Packaging.ppt

Introduction:



Pharmaceutical packaging can be defined as the economical

means of providing presentation, protection, identification ,

information, containment, convenience ,compliance ,

integrity and stability of the product

.

The materials selected must have following

characteristics:

 They must protect the preparation from environmental conditions.  They must not be reactive with the product.

 _{They must not impart to the product tastes or odors.}

 Must be non toxic.

 They must be “FDA” approved.

 They must meet applicable tamper – resistance requirements.

 They must be adaptable to commonly employed high-speed packaging

Types of containers:

Containers are divided into following types on the basis of their utility :

Well – closed containers: A well-closed container protects the contents

from loss during transportation,handling,storage or sale.

Single dose containers : These containers are used to supply only one of

Multi dose containers: These containers allow the withdrawal of

dose at various intervals without changing the strength, quality or purity of remaining portion. these containers hold more than one dose and are used for injectables. E.g. vials

Light-resistant containers: These containers protect the medicament from harmful

Air-tight containers: These are also called hermetic containers. These containers

have air-tight sealing or closing. These containers protect the products from dust, moisture and air. Where as air-tight sealed containers are used for injectables,air-tight closed containers are meant for the storage of other products.

Aerosol containers: These containers are used to hold aerosol products. These

TYPES OF PACKAGING :

Primary packaging is the material that envelopes 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.

_{Secondary packaging}

_{Tertiary packages:}



QUALITIES OF GOOD CONTAINER

The container must be neutral towards the material which is stored in it.

The container must not interact physically or chemically with the substance which it holds.

It should help in maintaining the stability of product against the environmental factors which causes its deterioration.

It should be made of materials which can withstand wear and tear during normal handling.

It should be able to withstand changes in pressure and temperature.

MATERIALS USED FOR MAKING OF CONTAINERS:



GLASS-e.g.bottles,vials,ampules,syringes,i.v containers, aerosol containers.



_RUBBER-

e.g. closures, caps,vialswrapers,plungers.



Metals

Paper or cardboard

-e.g

.

Composition of glass:

_{Glass is composed principally of sand, soda ash, lime stone and}

cullet.

Sand is almost pure sillica,soda ash is sodium carbonate, lime stone is calcium carbonate.

_{Cullet is broken glass that is mixed with the batch and acts as}

fusion agent for the entire mixture.

Manufacture of glass:

The four basic processes used in the production of glass

are:-1.Blowing uses compressed air to form the molten glass in the cavity of metal mold.

2.In drawing, molten glass is pulled through dies or rollers that shape the soft glass.

3.In pressing mechanical force is used to press the molten glass against the side of a mold.

TYPES OF GLASSES:

Type I-borosilicate glass

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.}

Type II-treated soda lime glass

Type II containers are made of commercial soda lime glass that has been dealkalised or

treated to remove surface alkali.

The de-alkalizing process is know as sulfur treatment.

Sulfur treatment neutralizes the alkaline oxides on the surface, rendering the glass more chemically resistant.

Uses:

Type-III regular soda lime glass

Containers are untreated are made of commercial soda lime glass of average are better than average chemical resistance.

It contains high concentration of alkaline oxides and imparts alkalinity to aqueous substances.

Flakes separate easily.

USES:

Type NP-general purpose soda lime glass

Containers are made of soda lime glass supplied for non parental products, intended for oral or topical use.

USES:

FOR ORAL USE.

Test Method Glass type Over flow capacity

O.O 2 M H₂SO₄ required (ml)

Powdered Glass test

Type I All 1

Water

attack test

Type II ≤ 100 > 100

0.7 0.2

Powdered Glass test

Type III All 8.5

Powdered Glass test

Type IV /NP All 15

ADVANTAGES OF GLASS:

They are quite strong and rigid.

They are transparent which allows visual inspection of the contents.

They are available in various shapes and sizes.

They can withstand the variation in temperature and pressure during sterilization.

They are economical and readily available.

They can protect the photosensitive medicaments from light during their storage.

