the photosensitive medicaments from light during their storage.
They are neutral after proper treatment.
They are impermeable to atmospheric gases and moisture.
They have good protection power.
They do not deteriorate with age.
They can be sealed hermetically or by removable closures.

Disadvantages

It is relatively heavy
Glass is fragile so easily broken.
Release alkali to aqueous preparation.
They may crack when subjected to sudden changes of temperature.
Some containers can impart alkalinity and insoluble flakes to the formulations.

Flaking

During flaking the alkali is extracted from the surface of the glass containers and a silica rich layer is formed which sometimes gets detached from the surface and can be seen in the contents in the form of shining flakes.

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Fig; Flacking Fig:Weathering

Weathering

Weathering is a common problem with glass containers in which sometimes moisture condensed on the surface of glass container, can extract some weakly bonded alkali, leaving behind a white deposit of alkali carbonate.

Types of glass

Type I ( Neutral or Borosilicate Glass)

Type II ( Treated Soda-lime glass)

Type III ( Soda-lime glass)
NP—soda glass (non parenteral usage)

Colored glass
Neutral glass

PACKAGE TYPE	TYPE OF FORMULATION CAN BE PACKED	MINIMUM QUALITY OF GLASS THAT CAN BE USED
Ampoule	Aqueous Injectables Of Any pH	Type I
	Aqueous Injectables Of pH Less Than 7	Type II
	Non-Aqueous Injectables	Type III
Vial	Aqueous Injectables Of Any pH	Type I
	Aqueous Injectables Of pH Less Than 7	Type II
	Non-Aqueous Injectables	Type III
	Dry Powders For Parenteral Use (Need To Be Reconstituted Before Use)	Type IV
Bottles and Jars	Tablets, Capsules, Oral Solids & Other Solids For Reconstitution	Type IV
	Oral Liquids (Solutions, Suspensions, Emulsions)	Type IV
	Nasal & Ear Drops	Type IV
	Certain Types Of External Semisolids (Rubeficients, Local Irritants)	Type IV
	Blood & Related Products	Type I
Dropper	Auxiliary Packaging Device With Certain Kind Of Products	Type IV
Aerosol container	Aerosol product ( solution, suspension, emulsion or semisolid type)	Type I

METALS

Metals are used for construction of containers. The metals commonly used for this purpose are aluminium, tin plated steel, stainless steel, tin and lead

Advantages:

They are sturdy. (শক্ত)
They are impermeable to light, moisture and gases.
They can be made into rigid unbreakable containers by impact extrusion.
They are light in weight as compared to glass containers.
Labels can be printed directly on to their surface.

Disadvantages:

They are expensive.
They react with certain chemicals
They may shed metal particles into the pharmaceutical product.

COLLAPSIBLE TUBES METAL

The collapsible metal tube is an attractive container that permits controlled amounts to be dispensed easily, with good enclosure, and adequate protection of the product.
It is light in weight and unbreakable and lends itself to high speed automatic filling operations.
Most commonly used are tin, aluminium and lead.

Tin:

Tin containers are preferred for food, pharmaceuticals and any product for which purity is considered.
Tin is the most chemically inert of all collapsible metal tubes.

Aluminium:

Aluminium tubes offer significant savings in product shipping costs because of their light weight.
They are attractive in nature

Lead:

Lead has the lowest cost of all tube metals and is widely used for non food products such as adhesives, inks. Paints and lubricants.
Lead should never be used alone for anything taken internally because of the risk lead poison .
With internal linings, lead tubes are used for products such as chloride tooth paste.

PLASTIC

Plastics may be defined as any group of substances, of natural or synthetic origins, consisting chiefly of polymers of high molecular weight that can be moulded into a shape or form by heat and pressure.

Advantages

They are light in weight than glass and can be handled easily.
They are poor conductor of heat.
They have sufficient mechanical strength.
They can be transported easily.
Extremely resistant to breakage
They are available in various shapes and sizes.
They are resistant to inorganic chemicals.
They have good protection power.
Flexible
Variety of sizes and shapes
Essentially chemically inert, strong, rigid Safety use, high quality, various designs

Disadvantages

Absorption permeable to moisture
Poor printing, thermostatic charge
They are permeable to water vapour and atmosphere gases.
They cannot withstand heat without softening or distorting(বিকৃত করা,)
They may interact with certain chemical to cause softening or distortion.
They may absorb chemical substances, such as preservatives for solution.

Classes of plastics:

There are two classes of plastics, reflecting the behavior with respect to individual or repeated exposure to heating and cooling.

Thermoplastics

Capable of being shaped after initial heating and solidifying by cooling.
Resistant to breakage and cheap to produce and providing the right plastics are chosen will provide the necessary protection of the product in an attractive containers.
E.g. Polystyrene, polyethylene and polyvinyl chloride.

Thermosets

They need heat for processing into a permanent shape. During heating such materials form permanent crosslinks between the linear chains, resulting in solidification and loss of plastic flow.
E.g. Phenolic, urea and melamine are representative of thermosets.

Types of Plastics

Poly ethylene:

This is used as high and low density polyethylene

Low density polyethylene (LDPE) is preferred plastic for squeeze bottles.

High density poly ethylene (HDPE) is less permeable to gases and more resistant to oils, chemicals and solvents. It is widely used in bottles for solid dosage forms.

Polyvinylchloride (PVC): Used as rigid packaging material and main component of intravenous bags.

