Introduction

Packaging

Packaging is a term defined as a product protecting element during the course of distribution, storage, transportation, sale, and until it reach s the enduser. It involves the processes of evaluating, designing and manufacturing the product. Packaging design plays an important role from the process of transportation, logistics, sale [u1]. The designing of a package plays a vital role. Without packaging nothing can be done. It is an inclusive business across the globe, The major aspect of the drug industry is to maintain the quality, standards of the pharmaceutical product from the initial stage to the final consumer acceptance. The product acceptance depends on the integrity and stability of the consumers, which can be achieved by meeting the criterion of appropriate packaging There are various dosage forms, like, the tablets and capsules in solid forms, syrups and emulsions in liquid forms creams, pastes, gels and biological products in semi solids, blood and blood products, crude drugs etc. All these products require to be packed without any alteration in their therapeutic aspects. The packaging of the pharmaceutical commodities is a quintessential factor. It has a direct impact on end-user. If the package is good, it lasts long and if it is poor, it goes out of the market. To increase the marketing and distribution of the pharmaceuticals globally, customization of the packaging such as designing, dimension of the boxes, logos etc. should be taken care of. The environmental aspects relating to the sustainability is also crucial. The pharmaceutical packaging departments play a role in the technological advancements of packaging and their modifications have lead to face the challenges in packaging that are evolving from time to time (Pareek & Khunteta, 2014).

Different categories of packaging

Primary packaging

In this packaging the packing material is directly in contact with the product or instrument. It should not interact with drug and free from contamination of the dosage form. E.g. Blister packaging.

Secondary packaging

This packaging is a successive covering material and it’s not only protecting the material but also protects the primary packaging product. E.g. cardboard box and cartons etc.

Tertiary packaging

It is one of the third types of wrapping used to protect manufactured pharmaceutical goods. And it provides large volumes of shipping and handling of material from one spot to another. E.g. container, brown cardboard boxes, wooden pallets and shrink wrap (Mallik, 2018).

There are two type of primary packaging

• Glass

• Plastic

Glass

Glass containers should be chemically inert, impermeable with the dosage form and it should approve by FDA clearance.

The following are the types of glass materials used in pharmaceutical packaging in manufacturing industry

• Borosilicate glass

• Treated soda-lime glass

• Regular soda lime glass

• General purpose soda lime glass

Plastic containers

These containers are of high quality and it can be designed in different forms. These packagings have highl resistance to damage.

The Plastic containers are standardized and classified. They are as follows

• Polyethylene (PE)

• High- density polyethylene (HDPE)

• Polypropylene (PP)

• Low density polyethylene(LDPE)

• Polyvinyl chloride (PVC)

• Polystyrene(PS)

• Nylon (polyamide)

• Polycarbonate

• Polyactic fibers

• Acrylic multipolymers (Nitrile polymers)

• Polyethylene terephthalate (PET or PETE) (Approach, 2019).

Materials are used in pharmaceutical packaging

Initially, majority of the medicines, almost fifty one percent (51%) were consumed from the blister packs in the form of tablets and capsules. Or, it was packed in pharmaceutical plastic bottles. This was the state of affairs, especially in the USA. Oral liquid medicines were also administered thus. The medicines administered had their course of movement. The packaging depended on the form of medicine and their dosage quantity. Most of the packaging included parenteral (30%) inhalation drugs (19%), and transdermal (5%) methods. These types of packaging create an impact on the pharmaceutical industry and gives 100% effectiveness of the dosage form (Kunal, 2012).

Current trends and technology of pharmaceutical packaging

Tamper evident packaging systems

Tamper- evident packaging – the end-user gets to know clearly if the product is tampered. Materials like tin is hermetically sealed and multilayer aseptically packed cartons are used. Some of the tamper-evidence packaging systems are as follows

Film packaging

It is a clear film sheet or wrappers with a specific design which packed firmly around the material. Then the film wrapper is removed by cutting or tearing to open the product. There are several substrate options for film wrappers that provides image when removed, these include ultra-destructible films, voidable films, etc.

