PAPER-III

NDDS (PART-I)

Pharmaceutical Packaging

SEMINAR ON PHARMACEUTICAL PACKAGING

GUIDED BY: Dr. R. K. PARIKH

PREPARED BY:M.PHARM SEM- II (2009-10)

DEPT. OF PHARMACEUTICS & TECHNOLOGY L.M.COLLEGE OF PHARMACY AHMEDABAD-09.

M.PHARM SEM-II (2009-10) L.M.COLLEGE OF PHARMACY, AHMEDABAD ² 09

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PAPER-III

NDDS (PART-I)

Pharmaceutical Packaging

Definition: PACKAGING: It is the science, art and technology of enclosing or protecting product for distribution, storage, sale, and use. It also refers to the process of design, evaluation and fabrication of the packages.  PHARMACEUTICAL PACKAGING: It can be defined as means for providing protection, presentation, identification, information, convenience, compliance and compatible unit, which maintain the integrity and stability of the product.

Definition as per USP XXVII: WELL CLOSED CONTAINER: It protects the contents from extraneous solid and from loss of the article under the ordinary condition of handing, shipment, storage and distribution.  TIGHT CONTAINER: It protects contents from the contamination by extr aneous liquid, solid or vapor from loss of the article and from efflorescence, deliquescence or evaporation.  HERMETIC CONTAINER: It is impervious to air or any other gas under the ordinary condition of handing, shipment, storage and distribution.  LIGHT RESISTANT CONTAINER: It protects the contents from the effect of light. A clear and colorless or translucent container may be made light resistant by means of opaque covering.  TAMPER EVIDENT CONTAINER: The container or individual carton of a sterile article intended for ophthalmic or optic use which cannot be used without destruction of the seal.

Role of Packaging: Protection against y Light y Reactive gases y Moisture  Presentation  Identification  Information  Compatible  Convenience
y Microbes y Physical damage y Pilferage y Adulteration

New concept:     
Packaging builds brand identity of the product. Packaging way to differentiate the product with others. Revolution in retail by display of the product. Patient convenience Innovation through pack design Packing that fulfill emotional needs.

Objectives of Packaging: Physical protection: Package may require protection from other things, shock, vibration, compression, temperature.
M.PHARM SEM-II (2009-10) L.M.COLLEGE OF PHARMACY, AHMEDABAD ² 09

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PAPER-III

NDDS (PART-I)

Pharmaceutical Packaging 

Barrier protection: A barrier from oxygen, water vapor, dust is required.  Containment or agglomeration: Small dosages are typically grouped together in one package for reasons of efficient packaging physical handling.  Information transmission: Information on how to use, transports, recycle or dispose of the package or product is often contained on the package or label.  Marketing: The packaging and the labels are used by marketers for the purpose of encouraging potential buyers to purchase the product.  Security: Packages can be made with improved tamper resistance to deter tampering and also can have tampered evident features to help indicate tampering.  Convenience: Packages can have features, which add convenience in distribution, hand ling, display, sale, opening, reclosing, use and reuse.

Importance of Packaging:    
Protect against all adverse external influences that can alter the properties of the product. Protect against biological contamination. Protect against physical damage. Carry the correct information and identification of the product. Tamper evident / Child resistance/ Anti counterfeiting.

Functions of Packaging: Containment y Not to leak, nor allow diffusion and permeation y Strong enough to hold the contents during handling  Protection y Light y y Moisture y y Oxygen y

Biological contamination Mechanical damage Counterfeiting

Criteria for the Selection of package type and package material:               
Stability Compatibility with the contents Strength of container and the degree of protection required Moisture-proofness Resistance to corrosion by Acids or Alkalis Resistance to grease Protection against salt Resistance to microorganisms Resistance to insects and rodents Resistance to differences in temperature Protection against light, fire and pilferage Odor retention and transmission Aesthetic effect Cost Machine suitability of packaging and the filling method Convenience of the packaging for the physician, pharmacist and finally the patient (size, weight, method of opening/re-closing, legibility of printing)
M.PHARM SEM-II (2009-10) L.M.COLLEGE OF PHARMACY, AHMEDABAD ² 09