DISADVANTAGES OF GLASS:

_{They are brittle and break easily.}

_{They may crack when subject to sudden changes in temperatures.}

PLASTIC CONTAINERS:

Plastics are synthetic polymers of high molecular weight.

Plastics as packaging have proved useful for a number of reasons,

including the ease with which they can be formed, their high quality and the freedom to design.

PLASTIC ARE OF TWO FROMS

:

1.Amorphous plastic.

2.Crystalline plastic.

AMORPHOUS PLASTIC:

_{They give good transparency.}

_{They are hard but posses little brittleness.}

_{They are more permeable to gases and vapour.}

CRYSTALLINE PLASTICS:

For photo sensitive drugs this type of plastics are selected.

They are opaque.

They are more flexible.

_{They are less permeable to gases and vapour.}

Plastic containers for pharmaceutical products are primarily

made from the following polymers:

 _polyethylene

 polypropylene

 poly vinyl chloride

 polystyrene

 polymethyl methacrylate

 _{amino formaldehyde}

Thermoplastic type :

-On heating, they are soften to viscous fluid which hardens again on cooling.

e.g. polyethylene ,PVC ,Polystyrene, polypropylene, Polyamide, Polycarbonate.

Thermosetting type

:-When heated , they may become flexible but they do not become liquid.

1) Polyethylene:

 _{Its is flexible, very light but tough plastic.}

 _{It is impermeable to water vapour and does not deteriorate with age unless it is}

exposed to sunlight for long time.

 _{It has permeability to certain oils and preservatives.}

 _{Its melting point being in the range of 110}0 _{to 150}0_c

 _{It has high melting point and can sterilized by autoclaving.}

 _{It is divided into 1. HDPE} (HIGH DENSITY POLYETHYLENE )

2. LDPE ( LOW DENSITY POLYETHYLENE )

 _{HDPE : Inert, low cost, tough in nature.}

 _{LDPE : Inert, great resistant to gases, low cost.}

POLYVINYL CHLORIDE (PVC ):

It is less flexible , heavier and more permeable to water vapour as

compared with normal polythene.it has high clarity and not effected

POLYMETYL METOCARYLATE(PMMA):

It is hard , strong but light, transparent plastic.

It softens at about1000c.

POLYSTYRENE:

It is a hard, rigid , light material.

It can be easily molded into any shape.

POLYPROPYLENE:

It is similar to high density polythene.

It is very light and heat resistant.

Its melting point is 1700c

It has high melting point and can sterilized by autoclaving.

POLYCARBONATE:

It is transparent, has high impact strength and very good heat resistance.

ADVANTAGES OF PLASTIC:

They are light in weight and can be handled easily.

They are transported easily.

They are unbreakable.

They available in various shapes and sizes.

DISAVANTAGES OF PLASTIC:

They are permeable to water vapour and atmospheric gases.

They are poor conductor to heat.

They may absorb chemical substances, such as preservative for solutions.

DRUG-PLASTIC CONSIDERATIONS

A packaging system must protect the drug without altering the composition of the product until the last dose is removed.

Drug-plastic considerations have been divided into five categories:

1.Permeation

2.Leaching

3.Sorption

4.Chemical reaction

Permeation

:

It is the transmission of gases, vapors or liquids through plastic packaging material.

Permeation of water vapor and oxygen through plastic wall into the drug is a major problem is the dosage form is sensitive to hydrolysis and

oxidation.

The volatile ingredients might change when stored in plastic containers

Leaching:

Some plastic containers have one or more ingredients added to stabilize

it, these may leach into the drug product.

Problems may arise with plastics when coloring agents are added in small quantities to the formula.

Sorption:

This process involves the removable of constituents from the drug product by the packaging material.

The therapeutic efficacy of the product may be reduced due to sorption.

Chemical reactivity

:

Certain ingredients in plastic formulations may react chemically with one or more components of the drug product.

Modification:

The physical and chemical alteration of the packaging material by the drug product is called modification.

