INTRODUCTION:

Packaging means a collection of different packaging materials which encase the pharmaceutical product from the time of manufacturing to the end of the user .encasing of drugs is important for life-saving drugs, medical devices, medical treatments, and new products like medical nutritionals. Poultice, liquid, solid, powder, suspension it should be transparent to the user about its whole information on the drug.^[1,2] different types of pharmaceutical packaging materials are present but it depends upon its function and type of the material used. Finally packaging materials are evaluated for sterilization, storage and certain stability studies. Packaging protects the harmful drugs from children direct contact because different types of packaging are produced in to market, they can’t easily open the packaging. ^[3] Packaging is an multiple user means provide presentation, protection, identification information, about a product during storage, carriage, display and until the product is consumed.^[4]

The quality of the packaging of pharmaceutical products plays a very important role in the quality of such products. It must^[5]

· protect against all adverse external influences that can alter the properties of the product, e.g. moisture, light, oxygen and temperature variations;

· protect against biological contamination;

· protect against physical damage;

· Carry the correct information and identification of the product.

A distinction must be made between primary and secondary packaging components. The primary packaging components (e.g. bottles, vials, closures, blisters) are in direct physical contact with the product, whereas the secondary components are not (e.g. aluminium caps, cardboard boxes). The choice of primary and/or secondary packaging materials will depend on the degree of protection required, compatibility with the contents, the filling method and cost, but also the presentation for over-the-counter (OTC) drugs and the convenience of the packaging for the user (e.g. size, weight, method of opening/reclosing (if appropriate), legibility of printing).Containers may be referred to as primary or secondary, depending on whether they are for immediate use after production of the finished product or not. Both single-dose and multi-dose containers exist. Containers may be well-closed, tightly closed, hermetically closed or light-resistant, airtight.^[^6]

Table 1:Types of raw materials used in packaging

Types of materials	Uses
Cardboard Boxes Display units	Boxes Display units
Paper	Labels, leaflets
Glass	Ampoules Bottles Vials Syringes Cartridges
Plastic	Closures Bottles Bags Tubes Laminates with paper or foil
Metals eg: aluminium	Collapsible tubes Rigid cans Foils Needles Gas cylinders Pressurized containers
Rubber	Closures, including plungers

Functions of packaging:

Containment:

The containment of the product is the most fundamental function of packaging for medicinal products. The design of high-quality packaging must take into account both the needs of the product and of the manufacturing and distribution system. This requires the packaging:

· Not to leak, nor allow diffusion and permeation of the product;

· To be strong enough to hold the contents when subjected to normal handling.

· Not to be altered by the ingredients of the formulation in its final dosage form.

· Protection

The packaging must protect the product against all adverse external influences that may affect its quality or potency, such as:

· light

· moisture

· oxygen

· biological contamination

· Mechanical damage.

Stability:

Information on stability is given in the guidelines for stability testing of pharmaceutical products containing well-established drug substances in conventional dosage forms.

For primary packaging, it is necessary to know the possible interactions between the container and the contents. Normally, product/component stability and compatibility are confirmed during the primary research and development stage. There are numerous possibilities of interactions between (primary) packaging materials and pharmaceutical products, such as:

· The release of chemicals from components of the packaging materials;

· The release of visible and/or sub visible particles;

· The absorption or adsorption of pharmaceutical components by the packaging materials;

· Chemical reactions between the pharmaceutical product and the packaging materials;

· The degradation of packaging components in contact with the pharmaceutical products;

· The influence of the manufacturing process (e.g. sterilization) on the container.

Labels:

Throughout manufacturing, a succession of specific outer labels is applied to the container of the medicinal product. The level of processing is indicated by the following words:

· Quarantine

· Storage

· Distribution.

Specifications for labels for finished drug products are defined in the WHO guidelines on GMP for pharmaceutical products .Written labels on the packaging:

· Permit the identification of each active ingredient by means of its INN, and also give the dosage form and the trade name/trademark. All information concerning the medicinal product, as required by national legislation, must be stated on the packaging.