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AHMEDABAD ² 09 4 . Choosing appropriate primary pack  Product characteristics\sensitivity y Hygroscopicity y Physical degradation y Chemical degradation y Drug release properties  Selection of packaging material y Moisture barrier requirements y Light barrier requirements y Mechanical properties y Photosensitivity y Gas liberation tendency y Dimensional aspects y y Gas barrier requirements Chemical properties Secondary packaging material used external to the primary pack which provides physical protection to ensure safe warehousing and mechanical protection required in shipment and transport.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Types of Packaging: Packaging may be two types: Transport package or distribution package is the package form used to ship. packaging may be three types: y Primary packaging y Secondary packaging y Tertiary packaging Primary Packaging  Primary packaging material is the material that first envelops the product and holds it. leaching.PHARM SEM-II (2009-10) L. store and handle the product or inner packages.  Material characteristics y Primary Packaging material should not have adverse effect on product due to chemical reaction. freezing). y It must not alter the identity of the product. y It should not be affected by product. particulate contamination. y It must preserve the characteristics properties of the product to comply specifications.It has functions: y Protection from excessive y Transmission of reactive gases y Moisture y Light y Microbes y Protection to flexible container y Protection from rough handling during transportation M. biological or physical entities. y It must protect product against undesirable or adulterating chemical. y It must preserve the physical properties of all dosage forms and protect them against damage or breakage. that is those package components and subcomponents that actually come in to contact with the product or those that may have a direct effect on the product s helf life. y It should not be influ enced by adverse manufacturing condition (sterilization.COLLEGE OF PHARMACY. According to the packaging material.M. absorption or adsorption.  Consumer package is directed towards a consumer or household.

PAPER-III NDDS (PART-I) Pharmaceutical Packaging Tertiary packaging is used for bulk handling and shipping.  Resin identification code consist of arrow that cycle clockwise to form rounded triangle and enclosing a number where as the number inside the recycling symbol indicates about the number of recycling process applied on plastic material. It provides primary defense against external hazards and have shock absorbing features. AHMEDABAD ² 09 5 . The cartons are made up of cardboard. and Recycling direction are common to allow automated information management.PHARM SEM-II (2009-10) L. molded woo d pulp and expanded polystyrene.  Carton\outer: It is the outer covering. moisture and microbes and prevents the loss of water and other volati le substances form the product. They are made up of thick cardboard and wood. carbon dioxide.  Box: In the box.  Closure: It tightly packs the container to exclude oxygen. RFID labels. ampoules Pre-filled syringes Aerosol containers Pre-filled inhalers Paperboard containers Wrappers Secondary Cartons Prescription dispensing containers Corrugated boxes Paper drums Shipping containers Injection trays Tertiary Barrel Container Intermediate bulk container Slip sheet Crate Edge protector Pallets Stretch wrap Components of Packaging: Container: It refers in which the product or medicine is placed and enclosed. M.  Bar codes. Primary Glass bottles. Universal Product Code.  Some requirements symbols exist to communicate aspects of consumer use and safety.M. jars Plastic bottles Strip packs Blister packs Pouches Ointment tubes Vials. multiples of the products are packed. Resin identification code .COLLEGE OF PHARMACY. It remains in direct contact with the drug. Symbols used on Package and Labels: Many types of symbols for package labeling are nationally and internationally standardized. which gives secondary protection against mechanical and other environmental hazards and also serves for display of written information.

cans. foil. stems. filling. retailer. lids. aerosol containers. The type of patient: child. syringes. Capacity of packaging needed. needles. vials. AHMEDABAD ² 09 6 . M. pharma cy. vial wrappers.PHARM SEM-II (2009-10) L. aerosol containers. taps. PACKAGING MATERIAL:Packaging material must have following properties:  Mechanical properties y Container should be strong enough to withstand the shock during handling. foils. ointment. The degree of the protection required. ampoules. vapors and microbes. caps.PAPER-III NDDS (PART-I) Pharmaceutical Packaging TYPES OF PACKAGING MATERIALS:Type of Materials Glass Plastic Rubbers Paper\cardboards Metals Use Bottles. syringes. closing. taste and odor to the preparation.  The choice of the packaging material will depend upon: y y y y y y y The dosage form desired. gases.g. Closure must be easy to remove and replace. paper drums. Container and closure should not react with each other and preparation. Method of distribution: hospital.  Physico-chemical properties y y y y y y The container should not absorb substances from the product. Labels. Closures. laminates. tubes.COLLEGE OF PHARMACY. Presentation and aesthetics Customer convenience e. It should protect light sensitive drug.  The choice of the packaging for a specific product is dependent upon: y y y y y y y The nature of product and its compatibility with material. pouches. size. It should be non -reactive with the contents of preparation. elderly. boxes. weight of dosage form. storage and transport. pouches. Method and the site of administration. Filling method Sterilization method to be employed and cost. plungers. aerosol containers. The type of dose: granules. y It should be impermeable to avoid any loss of product or contamination by liquid. laminates. Required shelf life and likely sales area. Collapsible tubes. Bottles. adult. Compatibility with dosage form. display units. y It can withstand heat during sterilization. It should not impart its own color. inserts. bags. cartons.M. tablet. gum tapes.