Some solvent systems found to be considerable changes in the mechanical properties of the plastics.

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.

DISADVANTAGES:

They are expensive.

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.

Tin:

Tin containers are preferred for food, pharmaceuticals and any product for which purity is considered.

Aluminum:

Aluminum tubes offer significant savings in product shipping costs because of their light weight.

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}

CLOSURE:

A closure is the part of the package which prevent the contents from escaping and allow no substance to enter the container.

Closures are available in five basic designs

1.Screw on, threaded or lug 2.Crimp on(crowns)

Threaded screw cap:

When a screw cap is applied, its threads engaged with the corresponding threads molded on the neck of the bottle.

A liner in the cap, pressed against the opening of the container, seals the product in the container and provide the resistance to chemical and physical reaction with the product.

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.

Unlike the threaded closure, it requires only a quarter turn.

Crown caps:

Roll-on closures

The aluminum roll on cap can be seal securely, opened easily and resealed effectively.

Pilfer proof closures

It is similar to roll on closure but has a greater skirt length.

This additional length extends below the threaded portion and fastened to the basic cap by the series of narrow bridges.

CLOSURE LINERS:

A liner may be defined as any material that inserted in a cap to effect a seal between the closure and the container.

It is of two types:

1.Homogeneous liner

These are one piece liners available as disk or a ring of rubber or plastic.

It can be withstand high temperature sterilization.

2.Heterogeneous liners

These are composed of layers of different materials chosen for specific requirements.

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 vapor .} Water absorption is very low.

_{They are relatively cheaper compared to other synthetic rubbers.}

Disadvantages:

Slow decomposition takes place above 1300C.

NITRILE RUBBER:

Advantages:

_{Oil resistant due to polar nitrile group.} Heat resistant.

Disadvantages:

Absorption of bactericide and leaching of extractives are considerable.

CHLOROPRENE RUBBERS

:

Advantages:

Oil resistant.

SILICON RUBBERS:

Advantages: Heat resistance.

Extremely low absorption and permeability of water. _{Excellent aging characteristic.}

_{Disadvantages:}

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

FDA approves the following configurations as tamper

resistant packaging:

5.Shrink seals and bands

6.Oil, paper, plastic pouches 7.Bottle seals

8.Tape seals

9.Breakable caps

1. 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:

i. End folded wrapper

ii. Fin seal 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.}



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}



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}

BLISTER PACKAGE:

Blister package provides excellent environmental protection, esthetically leasing 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.

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.

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:

BUBBLE PACK

A bubble can be made usually by sandwiching the product between a thermo formable, extensible or heat shrinkable plastic film and a rigid backing material.

SHRINK BANDING

The shrink band concept make use of heat shrinking characteristics of a stretch oriented polymer usually the 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.

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.

Labels made of self destructing papers are available.



BREAKABLE CAPS

Breakable closures come in many different designs.

_{The roll-on cap design of aluminum 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.

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.

AEROSOL CONTAINER

The aerosol container used for pharmaceutical products is usually made of drawn aluminum.

A hydrocarbon propellant in its cooled liquid phase is added to the container along with the product.

A spray nozzle contained in a gasket metal is crimped over the opening of the container.

SEALED CARTONS

Folding paperboard cartons have been used as a secondary package for OTC products.

EVALUATION OF PACKAGING

MATERIALS

TESTS FOR GLASS CONTAINERS:

1) Powdered glass test 2) Water attack test

Preparation of specimen for powdered glass test:

Rinse 6 or more containers and dry them

Crushed in to fragments

place 1 portion in a mortar

Crush further by striking 3 or 4 blows with hammer

Nest the sieves (# 20,40 at least)

Empty the mortar in to sieve 20

Shake the sieves and remove the glass particles from # 20 and 40

Crush them again and sieve them

Spread the specimen on a glazed paper

and remove iron particles with the help of magnet

Wash with 6 portions of 30ml acetone

Dry the contents for 20mins at 140oc

Transfer to weighing bottle and cool in a desiccator

1) POWDERED GLASS TEST: (according to USP volume 27)

Transfer 10gms of prepared specimen in a 250ml conical flask digested previously with high purity water in a bath at 90o _c

Add to conical flask containing 50ml high purity water

Cap all the flasks and auto clave

Adjust temperature to 150o_c

Cold the temperature to 121o_{c for 30mins}

Wash the residue powdered glass(4 times with 15ml purity water)

Add the decanted washings to main portion.

add five drops of methyl red solution.

