Containers and closures for dispensed products

Md. Imran Nur ManikLecturer

Department of PharmacyPrimeasia University

IntroductionPackaging is the process by which the

pharmaceuticals are suitably packed so that they should retain their therapeutic effectiveness from the time of their packaging till they are consumed.

It is the art and science which involves preparing the articles for transport, storage, display and use.

ContainerA container may be defined as a device in which

the drug is enclosed and is in direct contact with the drug.

Closures A closure is a device which seals the container to

exclude oxygen, carbindioxide, moisture, micro-organisms and prevent the loss of volatile substances.

It also prevents the loss of medicament during transport and handling.

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.

TYPES OF PACKAGINGPrimary packaging is the material that first envelops the product and holds it. This usually is the smallest unit of distribution or use and is the package which is in direct contact with the contents. Examples: Ampoules,Vials ,Containers ,Dosing dropper ,Closures (plastic, metal) ,Syringe ,Strip package, Blister packaging.

Secondary packaging -Is outside the primary packaging perhaps used to group primary package together. Ex. Boxes, cartons

Tertiary packaging is used for bulk handling , warehouse storage and transport shipping. The most common form is a palletized unit load that packs tightly into containers.

Apart from primary and secondary packaging, two types of specialpackaging are currently in use, as follows:

• Unit-dose packaging. This packaging guarantees safer medication by reducing medication errors; it is also more practical for the patient. It may be very useful in improving compliance with treatment and may also be useful for less stable products.

• “Device” packaging. Packaging with the aid of an administrationdevice is user-friendly and also improves compliance. This typeof packaging permits easier administration by means of devicessuch as prefilled syringes, droppers, transdermal delivery systems,pumps and aerosol sprays. Such devices ensure that the medicinalproduct is administered correctly and in the right amount 

TYPES OF PACKAGING MATERIAL

I) Glass

II) Metals

III) Rubbers

IV) Plastics

V) Fibrous material

VI) 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.

WeatheringWeathering 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

PACKAGE TYPE TYPE OF

FORMULATION CAN BE PACKED

MINIMUM QUALITY OF

GLASS THAT CAN BE USED

Bottles and

Jars

Tablets, Capsules, Oral Solids & Other Solids For

ReconstitutionType 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 impermeable to light, moisture and gases.• They are sturdy. • They are made into rigid unbreakable containers by impact

extrusion. • They are light in weight compared to glass containers.• Labels can be printed directly on to their surface.Disadvantages:• They are expensive.• They react with certain chemicals

COLLAPSIBLE TUBES METAL • The collapsible metal tube is an attractive container that

permits controlled amounts to be dispensed easily, with good reclosure, 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 natureLead: • 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( বি�কৃত করা,) • They may interact with certain chemical to cause softening or distortion.

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 PLASTICSPOLY ETHYLENE: This is used as high and low density polyethyleneLow 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.

CLOSURESClosures 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 are; 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.

• 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 rubberNitrile rubberChloroprene rubbersSilicon rubbers

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 .

Fragile This way up Keep away from sunlight Keep away from water

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 packaging1. Prevention of broken glass bottles2. Reduced costs and higher packaging speeds relative to other

packaging materials.3. Blister packaging helps retain product integrity because drugs

that are prepackaged in blisters are shielded from adverse conditions.

4. Furthermore, opportunities for product contamination are minimal.

5. Each dose is identified by product name, lot number, and expiration date.

6. Blister packaging protects pharmaceuticals in the home better than bottles do.

7. 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

1. 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.

2. The other type of package contains foil as an essential component of both webs, and its cavity is created by cold stretching.

Blister Packaging machineCold 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 MachineOperation:The sequence involves;1. Installing the Aluminium Foil, 2. Cold forming it into blister cavities via punch pins, 3. Loading the blister with the product, 4. Placing lidding material over the blister, 5. And heat-sealing the package. 6. Cutting into individual blisters

1. Bottom foil uncoiler 6. Cover foil uncoiler 11. Discharge conveyor 2. Cold forming station 7. Cooling & slitting 3. Feeding device 8. Draw Off 4. Empty checker 9. Punching 5. Sealing & Embossing 10. Waste foil coiler

Blister Packaging machineThermo-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 lineThe temperature of the pre-heating plates (upper and lower plates) is such

that the plastic will soften and become moldable. Example: ALU-Tropical MachineOperation:The sequence involves;1. Heating the plastic, 2. Thermoforming it into blister cavities, 3. Loading the blister with the product, 4. Placing lidding material over the blister, 5. And heat-sealing the package. 6. Installing the aluminium foil7. Cold forming it into blister Pouch & seal it on thermoformed blister to give

extra protection, 8. Cutting into individual blisters

STRIP PACKING• 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.

• The materials used for strip package are cellophane, polyester, polyethylene, polypropylene, polyvinylchloride.

REFERENCES :-– Dean DA, Evans ER, Hall H. Pharmaceutical packaging

technology ,1st ed,Pg:210-65.– Remington.The Science and Practice of Pharmacy,

21st ed,Vol-1;Pg:1047-10 .– Indian Pharmacopiea,2007,Vol-1;Pg:599-25 – Leon Lachman, Liberman AH, Kanig JL.The Theory

and Practice of Industrial pharmacy,4thed,Pg:711-22. – Hanlon J. Handbook of Packaging

Engineering.4thed;Pg:412-49

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References:-

• Pharmaceutics-1 by R.M.Mehta, Page No.:-74-85• The Theory and Practice of Industrial Pharmacy

by Leon Lachman, Page No.:-711-724• Pharmaceutical Product Development by

N.K.Jain, Page No.:-341-377• Aulton’s Pharmaceutics by Michael E. Aulton,

Page No.:-626-638

Design validation results shall include: the design identification, name of the individual(s) performing the validation, method(s) used, and the date. All of this information should be recorded in the design history file. If any significant change is made in the packaging or packaging operation after validation, the new process will need to be revalidated.

One of the most difficult aspects of package validation is determining how many samples to test. The goal is not to over test because of cost considerations while still running sufficient tests to provide statistically valid sampling. Statistical methods of analysis are important in process validation. The following decision tree from Medical Device and Diagnostic Industry, "Streamlining Package-Seal Validation," October 1992, provides various methods of statistical analysis. The manufacturer is challenged with determining which statistical method is most applicable to their individual needs. The resulting validation plan should identify, measure, and evaluate the key processes and variables that will require assessment to complete a validation or revalidation of the packaging and the packaging process.