y The presence of many additives may bring about the drug-plastic interaction y Alteration in physical properties of the product. parenteral.  Advantage y It has very good mechanical strength.  Disadvantage y Plastic are permeable to vapor. y The stability of the product towards: light. external.A. capa ble of being molded in to variety of shapes and forms by utilizing heat or pressure. dispose.  This can be used as homo or co-polymer or in combination with aluminum and board. moisture.COLLEGE OF PHARMACY. y Range of the plastic material available. close. pilfer-proof. y It should not affect the therapeutic value of the product. light. y It should have suitable life. PRIMARY PACKAGING MATERIALS:PLASTIC  A plastic packaging material is supposed to be strong. easy to carry. convenient to open.PHARM SEM-II (2009-10) L. and tamper evident. y They reduce the cost due to their less weight. carbon dioxide and trace metals. y Emulsifier y Modifiers y Acceleration y Stabilizers y Flame retardants y Anti static agents y Mould release agents y Extenders y Antiblocking agent y UV absorbers y Catalyst y lubricants y fillers y Antioxidants y Opacifiers y Colorant y light excluders y Plasticizers y Antislip additives M. y The cost of the container should be proportionate with the cost of the product. liquid or gas. y Plastic are poor conductor of heat.  Additives are present in plastic containers.  Pharmaceutical properties y Dosage form of the product: solid.  It is consists of polymers of high melting point. y The route of administration of preparation: oral. protective. which should be comparable with the stability period of the product.  Economical aspect y Cost wise the container and closure should be reasonable.M.  Biological properties y The container should not produce any toxic effect. y The majority of the plastics are sensitive to heat & cause leaching. y They are non breakable. y Plastic containers are obtainable in multipurpose design. approved. which may satisfy requirement of the pharmaceutical packaging. AHMEDABAD ² 09 7 . y It should be able to withstand attack by insect and should not support mould growth. aesthetic.PAPER-III NDDS (PART-I) Pharmaceutical Packaging y The materials used in the container should be F.D. oxygen. use or administer. semisolid.

M. -More permeable to water vapors. -Bottles -Jars closures -Packaging films and laminates 6.P.Polyolefin( low density polyethylene) Properties -Flexible. Similar to H. tubes for topical ointment. jars.D. food and cosmetics. -Hard rigid -Light material -Easy to mould -Permeable to water vapors -Not sterilizable -Excellent heat resistance -Impermeable to water vapors. personal product. vapors. -High resistant to oils.T.F. Poly propylene 4.) 5. -lack of transparency -Non-adherence of labels -Charged with static electricity. but lighter. milk. inert. foods. bottles. tough -Impermeable to water.E. vapors. -Disposable syringes -For dialysis fluids -Drugs & cosmetics -Syrup.P.COLLEGE OF PHARMACY.) M. 3. and suppositories pack. AHMEDABAD ² 09 8 . y Crystalline plastics have low permeability to gases and moisture and are more inert. low cost.PAPER-III NDDS (PART-I) Pharmaceutical Packaging  Plastic may be two types: y Amorphous plastics are more permeable to gases and moisture but are less inert. -High clarity.) -Disposable syringes -Packaging of pharmaceutical preparation. 2.V. impermeable to water vapors. flexible acquired original shape. Polyvinylidene chloride(P. Polystyrene -Spoon -Bottles -Jars closures -Not suitable for sterile product. closures. -Expensive -Difficult to fabricate -Resistance to solvents and chemicals. -High permeability to gases. very light. translucent and inert.D.PHARM SEM-II (2009-10) L. -Permeable to oil preservatives. and hardness with possible brittleness..C. bottles. infusion fluid. High density polyethylene (H. -Less permeable to gases than polyethylene. -More rigid. detergents. less opaque. -Impermeable to water.Polytetrafluoroethylene (P. -Less flexible than polyethylene. transparency. squeeze bottle -For retention enemas -Bottle jars -Suppositories -For retention enemas. Application Cosmetics. more heat resistant. They are opaque or translucent and more flexible. -Sterilized by autoclaving. Types of Plastic 1. juices. They offer good clarity. -Easy handling and filling container.