Titrate immediately with 0.02N sulphuric acid.

Record the volume of 0.02N sulphuric acid.

WATER ATTACK TEST:(USP)

rinse 3 or more containers with high purity water

fill each container to 90%of its over flow capacity

cap all the flasks and autoclave for 60mints

empty the contents and cool the contents in 250ml conical flasks to a volume of 100ml

add 5 drops of methyl red solution

titrate with 0.02N sulphuric acid while warm

record the volume of 0.02Nsulphuric acid consumed

TESTS FOR PLASTIC CONTAINERS

1.Leakage test for plastic containers(non injectables and injectables 1996 IP):

fill 10 plastic containers with water and fit the closure

keep them inverted at room temperature for 24 hrs

2.WATER PERMEABILITY TEST FOR PLASTIC

CONTAINERS(INJECTABLE PREPARATIONS IP

1996):

fill 5 containers with nominal volume of water and sealed

weigh each container

allow to stand for 14 days at relative humidity of 60% at 20-250C

reweigh the container

TESTS FOR RUBBER/RUBBER CLOSURES 1.FRAGMENTATION TEST(IP 1996):

place a volume of water corresponding to nominal volume-4ml in each of 12 clean vials

close vial with closure and secure caps for 16hrs

pierce the closure with number 21 hypodermic

needle(bevel angle of 10 to 140c)and inject 1ml water and remove 1ml air

repeat the above operation 4 times for each closure

count the number of fragments visible to naked eye

2.SELF SEALABILITY TEST FOR RUBBER CLOSURES APPLICABLE TO MULTI DOSE CONTAINERS ONLY(IP 1996):

fill 10 vials with water to nominal volume and close the vials with closures

pierce the cap and closures 10 times at different places with no 21 syringe needle

immerse the vials in 0.1 %W/v solution of methylene blue under reduced pressure

restore the nominal pressure and keep the container for 30 min and wash the vials

MATERIALS FOR CONSTRUCTION OF

FACTORS AFFECTING SELECTION OF

MATERIALS FOR PLANT CONSTRUCTION

 _{3 Types of factors:}

I.Chemical factors.

II.Physical factors.

CHEMICAL FACTORS:

1.Contamination of the product by material of plant lead to instability, decomposition and physiological effect.

_{E.g. presence of traces of heavy metal decompose penicillin.}

_{Stability of vitamins decrease in presence of metallic ions.}

_{The color of esters will change to pale yellow in the presence of iron}

impurities.

2 .The effect on the material of plant by drugs and chemicals.

 Acids, Alkali and Oxidizing agent and tannins may affect the material of construction.

PHYSICAL FACTORS:



Adequate mechanical strength.



Erosion.



Weight.



Ease of fabrication.



Thermal expansion.



Thermal conductivity.



Cleansing.



Sterilization.

STRENGTH

MATERIAL OF CONSTRUCTION

METALS NON-METALS

FERROURS NON-FERROUS IN -ORGANIC _ORGANIC

FERROUS METALS:

oWidely used because of its mechanical strength, abundant availability and lower cost.

CAST IRON:



Cast iron consist of iron with a proportion of carbon.

The properties of iron depends on the amount of carbon present.

They are hard and brittle.

CARBON STEEL OR MILD STEEL:

STAINLESS STEEL:

_{Steels containing 18 % of chromium and 8% of nickel and known as “18/8}

Stainless steel” , have considerable use in the pharmaceutical industry.