Shrink seals and bands

In shrink seal techniques the wrappers or bands are in specific design and shrinking takes place by heating techniques or drying the cap sealing. And the seal is removed by tearing or by cutting.

Breakable caps

In breakable caps the caps are opened or break when the product is to be used. It provides highly external tampered evidence and also provides double safety by sealing internally too.

Sealed tubes

Tube opening is to be sealed and the sealed mouth tube has to be pierced or to be broken to use the product.

Hidden attributes

Forged outcomes can be observed by owners with the help of hidden features which won’t be noticed by the common crowd. The hidden attributes should be installed in such a way that it can’t be modified easily without expert intervention. It is important that these features should remain anonymous, else, the safety and security will be compromised.

Packaging designs: Substrates/Materials and other design options

Substrates

For the packaging design there will be varieties of substrates for the purpose of tamper evident and in counterfeit attributes like acetate, polystyrenes, destructive vinyl’s etc. UV fluorescing fibers or chemical materials in the paper are incorporated as hidden markers in the substrate.

Packaging designs

The packaging designs like aerosol and sealed containers are secure enough from counterfeiting.

Sealing systems

In packaging, foil seal is preferred, for, it is tamper proof. Thus it is used in aluminum blister packs, tray packaging, flexible packaging, etc.,

Security labels

Security labels give information and knowledge about the product to the consumer, thus helps the same to identify the fake product. Substrate generates an admiring communication of the pressure susceptible adhesive in the self-adhesive labeling. Now-a-day’s passive security labels are widely used in pharmaceutical industries. Some of the security labeling as follows,

Paper labels with security cuts

Uncoated paper or standard coated papers are used as substrate. The label printer designs the paper labels securely at the sterilization stage. Using a special cutting die, the face material is cut in different angles. This ensures that the packing is not fiddled with. If anyone tries to tamper with the product label, it tears along with the paper on which it is glued.

Abolishable labels

New superior substrate is needed to design an aim. Cellulose ester film is used as a substrate to most of the flagship products. The film is extremely in an elaborate way designed to have an adequate power to endure change into label bonds in roll type. It’s made in universal forms and eventually created into high pressure sensitive labeling. The labels are typically automatically dispersed on reflex label dispensers and once scraped off, it breaks‑up into really little fragmented things. The economical vinyl changes into acetate film. A mixture of various artificial polymers are typically accustomed inform little inherent asset to the substrate.

Self destructing paper label

The labels square measure terribly like abolishable tags as point out earlier. In this case, terribly weak substrate is used, terribly weak strength paper of low grammage. And the fillers square measure loaded on the paper that making a weak and brittle paper. Because of the dearth of strength and firmness within the substrates it's terribly troublesome to get rid of and fragments simply. The papers square measure terribly difficult to supply since the paper mills are try to improve papers with a great strength.

Multi superimposed labeling

Laminated face stock label of various substrates are dependent on the need of the protection labeling, which can be a dissimilar coatings. And this layers are intended such on parting and they show tamper proof, by manufacturing a 1 layer obtaining fiber tear, in different cases by complete parting and displaying a pattern. By adhesives and warmth application the layers are secure that depend on the need of the look of the label.

Transfer labels

These substrate materials contain neither polyester nor BOPP. The matter is written on the peel off coat or the discharge coat of the film. Additionally, an adhesive is coated. Such labels once useful and stark naked off, the high layer comes off dead the written substance behind. This can be additionally created by printing of subsurface and some written substance is on and peeled off by the outer upper layer.

Coding, graphics and printings

Cryptography and marking

For an extended time, restrictive compliance drove and also the marking and cryptography on the pre packed merchandise beginning with before the date. But, it associate with increasing alertness a better printing and pattern choices similar to ink jet cryptography, optical maser cryptography associated electrolytic etching for metal marking on are often accustomed offer an overall anti‑counterfeit impact. These have the capability to try to on-line cryptography with flexibility, offer several programmable options, saves time and square measure of low prices. On the utilization of those, one will select the bit dry contactable cryptography, non-contactable cryptography or the permanent optical maser cryptography etc.