bottles. recyclable. sterilizable. Cullet is broken glass that is mixed with the batch. syringes and cartridges. -Not for alkali sensitive materials. It provides good light protection. Types Properties Application Type I Highly resistant. -Not generally used for parenteral preparation until and unless indicated.M. ovenware. resistant to high temperature. y Glass posses FDA approval. AHMEDABAD ² 09 9 . -For blood plasma. -For alkali sensitive materials. y It is non-corrosive. chemical inert. Polyamides(Nylon) 8. y It is transparent and sparkles. -Preparation of Parenteral administration. Where sand represents for pure silica. y It has high cost due to the high weight. lime-stone and cullet.COLLEGE OF PHARMACY. M.  Advantages y Glass as a packaging material is chemically inert. Polycarbonate -Very tough -non transparent -highly permeable to water vapors -heat resistance -Transparent -Stable -Heat resistant -Packaging films and laminates -Packaging films and laminates GLASS  Glass is composed of sand.PAPER-III NDDS (PART-I) Pharmaceutical Packaging 7. which acts as fusion agent for entire mixture. vials. -Chemical. -Only for non-aqueous products.  Disadvantage y Glass is fragile. hygienic. It is an alkaline glass having a high percentage of lime and soda and no boric oxide as compare to the type I glass. y It is impermeable to water vapors. -Preparation for Parenteral administration. soda ash. glassware. borosilicate glass Type II Treated sodalime glass Type III Soda-lime glass Alkalinity is removed by using boric oxide to neutralize the oxides of potassium and sodium. impermeable with no diffusion or leakage.PHARM SEM-II (2009-10) L. soda ash for sodium carbonate and lime-stone for calcium carbonate. Obtained by treating the hot surface of the type III glass by sulfur dioxide/ammonium sulfate/ammonium chloride. y It does not undergo any change on aging. y It imparts no odor and taste to the product. y It is strong and rigid. strong and rigid.  It is economical. -For alkali sensitive materials. easily washable. y It offers less pressure safety and impact resistance. compatible and transparent.  A number of glass containers in pharmaceutical industry incl ude ampoules.

g.g. -Do not use for parenteral unless specified. As lead monoxide is used in manufacturing of glass cause lead poisoning. y Ampoules are made up of neutral glass. -Used for liquid preparation. y There are several types of absorption: -Electron transfer between cations and anions. minerals like copper for red. absorption can occur in either the visible or non -visible spectrum. -In addition to glass composition. blue or green.D. Non parenteral article as oral or topical use. y Depending on the ions used. y For e. disposable syringes and aerosol.A. Fe absorb around 1000 -1100 nm and gives the glass a blue tint.COLLEGE OF PHARMACY. y Vials are produced by soda glass when used for tablets and capsules. tin for yellow are added. Cu can be formed by heat treatment and gives silver-yellow or golden-red color. yellow brown. blue green. Electrical properties  Volume resistivity 3. Lead free glass Silicon treated -Surface is treated with dimethyl siloxane. -Used for light sensitive material product. cartridge tubes. There were one first unit dose containers but are being replaced by cartridge tubes and pre-filled syringes. Glass properties 1. Na E.  Application y Glass is used for different containers ranging from ampoules. y The color of the transparent material like glass is due to the absorption of light at certain wavelengths in visible spectrum.  Colored glass y In colored glass. Injection vials can be obtained in neutral or soda glass of occasionally in treated soda glass. It also includes pale blue.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Type NP General purpose soda-lime glass Colored glass It has similar composition to that of the type III glass but has no similar properties. iron for black. Chemical properties  Sodium/alkali leaching 2. carbon and sulfur or iron and manganese for Amber color. -Does not allow the UV rays to pass through it.PHARM SEM-II (2009-10) L. red and black. amber.. olive green. vials. Mechanical properties  Stress 4. Optical properties  Refractive index  Dispersion  Alkali/Acid resistance  Surface resistivity  Density  Absorption  Transmission  Dielectric constant  Specific gravity  Reflectivity  Birefringence constant M. dark blue. -As hydrophobic nature not welled so product do not cling to surface. -Used when preparation meant for lead poisoning e.T. -Used for liquid preparation.M. metal salts. AHMEDABAD ² 09 10 .