_{Chromium and nickel, which makes the steel corrosion resistant.}

_{Stainless steel is stabilized by the addition of titanium, or tantalum.}

_{Minor amount of other elements such as copper, molybdenum and selenium}



PROPERTIES OF STAINLESS STEEL:

Heat resistant.

Corrosion resistant.

Ease of fabrication.

Tensile strength.

NON-FERROUS METALS

ALUMINIUM

ALUMINIUM:

Its is cheap, light in weight and offer good mechanical strength.

Aluminum equipment can be easily fabricated_.

Aluminum can be strengthened by cold working.

Number of modification of aluminum are available.

LEAD:

It has the lowest cost.

Used as collapsible tube material particularly for non-food products such as adhesive inks, paints and lubricants.

Lead tubes with internal linings are used for fluoride tooth-paste.

LEAD ALLOYS AND MODIFICATIONS:

Acid lead and copper leads are used in chemical industries.

Some metals are added to lead for altering properties.

SILVER AND COPPER:

Improve corrosion resistant.

TIN,ARSENIC:

Hardens, steel melting point is low.

Lead lined steel structures are used for the construction

of pipes, valves, vessels designed for operations at high

NON-METAL INORGANIC

GLASS

GLASS STEEL:

_{Glassed steel is cooled to a rigid condition without crystallizing.}

_{It requires special consideration in its design and use.}

_{Glassed steel combines the corrosion resistance of glass with the}

NON-METAL ORGANIC

RUBBER

RUBBER:

_{Used as such lining material for the construction of plants.}

_{Type of rubber:}

I.Natural rubber.

II.Soft-rubber.

III.Hard-rubber.

Plastics are synthetic polymers of high molecular weight.

_{Plastics as packaging have proved useful for a number of reasons,}

including the ease with which they can be formed, their high quality and the freedom to design.

_{Plastic containers are extremely resistant to breakage and offer safety}

consumers

ADVANTAGES OF PLASTIC:

They are light in weight and can be handled easily.

They are transported easily.

They are unbreakable.

They available in various shapes and sizes.

DISADVANTAGES OF GLASS:



They are brittle and break easily.



They may crack when subject to sudden changes in

temperatures.



They are heavier in comparison to plastic

Thermoplastic type

:-On heating, they are soften to viscous fluid which hardens again on cooling.

e.g.

polyethylene ,PVC ,Polystyrene ,polypropylene ,Poly amide ,Polycarbonate.

Thermosetting type

:-When heated , they may become flexible but they do not become liquid.

Phenol formaldehyde ,urea formaldehyde, melamine formaldehyde

BASED ON UTILITY OF PLASTIC

:

Rigid materials.

Flexible materials.

Metallic surfaces.

Plastic cements.

RIGID MATERIALS:

These are phenolic resins with resins various inert filler.

Used in fabrication of number of items.

Light in weight.

Used in gears, pipes ,fittings, ducts, valves, vessels.

FLEXIBLE MATERIALS:

These are thermo plastic materials.

These materials can be rigid or flexible depending upon the amount of plasticizer added.

METALLIC SURFACE:

Plastics of polyethylene or polyvinyl chloride types are used along with plasticizer for the coating of metallic surfaces.

These are used to protect the metal from corrosion.

PLASTIC CEMENTS:

Used for spaces between acid resistant tiles and bricks.

SPECIAL CASE:

Plastics are used as guards for moving parts of machinery.

Packaging is one of the most important part of

pharmaceutical industries .

Product produced is might be of vary good quality at the time production but it is useless if is not able to reach as it is up to end user.

Quality Maintenance is the major role played by

packaging material .Along with that it gives pharmaceutical elegance and convenience to user to product .

Many times the Packaging is may become a ideal unique identification for some of brand in market .Quality control of such important part is also a vary valuable work.

REFERENCES

Packaging materials “ Leon Lachman and Herbert

A. Lieberman”.

Materials of plant pharmaceutical plant construction

“Copper and Gunn's” tutorial pharmacy.

Packaging materials R.M.MEHTA Pharmaceutics-I