PHARMACEUTICAL PACKAGING

Pharmaceutical packaging can be defined as the economical means of providing presentation, protection,
identification , information, convenience ,compliance , integrity and stability of the product .

Function of pakaging

• Product Identification:- Packaging greatly helps in identification of products.

• Product Protection:- Packaging protects the contents of a product from spoilage, breakage, leakage, etc.
• Facilitating the use of product:- Packaging should be convenience to open, handle and use for the
consumers.
• Product Promotion:- Packaging is also used for promotional and attracting the attention of the people
while purchasing.

Types of packaging

Primary packaging - is the material that first envelops the product and hold it. This usually is the smallest
unit of distribution or use. Ex. Aerosol spray can, blister packs, bottle

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

Tertiary packaging - is used to bulk handling and shipping. Ex. Barrel, container, edge protector

Material used for packaging

- Glass - Plastics
- Rubbers - Paper/card boards
- Metals

GLASS:
Glass has been widely used as a drug packaging material

• Advantages
-They are transparent. - they have good protection power.
-They can be easily labelled. - Economical
-Variety of sizes and shapes

• Disadvantages
-Glass is fragile so easily broken. - Release alkali to aqueous preparation

Composition of glass
-Sand (silicon dioxide) Soda ash (sodium carbonate) Limestone (calcium carbonate) Cullet (broken glass)
- aluminium, boron, potassium, magnesium, zinc, barium,
-Amber: light yellowish to deep reddish brown, carbon and sulphur or iron and manganese dioxide ---
Yellow: Compounds of cadmium and sulphur
-Blue: Various shades of blue, cobalt oxide or occasionally copper (cupric) oxide
-Green: iron oxide, manganese dioxide and chromium dioxide

Manufacturing of glass :

The four basic processes used in the production of glass are:

- Blowing uses compressed air form the molten glass in the cavity of metal mold.
- In drawing , molten glass is pulled through dies or rollers that shape the soft glass.
- In pressing mechanical force is used to press the molten glass against the side of a mold.
- Casting uses gravity or centrifugal force to cause molten glass to form in the cavity of mold.

Type of glass

• Type I—Highly resistant borosilicate glass

• Type II—Treated soda lime glass
• Type III—soda lime glass
• NP—soda glass (non parenteral usage)

Type I-borosilicate glass

- Alkalinity is removed by using boric oxide to neutralized the oxide of potassium and sodium
- It is highly resistant glass. It has high melting point so can with stand high temperatures.
- It is more chemically inert than the soda lime glass
- It can resist strong acids,alkalies and all types of solvents. Reduced leaching action.

Uses
- Laboratory glass apparatus. - For injection and water for injection.

Type II-treated soda lime glass

- Type II containers are made of commercial soda lime glass that has been dealkalized or treated to
remove surface alkali .
- The de-alkalizing process is know as sulphur treatment.
- Sulfur treatment neutralizes the alkaline oxides on the surface, rendering the glass more
chemically resistant.

Uses: Used for alkali sensitive products. Infusion fluids, blood and plasma. Large volume container.

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
- Less weight than glass, - flexible
- Variety of sizes and shapes
- Essentially chemically inert, strong, rigid Safety use, high quality, various designs

Disadvantages : Absorption permeable to moisture

Types of plastic

• Thermosetting type – When heated they may become flexible but they do not become liquid
e.g. Urea formaldehyde (UF),Phenol formaldehyde ,Melamine formaldehyde (MF), Epoxy resins

• Thermoplastics type- On heating they are soften to viscous fluid which harden again on cooling.
e.g. Polyethylene{HDPE – LDPE}, Polyvinylchloride(PVC),Polystyrene Polypropylene, Nylon(PA),
Polyethylene terepthalate(PET) ,

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 made into rigid unbreakable containers by impact extrusion.
- They are light in weight compared to glass containers.
- Labels can 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 nature

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

RUBBER:
Rubber is used mainly for the construction of closure meant for vials, transfusion fluid bottles, dropping
bottles and as washers in many other types of product.

Butyl rubber
Advantages:
- Permeability to water vapour .  Water absorption is very low.
- They are relatively cheaper compared to other synthetic rubbers.
Disadvantages:
- Slow decomposition takes place above 130 ▫ C.
- Oil and solvent resistance is not very good.

Nitril rubber
Advantages : Oil resistant due to polar nitrile group. Heat resistant.
Disadvantages: Absorption of bactericide and leaching of extractives are considerable.

Chlorprene rubber :
Advantages: Oil resistant. heat stability is good.

Silicon rubber:
Advantages:
- Heat resistance.
- Extremely low absorption and permeability of water.
- Excellent aging characteristic.

Disadvantages: - They are very expensive.

TAMPER RESISTANT PACKAGING:

- The requirement for tamper resistant packaging is now one of the major considerations in the
development of packaging for pharmaceutical products.
- Tamper resistant package is one having an indicator to entry in which, if missing, can reasonably
be expected to provide visible evidence to consumers that tampering has occurred
 - FDA approves the following configurations as tamper resistant packaging: Film wrappers, Blister
package, Strip package, Bubble pack, Shrink seals, and bands Oil, paper, plastic pouches, Bottle
seals, Tape seals, Breakable caps, Aerosol containers

Film wrapper
- Film wrapping has been used extensively over the years for products requiring package integrity
or environmental protection.