highly crystalline. y It offers excellent barrier properties to the moisture.  Aluminium y It is the most abundant of the all metals. the foil is extremely pliable.  Aluminium foil y It is the aluminium prepared in thin sheets. y It is good thermal and electrical conductor and is capable of being superc onductor. vomiting and other symptoms of poisoning are occur.PAPER-III NDDS (PART-I) Pharmaceutical Packaging 5. The strongest aluminium alloy has less corrosion resistance due to galvanic reactions with alloyed copper. They are resistant to high and low temperature. ductile. y It has excellent corrosion resistance due to the thin surface layer of aluminium oxide that forms when the metal is exposed to the air. as a result of this. The chief source of it is bauxite ore. glass odor and bacteria. Thermal properties  Coefficient of thermal expansion (CTE)  Thermal conductivity  Specific heat  Thermal shock  Softening point METALS  Metal containers are strong.PHARM SEM-II (2009-10) L. y It combines directly with chlorine and oxygen and displaces hydrogen from dilute acids.g. and can be bent or wrapped around objects with ease. AHMEDABAD ² 09 11 . Some of these closures are similar to those used on the glass and plastic container e. y Aluminium foil laminated with paper or plastic is used as heat sealed membrane hermetically closing the container under the plastic screw cap and provides excellent barrier properties preventing moisture or gas transmission and tamper evident seal. It resists corrosion from distilled. seal and soft tap water. y Allergic reaction. alkalis. y It is mainly suitable for blister packs and strip packs. y It is sometimes known as al-foil or alu-foil and tin-foil. unbreakable. preventing the further oxidation. y It is most widely used for packaging of tablets and capsules.  Due to their chemical reactivity.COLLEGE OF PHARMACY. Reynolds wrap. but can be attacked by strong acids.  Tin y Tin is malleable. opaque and impervious to water vapor. y Tin can be highly polished and is used as protective coat for other metals in order to prevent corrosion or chemical action. M. cosmetics and chemical products. and by acid salts.  Metals are also used for the formation of closures. gas and light. silver paper. silvery white metal.  Precaution: y Aluminium is neurotoxin that alters the function of the blood -brain barrier and cause the Alzheimer s disease.M. y Millions of the aluminium foil are u sed for protection and packaging of food. plastic & m etal screw closures and friction closures such as plug /slip lids. y It gives slight tin taste to food wrapped in it. metals require the application of coating and lacquers to prevent the chemical reaction and corrosion.

These form thin films using minimum material are cost effective. y Wax linings are most often used with water based products in tin tubes. y This true metal is highly resistant to corrosion. y Cost of lamination process and the yield. y Lead has lowest cost of all the tubes metal and is widely used for the product as fluoride toothpaste. ductile. very soft. bluish white metal that has poor electrical conductivity. y It can be toughened by adding a small amount of antimo ny or other metals to it. It changes the optical characteristics of the glass and reduces the transmission of radiation. but the most common ones in use are tin. depending upon: y Availability of the material. and phenolics. it is used to contain corrosive liquid (sulfuric acid). y Cost of base material. y The main pharmaceutical application of lamination include. cellulose. which is now referred to as tin foil. etc. y It is very poisonous. include paper/foil/polythene and paper/foil/surlyn.M. y Tin foil was once common wrapping material for foods and drugs. highl y malleable. giving the better protection against alkaline materials than wax. M. replaced in early 20 th century by the use of aluminium foil. aluminium and lead. epoxides.  Lead y It has dull luster and is dense. y Technical requirements. y Any laminate may consist of number of plies selected from paper.  Laminates y Laminates are combination of different plies put together to get some desired properties. y Two laminations are widely used. y Aluminium tubes offer significant saving in product shipping costs because of their light weight and provide attractiveness of tin at lower cost. y Small tubes are often made of tin even though the metal cost is higher. with good reclosure. Due to these properties. ‡ Any ductile metal can be worked cold as suitable for collap sible tubes.PAPER-III NDDS (PART-I) Pharmaceutical Packaging y It is malleable at ordinary temperature but brittle when it is heated. Laminates of tin coated lead provides appearance and oxidation resistance at lower prices. The risk of the contamination of the portion remaining in the tube is minimal because the tube is not suck back . and vinyls are used with aluminium tubes. film foils coating. and adequate protection of the product. blister.  Collapsible metal tube y The collapsible metal tube is an attractive container that permits controlled amount to be dispensed easily.PHARM SEM-II (2009-10) L. but at higher cost.COLLEGE OF PHARMACY. AHMEDABAD ² 09 12 . str ip and sachet packaging are mainly child resistant packaging.

