Packaging industry worldwide is estimated at a net worth over $280 billion, where consumer healthcare products and pharmaceuticals constitute a substantial fraction of about eight per cent ($22.4 billion) of the total packaging industry. A few decades ago, drug manufacturers considered packaging of formulation as the final step in production-line but now the packaging process is viewed inherently during the development phase to optimize product specifications and dose regimes.

Consumers in the United States are very brand conscious for quality of pharmacy; and a company’s brand is a statement of reliability from the producer. Drug packaging is a core element of marketing mix through which manufacturers differentiate their products from those of their competitors.

As new regulations on packaging focus on increased stability and extended life of drug formulation, printing or labeling standards protect patient’s compliance for specific tablet or capsule offered by some companies. Packaging is a means to impart protection of goods for storage or export whereas labels identify goods intended for immediate sales or transport.

Drug packaging can be broadly classified into four categories – primary, secondary, tertiary and quaternary packaging. Primary packaging is a material that envelops the product, impart barrier from immediate environment to protect its activity and holds it. Secondary packaging is outside the primary packaging that group primary packs together. Tertiary packaging is used for bulk storage and transportation, whereas quaternary packaging utilizes huge containers for shipment to another territory or port.

A primary pack is a design to ensure minimum volume (optimized product), maximum stability to enable ease of identification of product specifications (size, shape, color, volume, strength) and facilitates ease in handling or dispensing product for intended use. A primary pack imparts physical barrier to the product from external environment that protects from air oxidation, moisture, mechanical damage, chemicals, microbial contamination, dust and other environmental toxins.

Primary and secondary packaging facilitates ease of handling and dispensing for a single unit at actual point of sales whereas tertiary packaging varies with the amount of bulk product and type of formulation for transportation and storage. To conclude, packaging fulfills multiple objectives of physical protection from mechanical shock,     vibration, electric discharge or temperature as well as ensures freshness, sterility, cleanliness and prolonged life.

This report analyzes various packaging modules available to the pharma industry for packing tablets and capsules using variety of materials and their mechanism of operation. Packaging machines such as filling machine, sealing machine, wrapping machine, strapping machine, and cleaning, drying or sterilizing machines completes this final step of primary packaging in drug manufacturing process, followed by labeling and coding of packaged product. Packaging machines offer advantage of reduced labor costs, increased efficiency and reliability on the quality of packaging. Machines can be operated manually or readily automated using industrial automation devices.

Packaging materials
Polyvinyl Chloride (PVC): PVC is the most commonly used packaging material due to its low cost, very small pore size (less than 20 – 25 microns), flexibility, rigidity and ease of thermoforming. Thermoformed PVC sheets are widely acceptable for blister packaging of oral pharmaceutical doses in dry state. PVC sheet of thickness 250 microns or 0.25 mm, free from plasticizers is ideally suitable for thermosealing or blister packaging of tablets because it offers structural rigidity and physical protection for pharmaceutical dosage form. Typical values for water vapor transmission rate (WVTR) for 250µ PVC film is around 3.0 g/m2/day measured at 38 °C and 90% relative humidity (RH); and, oxygen transmission rate (OTR) is around 20 mL/m2/day. PVC sheet can be colored with pigments to impart UV protection. However, PVC offers some disadvantages of moisture ingress or oxygen diffusion in presence of high moisture or high oxygen environment. US, British, European and Indian pharmacopeia contain specific guidelines on use of PVC, PV dichloride (PVDC) and additives for their use as packaging material for specific formulations like tablets, capsules and powders or their use as containers.

Polychlorotrifluoroethylene (PCTFE): PCTFE is modified polyethylene (PE) that prevents entry or exit of moisture from laminated surface. Pharmacopeia standards indicate lamination of 15 – 150 microns thickness to 250 microns PVC to impart physical protection to packaged formulation. Typical WVTR values noted are 0.06–0.40 g/m2/day and lamination also enables formation of deep rigid cavities on thermoforming.

Cyclic olefin copolymers (COC) or Cyclic olefin polymers (COP): COC is an amorphous resin having good thermoforming properties, particularly used with other semi-crystalline resins like polypropylene (PP), polyethylene (PE) or glycol modified polyethylene terephthalate (PETg) in blister packaging units as thermoforming enhancer. Multilayered PVC blister films with COC, PVDC, PCTFE, PP or PET can be prepared via co-extrusion or lamination giving even low WVTR values range from 0.20 to 0.35 g/m2/day at 38 °C and 90% RH. Unlike PVC and other pharmaceutical resins, COC resins being composed solely of carbon and hydrogen do not contain chlorine in their molecular structure therefore offer thermosetting advantages over other resins.