· Preserve the stability of the medicinal product by giving advice on its storage

After the stability of the product has been evaluated, one of the following recommendations as to storage conditions can be prominently indicated on the label:

· Store under normal storage conditions;

· Store between 2 and 8 °C (under refrigeration, no freezing);

· Store below 8 °C (under refrigeration);

· Store between -5 and -20 °C (in a freezer);

· Store below -18 °C (in a deep freezer).

Permit the follow-up of a specific medicinal product by means of the batch number on the labels. It must be possible to follow the route of distribution of a product from the manufacturing process to its administration to the patient with the aim of locating and identifying products that are of potential risk (e.g. blood products, blood-derived products).

Mask the real identity of the medicinal product in clinical studies. This is extremely important in clinical trials in determining the real efficacy of a medicinal product in blinded studies. If the identity is masked by a code, it must be possible to disclose it at any time in a medical emergency.

Packaging material for different formulations ^[10]

solid dosage forms:

Tamper resistant packaging:

The requirement for tamper resistant packaging is now one of the major consideration in the development of packaging for pharmaceutical products. Tamper evident containers are closed containers fitted with a device that irreversibly indicates if the container has been opened.
The following package configuration have been identified by the FDA as examples of packaging systems that are capable of meeting the requirements of tamper resistant packaging as defined by FDA regulation

· Film wrappers

· Blister package

· Strip package

· Bubble pack

· Shrink seal and bands

· Foil paper or plastic pouches

· Bottle seals

· Tape seals

· Breakable caps

· Sealed tubes

Strip packages:

A strip package is a form of unit dose packaging that 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 either a heated crimping roller or a heated reciprocating plate. The product is dropped into the pocket formed prior to forming the final set of seals. A continuous strip of packets is formed, generally several packets wide depending on the packaging machine's limitations. The strip of packets is cut to the desired number of packets in length. The strips formed are usually collated and packaged into a folding carton. The product sealed between the two sheets of film usually has a seal around each tablet, with perforations usually separating adjacent packets. The seals can be in a simple rectangular or "picture-frame" format or can be contoured to the shape of the product .Different packaging materials are used for strip packaging based on their properties for high-barrier applications; a paper/polyethylene/foil/polyethylene lamination is commonly used.

Blister packages

When one thinks of unit dose in pharmaceutical packaging, the package that invariably comes to mind is the blister package. This packaging mode has been used extensively for pharmaceutical packaging for several good reasons. It is a packaging configuration capable of providing excellent environmental protection, coupled with an esthetically pleasing and efficacious appearance. It also provides user functionality in terms of convenience, child resistance, and no, tamperresistance.

The blister package is formed by heat-softening a sheet of thermoplastic resin and vacuum-drawing the softened sheet of plastic into a contoured mold. After cooling, the sheet is released from the mold and proceeds to the filling station of the packaging machine. The semi-rigid blister previously formed is filled with product and lidded with a heat-sealable backing material. The backing material, peelable type is usually heat-seal-coated aluminum foil. The coating on the foil must be compatible with the blister material to ensure satisfactory sealing, both for product protection and for tamper resistance. Materials commonly used for the thermo-formable blister are poly vinyl chloride (PVC), PVC/polyethylene combinations, polystyrene, and polypropylene. In tropical areas blister packages with an additional aluminium membrane is used which provide greater protection against high humidity

Child Resistant Containers commonly referred to as CRC's, are designed to prevent the child accessing the potentially hazardous product.

Bubble Pack:

The bubble pack can be made in several ways but is usually formed by sandwiching the product between a thermo formable, extensible, or heat-shrinkable plastic film and a rigid backing material. This is generally accomplished by heat-softening the plastic film and vacuum-drawing a pocket into the film in a manner similar to the formation of a blister in a blister package. The product is dropped into the pocket, which is then sealed to a rigid material such as heat-seal-coated paperboard. If a heat-shrinkable material is used, the package is passed through a heated tunnel, which shrinks the film into a bubble or skin over the product, firmly attaching it to the backing card.