 These caps are usually made of aluminium and may be equipped with plastic top to facilitate opening. There are mainly four types of the rubber:  Butyl rubber (co-polymers of isobutylene and isoprene or butadiene). tin free steel. aluminium alloys.PHARM SEM-II (2009-10) L. with desired aging properties and low water vapor permeability. whereas atmospheric pressure is utilized in vacuum-sealed tin. adhesives. etc.  Neoprene rubbers are resistant to oil and heat with low water absorption and permeability as compared to natural rubbers. tin plate.  The materials employed for the formation of closures include. welding. namely altering. polyethylene. These are made from aluminium foil.  Butyl rubbers are cheap. These forms tamper evident pack. heat seals or electrical heat sealing. heat treatment. pilfering and falsifying the pharmaceutical product.  Pressure type closures make the use of mechanical and atmospheric pressure. y Nitrile rubbers (butadiene -acrylonitrile co-polymers). chemical resistant. y Liners are generally used in the inner side of the containers. strength and aging properties. vapor absorption and permeability but leaching and bactericide absorption is high. It is not good for oils. by some source of contamination and impurity.  Though the primary function of closure system is to contain contents.PAPER-III NDDS (PART-I) Pharmaceutical Packaging CLOSURES  A closure forms the most critical component of the container. tin foil.g.  Mainly closures are made from elastomers (rubber). y Materials like aluminium.  Caps and over seals are used to secure the rubber closure to the container in order to maintain the integrity of the seal under normal condition of handling and storage.  Use of temperature is made in case of closures e. y Chloroprene rubbers (Neoprene. temperature and adhesion. AHMEDABAD ² 09 13 . loss of quality.COLLEGE OF PHARMACY. seepage. cold seal material etc. polymers of 1:4 chloroprenes). pilferage.  Silicon rubbers are costly but most heat resistant with very low water absorption and permeability. stainless steel. as far as the stability and compatibility are concerned. M.M. y Glass is used for formation of stoppers. PVDC coating etc. SPECIFIC TYPES OF CLOSURES: Tamper-evident closures y Tampering include three aspects. y Silicon rubbers. Mechanical pressure is utilized in screw closures. plug seal. y Rubbers and plastics (may be thermosetting or thermoplastic type).  Nitrile rubbers are resistant to oil. safety and security may be necessary to prevent hazards resulting in leakage.  Adhesion is made use of in the closures in t he form of solvents. y Tamper evident closures are designed to prevent the accidents and malicious tampering to create safe packaging. lever lid.  Closures may be achieved by a number of basic means or combination of it s including pressure. purity etc.