Security graphics

A skinny line colored prints that can be comparable to note printing that requires a big selection of overt and covert style parts like as guilloches and line boss. They’ll be used as background separate zone like an overprint space, or for complete packing graphics, and may be written by normal offset lithography. The utilization of pastel “spot” colors makes the look finds difficult to scan and repeat the process and security are frequently enhanced by a spread of covert style parts, like micro text and latent pictures.

Holograms

This is used for initial publicity functions during 80’s and displayed an outstanding growth by 1996. The leading accustomed public feature is that the “dove” holograph that is employed to protection of credit cards for several years. A holograph commonly includes a picture with some of the 3‑D construction, special parting. Holograms associated optically variable devices (OVD) are often created more practical once combined in an essential a part of the first pack (example like blister foil) or with a tamper evident feature. They’ll be combined into slit bands in over wrapper films fixed in paper substrates; therefore it's helpful for secondary transport packs. Many processes are often inured embody in holograms into wrapping like portable cartons and versatile. These methods embody high pressure delicate, shrink, hot imprinting and net transmission. Fundamentally selection choices for the holograph square measure the media and copy. The true combination of the 2 elements create an anti‑counterfeiting pattern that encounters the desired objective.

Optically variable devices

Optically variable devices (OVDs) additionally concerned a very extensive range of replacement devices and it's like holograms, however often without any 3D element. Generally, associate images involve in transitions or flips and additionally with monochromatic contrasts or color transformation. Like holograms, it is made‑up of a transparent film that's the image carrier, and a really skinny coating of metal could also be a reflective backing layer is used. Additional security are often done by the method called incomplete de‑metallization, where by a number of the contemplative layer is chemically detached to administer associate involved define to the image, as are often seen on several banknotes. Within the different means, a transparent film of the contemplative image is often seen because of the reflective layer, with additional of a ghost contemplative image noticeable under at such viewpoints of observing and illumination.

Invisible printing

For printing any substrates, special inks and invisible markings square measure used and that solely seem below certain conditions, like via actinic radiation. They’ll be formulated to point out totally dissimilar colors with illumination at dissimilar wave lengths.

Entrenched image

An unseen image is often mounted inside the pack graphics which are often viewed employing an extraordinary filter, and can't be repeated by outdated scanning conditions. The properties of image are often quite dramatic.

Digital watermarks

Invisible information are often digitally determined inside the graphics features and tested by means that of a personal to blame and exceptional software. The info is often recorded by exploitation digital camera, mobile phone or exploitation scanning instrumentality, however, the digital evidence isn't visible to the human eye, and makes an attempt to development are identified by asset of the degradation of the entrenched information.

Covert marks and printing

Specific symbols and design is also obtained in numerous ways that leads to lack of attention and is tough to repeat.

Forensic markers

There square measure several laboratory testing’s proving legitimacy of product.

Chemical taggants

Specific chemical agent is employed to search out the Trace chemicals and might be detected, however not commonly identified by standard analysis.

Biological taggants

It is often used at very low-level (PPM or lower) in manufactured goods coating or formulation untraceably applied to packed elements. They realize tough to predict their concentrations at low levels they're undetectable by traditional analytical ways, therefore need extremely exact “lock and key” chemical agent kits to demonstrate.

Polymer taggants

Extremely exact DNA targeting “lock and key” chemical agent methods will be involved to wrapping by a range of printing ways. It requires a “mirror image” recombinant strand to have a consequence on the pairing, and this chemical molecular reaction is measurable by a fervent instrument. Protected by activity the marker and reagent pair in an exceedingly medium of random polymer strands, however the check works solely with one recombinant combine.

Atom ratios

Naturally obtained isotopes square measure extremely distinctive of the basis compound, and exactly determined by optical device light. They’ll offer a “fingerprint “of one or many of the merchandise components, or as an alternative marker additional with its specific distinctive sign. High-quality laboratory instrument is needed for detection.