Film wrapper:

A transparent film with a distinctive design is wrapped securely around a product or product container. The film must be cut or torn to open the container and remove the product. Substrates options include ultra destructible films, voidable films that provides image when removed. e.g., Solvent sensitive papers.

Shrink seals and bands

Bands or wrappers with a distinctive design are shrunk by heat or drying to seal the cap and container union. The seal must be cut or torn to remove the product. The shrink band concept makes use of the heat-shrinking characteristics of a stretch-oriented polymer, usually PVC. The heat-shrinkable polymer is manufactured as an extruded, oriented tube in a diameter slightly larger than the cap and neck ring of the bottle to be sealed.

Breakable caps

Such caps break when an attempt is made to open it. These caps provide external tamper evidence and can also be combined with the internal seals thereby providing double security

Sealed tubes

The mouth of the tube is sealed, and the seal must be punctured to obtain the product.

Shrink tubing

Foil, Paper, or Plastic Pouches

The flexible pouch is a packaging concept capable of providing not only a package that is tamper-resistant, but also, by the proper selection of material, a package with a high degree of environmental protection. A flexible pouch is usually formed during the product filling operation by either vertical or horizontal forming, filling, and sealing (f/f/s) equipment.:

Bottle Seals

A bottle may be made tamper-resister by bonding an inner seal to the rim of the bottle in such a way that access to the product can only be attained by irreparably destroying the seal. Various inner seal compositions may be used, but the structures most frequently encountered are glassine and foil laminations. Typically, glassine liners are two-ply laminations using two sheets of glassine paper bonded together with wax or adhesive. The inner seals are inserted into the bottle cap and held in place over the permanent cap liner by either by applying friction or by the a slight application of wax which temporarily adheres the seal to the permanent cap liner. If glue-mounted inner seals are to be used, glue is applied to the rim of the bottle prior to the capping operation.

Tape Seals:

Tape sealing involves the application of a glued or pressure-sensitive tape or label around or over the closure of the package, which must be destroyed to gain access to the packaged product. The paper used most often is a high-density lightweight paper with poor tear strength. Labels made of self-destructing paper are available; these cannot survive any attempt at removal once they have been applied. To reduce further the possibility of removing the label intact, perforation or partial slitting of the paper can be made prior to application so that the label tears readily along those weak points if any attempt is made to remove it.

Containers for semi solid and pressurized products^[11]

Semi solid dosage forms like ointments, creams, jell, emulsions, lotions, pastes, poultices.

1.Collapsible Metal and Plastic Tubes:

A Its narrow orifice prevents serious contamination of unused parts of contents.

B Wastage is reduced, since the patient is less likely to remove an excessive amount.

C When part of the preparation is expelled it is not replaced, as in other containers, by equivalent volume of air; consequently, microbial contamination and oxidative or hydrolytic degradation of the remaining contents are reduced.

D Nozzle type applicators can be fitted to facilitate administration into body cavities such as nose or vagina.

Most collapsible tubes are made of aluminum, although tin, lead, tin coated lead and plastics are also used. Aluminum tubes have good resistance to corrosion because the surface of film of oxide.

2.Glass Plastic Pots:

Suitable alternatives are wide mouthed squat, cylindrical pots made from glass or suitable plastics having a plastic (or occasionally metal) screw (or, sometimes in case of plastics, slip over cap). Glass pots may either be colorless and either clear or amber color or opal white. Glass is inert, hygienic and provides stability considerations allow transparency, the content can be seen. Unless returned by patient for reuse, they are more expensive than plastics.

Aerosols:
Pressurized packages expel the product through a valve. The pressure exerted for the expulsion of the product is an important consideration while selecting the packaging for any products.