Aluminum: Aluminum – aluminum, aluminum-paper, aluminum – PET or aluminum – clay are typically used combinations that offer advantage of light weight, material opacity, low WVTR, low OTR for lidding the blister pack. The lid is the base structure of primary pack having caliper or thickness ranging from less than 1 mm to maximum 2 mm, depending upon the weight of the product, which allows ease in dispensing of tablet or capsule from the pack. The lid is the base or main structural component upon which final blister package is built. The surface of the lid material must be compatible with the thermosealing and coating process. Clay coatings added to the lid material enhance printing image. Various shapes, styles, weights, sizes can be produced with annealed foil or laminated tissue for lid. Lidding material usually carries a seal coat on product facing side particularly towards the end that needs to be sealed.

Seal is accomplished with the help of sealing liquor, with predefined settings for strength and tolerance.

Cellulose polymers: Cellulose or lignin polymers are constituents for paper based products that form wide variety of products, which depend upon the concentration of pulp and laminations. Paper based materials find applications in lidding of primary packs with combination of aluminum or PET and mostly used for secondary and tertiary packaging of unit products. Paper cardboards, corrugated boxes and paper packaging are ideal for powder products in dry state and must be kept in an environment free of moisture.  

Types of packaging for tablets
Blister packaging is most common and widely accepted world-over as primary pack of tablets or capsules due to its efficacy and safety considerations. Alternative to blister packs is strip packaging or glass vial with a sealed cap. The primary component of a blister pack is a thermoplastic material, thermoadhesive solvent, and lid. A blister pack has a preformed pocket or cavity of thermoplastic material like PVDC that is heat sealed to a composite lidding material like aluminum/paper/PET with the help of adhesive. Another type of blister packs made by cold forming use lidding material such as aluminum foil as double-web component to create a cavity by cold stretching, which holds the capsule.

Blister packs are commonly used as unit-dose packaging for pharmaceutical tablets, capsules or lozenges.  It is useful for protecting drugs against external factors, such as humidity and microbial contamination for extended period of time as well as offers a degree of mechanical resistance from physical tampering. Opaque blisters protect light-sensitive compounds from UV rays. They offer an advantage of dispensing tablet or capsule by means of pressing it out with the thumb. Number of doses can be precisely controlled using blister pack because it contains individual units of tablet or capsule in each cavity.

The patient can handle blister pack and store more easily over conventional packages in small paper bags or glass vials. It prevents mixing of different tablets and enables ease of recognition by the patient to administer proper dose.

Blister packs are convenient and cost effective as they offer optimization of dose and manufacturing process thereby utilizing resources effectively. Blister packs have widely extended their application in dispensing medical equipments, kits, food, and other dry consumables due to extended product protection, tamper resistance, accidental misuse and patient compliance. Tablet fillers help fill blister cavities by counting unit number rather weight in each unit. Ideally weight, strength and other specifications of unit is controlled precisely in production process while making a tablet. Hopper filler can be set-up to permit scanning tablets or candy count.

Strip packaging is an alternative form for unit dose packing that encloses the article between two webs of material so that each unit is contained in a separate compartment. Strip packaging is a high speed packaging machine suitable for variety of products like tablets, capsules, pills. High quality sealing is achieved through precise temperature controllers, adjustable sealing pressure on rollers, rugged and precise construction. It is suitable for heat sealable coated films like paper alloy, aluminum films, glassine, cellophane with adjustable cutting arrangements for knurling, noiseless, trouble free and smooth operation. Web materials are fed between heat rollers with circumferential cavities of typical size, depth, shape and thickness. The material to be packed is fed from feed hopper through channels that drop between the web to meet at the roller cavity.

 Thermosealing forms a pocket around the content. Strip design is basic, emerging units that are invariably rectangular or square strip. Packet can be round, oval or square of different diameter, size and shape. High speed tablet strip packaging can be fully automated for large quantity of package, with high work efficiency. Adjustable film feeding system, pin-hole device and conveying tables can meet requirements of different products. Length of the film or strip can be controlled or automated, suitable for wide variety of packaging materials. Tight perforations or tight pockets result in wrinkles in the seal. If seal area is likely to wrinkle or crease then wider pocket seal of width 5 mm or above is considered.

 Sealed packets can be withdrawn at random intervals for inspection – exposed to radiation tests, water test, and vacuum test. Advantages of strip pack are that contents individually protected with increased shelf life like blister packs. Strip of more than one item can be prepared in combination. It’s compact design provides material optimization and resistant to child tampering. Its disadvantages are that machine occupies more land, high cost variations depend upon the article packaging. The main difference between a strip pack and blister pack is that in strip pack cavity is formed around the tablet at a time when it is dropped to the sealing area between sealing moulds unlike preformed cavities of thermoplastic material in blister pack.