‡ Chemical Pulping uses chemical solutions to convert wood into pulp. yielding around 30% less than mechanical pulping.COLLEGE OF PHARMACY. lay term used to refer to any heavy paper pulp based board. y International standards have been laid down by ISO and ECN (European committee for standardization for child resistant closures).M. while being easier for the adults to open. y bleaching methods: y Bleaching by delignification using chlorine gas. oral cosmetic liquids. which is a generic. because of the presence of lignin.  Pulping  Mainly two methods for extracting fibres from its source are used: ‡ Mechanical Pulping is a two stage process which results in a very high yield of wood fibres.PHARM SEM-II (2009-10) L. Sometimes it is referred to as cardboard. is lightweight. and is strong used in packaging. non-specific.  Bleaching y Pulp used in the manufacture of paperboard can be b leached to decrease colour and increase purity. y These have proved effective in reducing child mortality from intoxication by oral prescription drugs. y Various types of tamper evident packaging include: y Film wrappers -Breakable cap ring systems y Blister packs -Sealed tubes y Bubble packs -Plastic bind end sealed tubes y Heat shrunk bands or wrappers -Sealed cartons y Plastic foil for plastic packs -Aerosol containers y Bottle with inner mouth seals -Metal and composite cans y Tape seals  Child resistant closures y Tragic accidents involving the drug intoxication of children has led to new legislation making it difficult for drug packaging to be opened by young children. Paperboards used for the manufacture of corrugated fiberboard are called containerboard. These are termed as child resistant closures. Paperboard used for the manufacture of folding cartons and rigid set-up boxes is often called boxboard.  Production  Fibrous material is turned into pulp and bleached to create one or more layers of board. contact lens solution and tablets. Recycled paperboard may contain traces of inks. AHMEDABAD ² 09 14 . which can be optionally coated for a better surface and/or improved visual appearance. M.PAPER-III NDDS (PART-I) Pharmaceutical Packaging y These are used for products ranging from OTC drugs. Virgin fibre pulp is naturally brown in colour. y The three most common child resistant closures are press -turn. SECONDARY PACKAGING MATERIALS:PAPERBOARD  Paperboard can be single or multi-ply. squeeze-turn and combination lock. toothpaste and topical and dermatological products. bonding agents and other residue which causes a grey coloration. It can be easily cut and formed.

!   C " UGA D FIBERBOARD  Corru ated fiberboard is a paper-based material consisting of a fluted corrugated sheet and one or two flat linerboards. etc). doublewall. Alternatively.  Corrugated fiberboard can be specified by the construction (single face. slots are cut to provide flaps on the box. or 0. one or more layers of coating is applied. although cardboard might be any heavy paper-pulp based board.25 mm) thick. flute size. It is widely used in the manufacture of corrugated boxes and shipping containers. Coatings are made up of: a pigment like china clay. surface treatments and coatings. Classifi ations ‡ FBB/GC/UC (Foldin Box Board) which gives it a light yellow colour. paper-like material usually over ten mils (0. singlewall. sheets of corrugated board may be sent to a different manufacturing facility for box fabrication.COLLEGE OF PHARMACY. burst strength. ‡ WLC (White Lined Chipboard) is a board made from virgin and recycled material (grey). AHMEDABAD ² 09 ¦¥ ¦ ' & % % 15 £ ¤ £ PAPER-III NDDS (PART-I) Pha aceu ca Packag ng ¢ #  ¡    # $ ¨ ¨ $ § © ¨ ©     ©¨ § .y Ble c by oxidation us c e c ls suc as c lorine dioxide hydrogen peroxide or sodium hypochlorite y Bleaching by redu tion using chemicals such as sodium bisulphite  Coatin In order to improve whiteness smoothness and gloss of paperboard. etc. flat crush. BOX  Boxes can be formed in the same plant as the corrugators. calcium carbonate or titanium dioxide.  Box co pression test The box co pression test measures the compressive strength of boxes made of corrugated fiberboard as well as wooden boxes and crates. Most often.  Double and triple-wall corrugated board is also produced for high stacking strength an d puncture resistance. The corrugated board is creased or scored to provide controlled bending of the board. ‡ SBB/SBS/SUS (Solid Bleached Board) which is white throughout. adhesive or binder & water. Paperboard and corrugated fiberboard are sometimes calledca dboa d. edge crush strength. OBA (optical brightening agents . The BCT value is a measure of the strength of a shipping container and is measured in N ilonewton or pounds of force: deflection or deformation is measured in mm or inches. grams per s uare meter. etc). Scoring and slotting can also be accomplished by die cutting. ‡ SUB (Solid Unbleached Board) is a board made from unbleached chemical pulp (yellow) or recycled material (grey). It provides a plot of deformation vs compressive force.010 inch. PHARM SEM-II (2009-10) L M. basis weights of components (pounds per thousand s uare feet.