Packaging of therapeutic active ingredients in a pressurized system. Aerosols are depends on the power of compressed or liquefied gas to expel the contents from containers. A dose can be removed without contamination of materials. Stability is enhanced for these substances adversely affected by oxygen and or moisture. When sterility is an important factor, it can be maintained while a dose is being dispensed.

Containers:

They must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge) at 1300 F. Containers are generally made up of glass or metal. But brittleness restricts the use of glass. If the pressure is less than 25psig and propellant content is less than 15% then glass can be used. Glass should be coated with plastic coating in two layers if pressure is less than or equal to 33psig. . Epoxy and vinyl resins can be used as linings. A vinyl coating on which the epoxy coating is most suitable for products having less PH.

Tinplated steel:

It is used for most aerosol as it is light inexpensive and durable. It is steel that has been plated on both sides with tin.

Tin plated steel containers are of two types: Two pieces container, three pieces container.

Aluminium:

Aluminium containers are more resistant to corrosion than tin-plated steel. Aluminium container is made by an extrusion process and hence has no seam. Aluminium is subjected to corrosion by water and alcohol.

Containers for liquids Parentrals

Injectable formulations are packaged in to containers made of plastic or glass. Container system includes ampoules, syringes, vials, bottles, cartridges, bags ampoules are all glass, and plastic are all bags. Rubber materials for rubber stoppers for vials and bottles, rubber plungers and rubber seals for syringes, cartridges. Irrigation solutions are packaged in glass bottles with aluminium screwcaps.^[12]

A single-dose container is one that holds a quantity of drug intended as a single dose and when opened cannot be resealed with assurance that sterility has been maintained. These containers include fusion-sealed ampoules and prefilled syringes and cartridges

Single dose containers

Hold the product that is intended for single use. An example of such a container is the glass ampoule.

Multi dose containers

A multiple-dose container is a hermetic container that permits withdrawal of successive portions of the contents without changing the strength or endangering the quality or purity of the remaining portion (vials). The device is usually a spoon or a cup of volume 5ml.

Hold a quantity of the material that will be used as two or more doses. An example of this system is the multiple doses vial or the plastic tablet bottle.

Well closed containers

Protect the product from contamination with unwanted foreign materialsAnd form the loss of contents during the use.

Air tight containers

are impermeable to solids, liquids and gases during normal storage and use. If the container is to be opened on more than one occasion it must remain airtight after reclosure.

Light resistant containers

Many pharmaceutical products require light-resistant containers. In most instances, a container made of a good quality of amber glass or a light-resistant opaque plastic will reduce light transmission sufficiently to protect a light-sensitive pharmaceutical. Agents termed ultraviolet (UV) absorbers may be added to plastic to decrease the transmission of short UV rays. A recent innovation in plastic packaging is the coextruded two-layer, high-density polyethylene bottle, which has an inner layer of black polyethylene coextruded with an outer layer of white polyethylene. The container provides light resistance (exceeding amber glass) and moisture protection. It is increasingly being used in the packaging of tablets and capsules^.[^12,13]

protect the contents from the effect of radiation at a wavelength between 290nm and 150nm.

Closures^[^14,15]
The closure is normally the most vulnerable and critical component of a container in so far as stability and compatibility with the product are concerned. An effective closure must prevent the contents from escaping and allow no substance to enter the container.

Function of a closure:

· Provide a totally hermetic seal.

· Provide an effective seal which is acceptable to the products.

· Provide an effective microbiological seal.

Types of closures

Closures are available in five basic designs

· threaded screw cap

· Lug cap

· Crimp-on (crowns)

· pilfer proof closure

· Roll-on

Many variations of these basic types exist, including vacuum, tamperproof, safety, child resistant, and liner less types, and dispenser applicators.