Mechanism of sealing
Heat seal (Thermosealing): Thermoplastic materials can be joined using heat or join dissimilar materials with at least one layer being thermoplastic. The strength of seal depends upon the material quantity and thickness. Thermosealing is a process of sealing thermoplastics using heat and pressure. There are various mechanisms of applying heat and pressure to the material, which depends on the application of product. Plastic bags used in medical industry, food packaging, bioengineering applications are made of multitude variants of foils, filter media with different proportion of thermoplastics and laminates through direct contact. Direct contact sealing employs constantly heated die or sealing bar to apply heat to a specific contact area or sealing path to weld thermoplastics together.

 The sealing unit may additionally contain seal connectors, thermally activated adhesives, film media, foil or clay typically in machines employed for electronic devices, construction modules or packaging consumer durables. Hot bar sealers have a heated tool (iron bar, die) kept at constant temperature. The bar can vary in configuration and coating to prevent it from sticking to the plastic material. Continuous heat sealing utilize moving belt over the heating element. Special adhesives are used to strengthen the bond between strips or beads at the point of joining. Adhesives can be pre applied during the manufacturing process or at the point sealing using one or more mechanisms. Induction sealing is a type of non-contact sealing used to seal inner cap of bottles.

Plastic welding is a type of heat seal for semi-finished plastic materials to unite the softened surfaces of materials with the aid of heat. Plastic welding of thermoplastics is accomplished in three sequential stages, namely surface preparation, application of heat and pressure, and cooling. The Vertical form fill sealing machine (VFFS) is a type of automated assembly-line product packaging system used in packaging industry. The machine constructs plastic bags out of a flat roll of plastic film, while simultaneously filling the bags with product and sealing the filled bags. Both solids and liquids can be bagged using this packaging system. A good seal is the result of time, temperature and pressure for correct material and clean operation. Testing standards measure the strength of heat seals in packaged unit to determine the ability of completed packages to withstand specified pressure or vacuum. Several diagnostic methods are available to determine the ability of a sealed package to retain its integrity, barrier characteristics, and sterility. The efficacy of heat seals is often detailed in governing specifications, contracts, and regulations.

Molding or blister process: In thermoforming or blister process a plastic film or sheet unwounds from the reel and guided though a pre-heating station on the blister line. Plates (upper and lower) at this station are pre-heated to a temperature where plastic softens and become pliable. The warm plastic on arrival at the forming station forms blister cavity into a negative mold under application of large pressure (4 to 8 bars). The mold is allowed to thermoset (cooled) until plastic becomes rigid again and maintains its shape when removed from the mold. Plug-assist feature can be employed to obtain different shapes on warm film. This feature results in blister cavity with more uniform wall distribution and is used typically when the cavity size and shape is larger than size of tablet and capsule.

Heat-seal coatings for blister packages is the most critical component in the entire system as it binds the blister thermoplastic to lid material.

The appearance and physical integrity of the package depends upon the quality of the heat-seal coating. A solvent- or water based coating can be applied to rolls or sheets of printed paperboard using rollers, flexographic methods, knives or sprays with optimum coating weight that would result in optimum heat sealing. A successful heat seal coating for blister packages must exhibit good gloss, clarity, abrasion resistance, and hot tack and must seal to various blister films. A relatively low heat-seal temperature is desirable for rapid sealing and to prevent heat distortion of the blister film. Specifically, the sealing strength must fall within predetermined tolerance limits and must be suitable for push-through or peel-off opening.

Cold forming or Cold form foil (CFF) blisters: Lid sealing process employs an aluminum-based laminate film pressed against the blister mold by means of punch like stamp. The aluminum lid elongates slightly and maintains the formed shape. The principal advantage of cold forming blisters is that use of aluminum based materials that offer near complete barrier to water and oxygen thereby increasing the shelf-life of the drug product (extended expiry date). However, it is disadvantages in terms of slow production speed compared to thermoforming and lack of transparency of the pack. Large size blister cards are practically impossible.

The lid material is the base or main structural component upon which blister pack is built. It is selected according to the size, shape, and weight of the product as well as the style of the package to be produced. An important consideration for lid is heat seal and base printing. The heat sealing primer ensures optimum adhesion of thermoplastic blister to the aluminum foil. Sealing coats can then be matched to the formed laminated films. Perforations along the sealed seam prevent pealing of the film at once. In paper – aluminum combinations the paper amounts to 40 – 50 b/sq m. & the thickness of aluminum typically is in range 0.28–0.48 pm. Thickness of aluminum can differ according to country specifications. Lidding material made of a paper/PET/aluminum laminate is often called peel off–push through foil, a kind used in the United States.