Mass encoding/trace and track technologies

The process of the stock solely bound identification codes are assigned, that is employed until the ultimate product consumption. The cryptography holds an information that is secure and handled by those who are involved. The secured encoded information is read by using radio instruments. Chaste of the label is significantly increased by the presence of distinctive and apparently random publishing, ideally at individual item level. If it's in a serial manner it's straightforward to search out, however once it's irregular it's tough and uses secure algorithmic rule. Duplication of the info is known. Individual merchandise square measure encoded in associate degree overt manner either through a barcode or somebody's decipherable kind. Secret writing so becomes the vital in style method, for, Encoded merchandise wants the utilization of software package solutions that permits the manufactured goods tracing through the varied nodes within the supply and provides chain management (LSCM) operations. Choices approved for cryptography are

Barcodes

Barcode could be a sequence of similar, areas and head-to-head bars used to encrypt the tiny thread of information. 2‑D codes are accessible now with risk to encrypt giant volume of knowledge that made it associate degree possibility for anti‑forging. Bar‑coding once used with GS‑1 normal, allow widespread and distinctive recognition of product, properties etc., A code scanner interprets the code exploitation intensity of the sunshine mirrored. While packing, printing offers product attractiveness and receipt by the buyer, Barcodes capture detailed data which contain detection and traceability of data, safety, identification, etc. Barcodes offer the means that for automatic data assortment. It documents universal and distinctive identification and privacy of pre-packed merchandise once it's used world list norms. Barcoding mechanism is primarily with the optically scanning devices e.g., for the Universal Product Code (UPC) barcode analyzer are used an element inert gas (red) optical device emitting 660 nanometers to work out the distinction between dark bar mirrored light-weight and lightweight areas. for his or her use as a system they conjointly would like the decoders, software’s for secret writing. Universally,GS-1 barcodes offer associate degree access that might operate with countries/users. United Nations agency square measure the members of GS-1. But, due to some particular reason several merchandise chains use their branded codes. Barcodes are used as anti-counterfeit possibility, which is tried, particularly, with the chances to travel for 2-D code

Digital mass coding

It is just like the digital mass publishing except for the manner code is created. During this method encoded codes square measure created by a scientific discipline algorithmic rule. The codes itself don't carry or have any product or provision data. There’s no would like for maintaining an information base (Zadbuke, Shahi, Gulecha, Padalkar, & Thube, 2013).

Blow-fill-seal technology

This is a technological operation in which plastic material used to fill with the highly or ultra-filtered sterile preparation is sealed in a sequence of continuous single operating machine with controlled sterile environment. The BFS technology is robust and modern aseptic process and it is recognized by regulatory bodies for the inherent operational process of aseptic type production. In this process the packaging design should be in uniform size and shape and the operating cost of BFS is low comparatively and with high degree of assurance in sterility. The personnel requirement for the handling of machine is less and it occupies less space. Some of the polymers are used in BFS process is polypropylene or high and low-density polyethylene polymers are most commonly used in the process. BFS product are very flexible so it very helpful and also useful in emerging drug delivery technology.

Blow - fill - seal process

In the process of BFS Thermo-plastic are used and extruded in the form of tubular shape. The parison is cut and it closes the mold when the tube reaches the appropriate length. The topmost part of the parison is fixed with a holding jaws and the lowermost part of the parsion is pinched. Then the mold is taken into the filling chamber, and then the nozzle assembly is shifted down into the parision upto the nozzle produce a seal with the neck of the molding. When the vacuum is passing on mold-side then the container sealing is to be done and supply filtered sterile air into the container. Then nozzles are taken back to its initial position. Filling process is completed by container sealing, and then upper part of the container is semi-molted. And the mold is removed then the BFS container is exited through conveyer process. Then the process is continued to produce another BFS container and finally the filled container is tested according to their specifications. It takes nearly 11 to 15 seconds to complete the whole cycle and the amount of liquid filling is depends on the container design in Figure 1.

Advantages of BFS Technology

1. Blow fill seal technology requires less personnel involvement and more vigorous method for sterile pharmaceuticals.

2. Prefabrication process like sterilization and cleaning of containers and closures is not required. Sterility is maintained in the Blow Fill Seal machine as it is required for filling.