Threaded Screw Cap:

The screw cap when applied overcome the sealing surface irregularities and provides physical and chemical protection to content being sealed. The screw cap is commonly made of metal or plastics. The metal is usually tinplate or aluminum, and in plastics, both thermoplastic and thermosetting materials are used.

Lug Cap:

The lug cap is similar to the threaded screw cap and operates on the same principle. It is simply an interrupted thread on the glass finish, instead of a continuous thread. It is used to engage a lug on the cap sidewall and draw the cap down to the sealing surface of the container. Unlike the threaded closure, it requires only a quarter turn.The lug cap is used for both normal atmospheric-pressure and vacuum-pressure closing.

Crown Caps:

This style of cap is commonly used as a crimped closure for beverage bottles and has remained essentially unchanged for more than 50 years.

Roll-On Closures:

The aluminum roll-on cap can be sealed securely, opened easily, and resealed effectively. It finds wide application in the packaging of food, beverages, chemicals, and pharmaceuticals. The roll-on closure requires a material that is easy to form, such as aluminum or other light-gauge metal. Re sealable, non re sealable, and pilfer proof types of the roll-on closure are available for use on glass or plastic bottles and jars.

Pilfer proof Closures:

The pilfer proof closure is similar to the standard roll-on closure except that it has a greater skirt length. This additional length extends below the threaded portion to form a bank, which is fastened to the basic cap by a series of narrow metal "bridges." When the pilfer proof closure is removed, the bridges break, and the bank remains in place on the neck of the container. The closure can be re sealed easily and the detached band indicates that the package has been opened. The torque is necessary to remove the cap.

Suppositories package^[^16]

Bottle packing

Plastic bottles and these are sealed by aluminium taggers. Such bottles are further packed in an e-flute carton which contains bottles. Such e-flute cartons are then finally packed in to a master corrugated shipper.

Strip packing

Pouch type strip packing, these strips are of 4 ply material [poly+aluminium+poly+paper (inner layer poly and extreme outer layer-paper)]

strip pack is superior to blister pack in the 3 ways

· The product i.e. suppository can be removed easily without breakage which happens many times with blister pack.

· Often blister pack requires refrigeration to avoid deformity in shape this is not the case in strip pack

· Strip pack is of 4 ply material including aluminium which has better moisture barrier properties and hence the product is more stable as compared to blister pack which is usually of pvc.

UPVC FILM- (UNPLASTICISED POLYVINYL CHLORIDE)

Glossy white film for suppository packaging.PVC/PE/PVDC. Packaged in a tamper resistant

packaging.

Packaging for liposomes^[17]

Hermetically sealed borosilicate glass ampoules

Provide a secure environment for lipids sensitive to oxidation. The ampules are shipped in cardboard liners for protection and storage convenience. Ampules are pre-scored for easier opening. Once the seal is broken, sample may be transferred to a Screw Cap Storage Vial (see below).

Narrow-mouth borosilicate glass bottles
Convenient for shipping and storage of larger volumes of lipids. The closure system is composed of a closed-top screw cap with a teflon liner fused to a silicone rubber backing. The liner is sonically welded to the cap, therefore no glue can come in contact with the organic solution.

Wide-mouth borosilicate glass bottles
Convenient for shipping and storage of dry powder lipids. Larger openings provide easier access to lipid samples. The closure system is composed of a closed-top screw cap with a teflon liner.

The Screw Cap Storage Vial
Designed as a storage option for materials shipped in glass ampules or bottles. The closure system contains an open-top screw cap with a teflon liner fused to a silicone rubber septum.

Transdermal patches packaging

Backing Film:

Occlusive films of varied composition and/or thickness.

Adhesive:

An adhesive layer that incorporates the active ingredient; featuring silicone, acrylic and/orpolyisobutylene adhesive formulations.

Release Liner:

Removable coated film or polymer based protective layer.