Poly Propylene: It has good resistance to cracking when flexed. Suitable for use in closures, tablet containers and intravenous bottles.

Polystyrene: It is also used for jars for ointments and creams with low water content.

FIBROUS MATERIALS

The fibrous materials are the important part of pharmaceutical packaging.
Fibrous materials include: Papers, Labels, Cartons, Bags, Outers, Trays For Shrink Wraps, Layer Boards On Pallets, etc.
The Applications as well as Advantages of Cartons include:

Increases display area
Provides better stacking for display of stock items
Assembles leaflets
Provides physical protection especially to items like metal collapsible tubes.
Fiberboard outers either as solid or corrugated board also find substantial application for bulk shipments.

Regenerated cellulose film, trade names Cellophane & Rayophane, is used for either individual cartons or to assemble a no. of cartons.

CLOSURES

Closures are the devices by means of which containers can be opened and closed. Proper closing of the container is necessary because

It prevents loss of material by spilling or volatilization.
It avoids contamination of the product from dirt, microorganisms or insects.
It prevents deterioration of the product from the effect of the environment such as moisture , oxygen or carbon dioxide.

Material used for closures

The closures for containers meant for storage of pharmaceutical products are generally made from the following basic materials.

Cork
Glass
Plastic
Metal
Rubber

Cork: Cork is essentially a wood obtained from the bark of oak tree. It is used for the manufacture of stoppers for narrow mouth bottles.

Fig:Cork

Glass: As compared to cork glass is an ideal material for stoppers but they do not provide leak proof closure as well as can easily slip out of the neck of the closure during transport and handling.

Plastic: As compared to cork, glass, rubber and metal Plastic closures are becoming popular day by day as they are unbreakable, light in weight and can be easily molded into various shapes and sizes.

Metal: Tin plate and aluminum are mostly commonly used for the manufacture of closures but aluminum is mostly used for this purpose.

RUBBERS (Elastomers):

Excellent material for forming seals, used to form closures such as bungs for vials or in similar applications such as gaskets in aerosol cans.

Categories of Rubbers:

Natural rubbers: Suitable for multiple use closures for injectable products as rubber reseals after multiple insertion of needle.

Synthetic rubber: Have fewer additives and thus fewer extractable and tends to experience less sorption of product ingredients.

Butyl rubber

Nitrile rubber

Chloroprene rubbers

Silicon rubbers

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Symbols Used On Packages And Labels

Many types of symbols for package labeling are nationally and internationally standardized. For product certifications, trademarks, proof of purchase, etc. identification code.

Unit Dose packaging

Blister Packing: In blister packing the unit dosage forms are enclosed in between transparent blisters and suitable backing material usually aluminum foil.

Strip Packing: In strip packing the unit dosage of drugs are hermitically sealed in between strips of aluminum foil and/or plastic film.

Advantages of Blister Package:

Prevention of broken glass bottles
Reduced costs and higher packaging speeds relative to other packaging materials.
Blister packaging helps retain product integrity because drugs that are prepackaged in blisters are shielded from adverse conditions.

Furthermore, opportunities for product contamination are minimal.
Each dose is identified by product name, lot number, and expiration date.
Blister packaging protects pharmaceuticals in the home better than bottles do.
Tamper evidence is another strength of blister packaging. The dosage units are individually sealed in constructions of plastic, foil, and/or paper. With blister packaging, however, each tablet or capsule is individually protected from tampering until use, so any form of tampering with a blister package is immediately visible.

Two basic types of pharmaceutical blister packages exist

In one variety the cavity is constructed of clear, thermoformed plastic, and the lid is formed of clear plastic or a combination of plastic, paper, and/or foil.
The other type of package contains foil as an essential component of both webs, and its cavity is created by cold stretching.

Cold Forming Blistering machine:

In the case of cold forming, an aluminum-based laminate film is simply pressed into a mold by means of a stamp. The aluminum will be elongated and maintain the formed shape.

Advantage of cold form foil blisters is that the use of aluminum is offering a near complete barrier for water and oxygen, allowing an extended product expiry date.

The disadvantages of cold form foil blisters are the slower speed of production compared to thermoforming and the lack of transparency of the package and the larger size of the blister card

Example: ALU-ALU Machine

Operation:

The sequence involves;

Installing the Aluminium Foil,
Cold forming it into blister cavities via punch pins,
Loading the blister with the product,
Placing lidding material over the blister,
And heat-sealing the package.
Cutting into individual blisters

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Thermo-cold forming blistering machine:

In the case of thermoforming, a plastic film or sheet is unwound from the reel and guided though a pre-heating station on the blister line. The temperature of the pre-heating plates (upper and lower plates) is such that the plastic will soften and become moldable.

Example: ALU-Tropical Machine

Operation:

The sequence involves;

Heating the plastic,
Thermoforming it into blister cavities,
Loading the blister with the product,
Placing lidding material over the blister,
And heat-sealing the package.
Installing the aluminium foil
Cold forming it into blister Pouch & seal it on thermoformed blister to give extra protection,
Cutting into individual blisters

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STRIP PACKAGE

It is commonly used for the packaging of tablets and capsules. A strip package is formed by feeding two webs of a heat sealable flexible film through a heated crimping roller.

The product is dropped into the pocket formed before forming the final set of seals. A continuous strip of packets is formed which is cut to the desired number of packets in length.