It is categorizes into following types:

- End folded wrapper - Fin seal wrapper
- Shrink wrapper

End folded wrapper

- The end folded wrapper is formed by passing the product into a sheet of over wrapping film,
which forms the film around the product and folds the edges in a gift wrap fashion.
- The folded areas are sealed by pressing against a heated bar. The materials commonly used for
this purpose are cellophane and polypropylene.

Fin seal wrapper

- The seals are formed by crimping the film together and sealing together the two inside surfaces of
the film, producing a fin seal.
- Fin sealing is superior than end folded wrapper With good seal integrity the over wrap can
removed or opened by tearing the wrapper

Shrink wrapper
- The shrink wrap concept involves the packaging of the product in a thermoplastic film that has
been stretched and oriented during its manufacture.
- An L shaped sealer seals the over wrap
- The major advantage of this type of wrapper are the flexibility and low cost of packaging
equipment

BLISTER PACKAGE:
- Blister package provides excellent environmental protection, and efficacious appearance.
- It also provides user functionality in terms of convenience , child resistance and tamper resistance
- The blister package is formed by heat softening a sheet of thermoplastic resin and vacuum
drawing the soften sheet of plastic into a contoured mold .
- After cooling the sheet is released from the mold and proceeds to the filling station of the
machine. It is then lidded with heat sealable backing material
- Peel able backing material is used to meet the requirements of child resistance packaging.
- The material such as polyester or paper is used as a component of backing lamination.
- Materials commonly used for the thermo formable blister are PVC, polyethylene combinations ,
polystyrene and polypropylene.

STRIP PACKAGE
 - A strip package is a form of unit dose packaging that is commonly used for the packaging of
tablets and capsule .
- A strip package is formed by feeding two webs of a heat sealable flexible through heated
crimping roller.
- The product is dropped into the pocket formed prior to forming the final set of seals. A
continuous strip of packets is formed in general.
- The strip of packets is cut into desired number of packets.
- Different packaging materials used are: paper/polyethylene/foil/PVC.

BOTTLE SEALS
- A bottle may be made tamper resistant by bonding and inner seal to the rim of the bottle in such a
way that the product can only be attained by destroying the seal .
- Typically glassine liners are two ply laminations use in two sheet of glassine paper bounded
together with wax or adhesive
- For pressure sensitive inner seals pressure sensitive adhesive is coated on the surface of the inner
seal as an encapsulated adhesive.

TAPE SEALS
- It involves the application of glued or pressure sensitive tape or label around or over the closure
of the package which is to be destroyed to obtain the product.
- The paper used must often is a high density light weight paper with poor tear strength.

BREAKABLE CAPS
- Breakable closures come in many different designs.
- The roll-on cap design of aluminium shell used for carbonated beverages.
- The bottom portion of the cap is rolled around the bottle neck finish.
- The lower portion of the cap blank is usually perforated so that it breaks away when the cap is
unscrewed. The bottom portion of the closure has a tear away strip.

SEALED TUBES
- Collapsible tubes used for packaging are constructed of metal, plastic or lamination of foil, paper
and plastic.
- Metal tubes are still used for products that required high degree of barrier protection
- Most of these are made of aluminum .
- Extruded plastic tubes are widely used for products that are compactable and limited protection of
plastic.

Quality Assurance Aspects Of Packaging

• To ensure that patients and consumers receive high-quality drugs, the quality management system
must take the following considerations into account if the required quality of packaging is to be
obtained:
- the requirements of the national authorities and the relevant legislation
 - the product - the production process
- the manufacturers’ internal policies (safety, marketing, etc.).

• Bad packaging which is the result of deficiencies in the quality assurance system for packaging can
have serious consequences, and packaging defects can create problems that may result in drug recalls.
Such defects may include breakage, and problems relating to printing or inks, or errors on labels and
package inserts (patient information leaflets). The use of GMP and quality control will prevent the
release of a defective medicinal product.

• Packaging processes and equipment need validation/qualification in the same way as any other part of
processing within a pharmaceutical facility.

Sampling and testing of packaging materials

• Sampling
Sampling is used;
- To check the correctness of the label, packaging material or container reference, as well as in the
acceptance of consignments,
- Detecting adulteration of the medicinal product, obtaining a sample for retention, etc.
- The sampling procedure must take into account the homogeneity and uniformity of the material
so as to ensure that the sample is representative of the entire batch.
- The sampling procedure should be described in a written protocol.
-
• Testing programme

Quality control tests are intended to check the identity of the material concerned. Complete
pharmacopoeial or analogous testing may also be carried out, as may special tests, where necessary. All
written specifications for packaging materials and containers should include the nature, extent and
frequency of routine tests. Routine tests vary according to the type of material and its immediate
packaging, the use of the product, and the route of administration. Nevertheless, such tests usually
include the following:
- visual inspection (cleanliness, defects)
- tests to identify the material
- dimensional tests
- physical tests
- chemical tests
- microbiological tests
-
PACKAGE VALIDTAION

Package validation involves two separate validations:

1) The design validation of the package as a component of the device Design validation uses evidence to
establish what design specifications will conform with the user needs and the intended use and
2) The process validation of the packaging process. Process validation establishes by objective evidence
that a process consistently produces a result or product that meets predetermined specifications.