CONCLUSION:

Packaging plays its most visible and catalytic role in a modern economy with the widespread adoption of branding of products and development of consumer preferences. to the extent that any consumer product is packaging in a manner that meets the criteria of safety, convenience and attractiveness. There is a lot of going in new packaging technologies. This article has reviewed only a fraction of each area of packaging material in pharmaceutical packaging.

AKNOWLEDGEMENTS:

All the authors are thankful to Chalapathi Institute of Pharmaceutical Sciences for providing necessary facilities to bring out this work.

REFERENCES:

1 Jain UK, Nayak S. 1st ed. Hyderabad: Pharma Med Press; 2008. Pharmaceutical Packaging Technology; pp. 1–273.

2 Carter SJ. Copper and Gunn's Packaging in Tutorial Pharmacy. 2005:133–41.

3 M.E. Aulton. “The Science of Dosage Form Design”, Secondedition.pageno:554-570

4 World Health Organization, 2002. Guidelines on packaging for pharmaceutical Product, Annex 9, 2002.tests on biodegradable plastic materials. (WHO Technical Report Series, No. 902).

5 (WHO Technical Report Series, No. 902) http://www.who.int/ medicines/areas /quality assurance/regulatory standards/en/index html

6 World Health Organization. Annex 9, Guidelines on packaging for pharmaceutical products, WHO Technical Report Series, No. 902, 2002.

7 Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva, World Health Organization, 1992, Annex 1 (WHO Technical Report Series, No. 823).

8 Trends in pharmaceutical packaging. [Last accessed on 2001 Oct 19]. Available from:http://www.ngpharma.eu.com/article/Trends-in-pharmaceutical-packaging

9 Matthew S. Thomas Associate Senior Consultant Engineer, Pharmaceutical Packaging Development, Eli Lilly and Company October 2nd, 2010

10 Manoi, Shekhawati College of pharmacy, Dundlod. Pharmatutor. Review on: the pharmaceutical packaging

11 Availableonline http://www.ipharmsciencia.com.Internationale Pharmaceutica Sciencia 2012; 2:2.

12 Michael J. Akers, PhD. http://www.pharmpress.com/ files/docs/Remington_Ch_26.pdf, Sample chapter from Remington: Essentials of Pharmaceutics, Parenteral Preparations pg no 495-532

13 Packaging/Container Issues: Unit-dose, Pre-filled Syringes, Pre-packs, Etc. International journal of pharmaceutical compounding.2011;1: 6

14 Mehta Kunal C, Akhilesh.D and Shyam Kumar.B, Recent Trends in Pharmaceutical Packaging: A review. International journal of pharmaceutical and chemical sciences .2012; 1:3. pg no: 932-944

15 Devi KV, Burande M, Deepak H, Jobanputra SB. Packaging solutions to the changing pharma market needs. Pharma Times. 2007; 39:29–34.

16 .http://www.meridianentp.com/product-sub/meridian_newsuppository.php.suppository packaging

17 http://avantilipids.com/index.php?view=itemsandcid= 5andid=13andoption=com_quickfaqandItemid=385.Packaging for liposome’s

Received on 02.07.2014 Accepted on 05.08.2014

Asian J. Res. Pharm. Sci. 4(3): July-Sept. 2014; Page 140-150

Degree of Concern Likelihood of Packaging Component-Dosage Form Interaction Associated with the Route of Administration	Likelihood of Packaging Component-Dosage Form Interaction
	High	Medium	Low
Highest	Inhalation Aerosols and Solutions; Injection and Injectable Suspension	Sterile Powders and Powders for Injection; Inhalation Powders
High	Ophthalmic Solutions and Suspension; Transdermal Ointments and Patches; Nasal Aerosol and Sprays
Low	Topical Solutions and Suspensions; Topical and Lingual Aerosols; Oral Solutions and Suspension	Topical Powders; Oral Powder	Oral Tablets and Oral (Hard and Soft Gelatin) Capsules

Packaging for liposomes[17]

Packaging for liposomes^[17]