3. Transportation and material storage cost is comparatively lesser.

4. The technology allows the custom-designed containers and degree of high quality with tampered evident in a various shapes and sizes (Charles, 2004).

Child resistance packaging

A CR folding carton has die-cut slots on the one finish flap that align. Use die cut tabs to lock the flap within the correct position within wall of the carton. The gap of carton needs a die-cut key to be aloof from the carton's external panel. The essential slides into the slots and pushes the tabs right down to unleash the top flap. Packaging material involves polypropene (PP) or cardboard poly-coated (Forcinio, 2019).

To maximize complete character on packages, the cap may be written in seven colors. The absence of a paper layer reduces the difficulty connected with wet absorption and will increase the time the fabric may hold on.

Prefilled Syringes

Prefilled syringes are an acceptable parenteral product administered by syringes that make more effective and very easy to handle the product and with a good accuracy.

New packaging types on the upswing

Now a days there is a high demand for the pre filled syringes and new project are not limited for the small batches, but pre-sterilized syringes are in the line of high outputs. Pre sterilized packaging are turning from niche products to engaging alternatives for pharmaceutical industries.

Tray and nest systems are the maximum difference between in these systems. Trays are exactly used for standard bulk filling operation. The nest is used for prefilled syringes with machines, and also automated bags and tub opening (Mirror, 2019).

Ampules and Blister packaging

The marketing value for the ampoules and blister packaging is up to USD 12.83 billion in the year of 2019 and also have the expectation to reach up to USD 20.9 billion by 2025. Blister packaging and Ampoules have the same benefits in terms of dosage.

The expanding is required for the product safety through tamper-evident packaging from consumers, regulatory companies, and manufactures have been instrumental in the assuming of ampoules and blister packaging across the pharmaceutical & food industry. As per the energy source outlook 2018 the percentage of the population above 65 years of age is expected to cross 14% by the year 2025 from over 10% in 2016 (Intelligence, 2019).

Ampoules are small glass vessels in that WFI are hermetically sealed. An ampoule has a fine neck in between a cylindrical body and a tapering tip.

HisafeTM ampoules are prepared by pre‑fragilized operaion like SafeCutTM OPC ampoules and SafeBreaKTM color ampoules for free opening by physicians without any damage or without a need of a cutter. SafeCutTM ampoules open at breaking point to give a clean cut. SafeBreakTM ampoules are manufactured with color band on the neck which is used to open the ampoules by hand (Zadbuke et al., 2013).

Unit Dose and Vials

A unit dose is also called as single dose medication to the patient intraveniously. It is a single dose of package in the form of non refillable container. It is preferentially used by physcians, hospitals and nurses etc. and this type of packaging is easily identified and easily returned to pharmacy if the medicine is dropped (Wisegeek, 2019).

Twist‑Tip™ single‑dose vial includes a plastic crush‑bulb with a vital twist‑off tab. If it is opened once, the vial’s matters can be allotted through the opening by pouring. This single dose vials are used in medical devices packaging (in vitro diagnostics: buffers, reagents), oral health care (tooth conditioners, disinfectants, anesthetic, dental materials, pharmaceuticals, ultrasonic cleanser concentrate), personal care products and cosmetics and veterinary (medicines, topical applications) (Healthcarepackaging, 2019).

Conclusions

In the period of globalization, it might be a challenge for the packing trade, because the years ahead would witness the gap of the worldwide channels, and to compete with the international standards, it's required that packing trade promotions, in addition to analysis have an all-inclusive approach to packing that would exceed practical side of packing. Presently, only a few pharmaceutical industries pay time and cash on Research and Development (R and D) in wrapping. The obtainable standard packages don't serve the aim of providing security in contradiction of forging and quality, and therefore the trade looks to be lethargic in accepting the methodological advances within the packing, in all probability on account of the preventative price issue. As packing trade is directly or indirectly concerned within the drug producing method, it becomes morally obligatory to know and incorporate scientific strategies in packing. The pharmaceutical packing trods on the verge of innovative growing, provided the needs of the merchandise, its safety, price and patient suitability is taken into thought to create brand identity.