y Stored in Adequate thickness bags.  Blister packs are commonly used as unit-dose packaging for pharmaceutical tablets. y Temperate climate: 72 hrs in winter 48 hrs in summer  Tropical climate: 48 hrs during winter 24 hrs during summer PACKAGING OF SOLID DOSAGE FORM (Unit-Dose Packaging): Blister pack is a term for several types of pre-formed plastic packaging used for small consumer goods. y Absorbent material in sufficient quantity to absorb the entire contents placed between the primary receptacle and the secondary packaging. The two primary components of a blister pack are the cavity or pocket made from a "formable" web. plastic or aluminium. stretch wrap. crate container. or a metal crimp seal). y Placed in bins with vent. carton. The "formed" cavity or pocket contains the product and the "lidding" seals the product in the package.  Folding cartons are usually combined into a tube at the manufacturer and shipped flat (knocked down) to the packager. Many cartons are made out of a single piece of paperboard.  Materials Cartons can be made from many materials: paperboard.  It mainly helps in bulk transportation. and a degree of tamper resistance. intermediate bulk container.  Storage ‡ No Storage of untreated BMW > 48 Hrs g y Waste stored in bags must be properly tied. either plastic or aluminium . Sometimes a carton is also called a box. bulk bags . capsules or lozenges. various plastics. slip -sheet. y Use NaOCl & Formalin applicable and required. big bag. or super sacks . a heat seal.COLLEGE OF PHARMACY.. This may serve to contain a liquid product or keep a powder dry.g. or a composite. PACKAGING REQUIREMENTS FOR INFECTIOUS SUBSTANCES: Packaging should include the following essential elements: y An inner packaging comprising: y Watertight primary receptacle of metal or plastics with leak-proof seal (e. made from paper. Many types of cartons are used in packaging. Blister packs can provide barrier protection for shelf life requirements.PHARM SEM-II (2009-10) L. Tray styles have a solid bottom and are often shi pped as flat blanks and assembled by the packager. M. It includes barrel.PAPER-III NDDS (PART-I) Pharmaceutical Packaging CARTON  Carton is the name of certain types of containers typically made from paperboard which is also sometimes known as "cardboard .and the lidding.M. Depending on the need. pallets. AHMEDABAD ² 09 16 . this paperboard can be waxed or coated with polyethylene to form a moisture barrier. skirted stopper. edge protector. TERTIARY PACKAGING MATERIALS: Tertiary packaging materials is used for bulk handling and shipping.

is considered airtight. or glycol-modified polyethylene terephthalate (PETg).(also known as Band type heat sealers) utilize heated moving belts. thermostats.  COC y Cyclic olefin copolymers (COC) or polymers (COP) can provide moisture barrier to blister packs. PVC blisters offer structural rigidity and physical protection for the pharmaceutical dosage form. The food. y Paper/PET/aluminium laminate is used for child resistant push -through packages.  Applications y Applications for hermetic sealing include semiconductor electronics. Electronic parts that are designed and intended to secure against the entry of microorganisms and other foreign bodies to maintain the proper functioning and reliability of their contents. and switches. Ultrasonic welding uses high-frequency ultrasonic acoustic vibrations to workpieces being held together under pressure to create a weld.  The main advantages of unit-dose blister packs over other methods of packing pharmaceutical products are the assurance of product/packaging integrity (including shelf life) of each individual dose and the possibility to create a compliance pack. In the case o f blister packaging the PVC sheet does not contain any plasticizer and is sometimes referred to as Rigid PVC or RPVC. Materials . Heat sealer  A heat sealer is a machine used to seal products packaging.PHARM SEM-II (2009-10) L.use a stationary element which is heated with each sealing cycle .  PCTFE y Polychlorotrifluoro ethylene or PCTFE can be laminated to PVC to obtain very high moisture barrier. temperature and pressure for the correct clean material. In some parts of the world the blister pack is known as a Push-Through-Pack (PTP). and pharmaceutical industries all have M.COLLEGE OF PHARMACY. chemical. and thermoplastic materials using heat.Pharmaceutical blister packs  PVC y The most basic material for the forming web is PVC or Polyvinyl Chloride. AHMEDABAD ² 09 17 . Cyclic olefin resins are generally amorphous and are noted for good thermoforming characteristics. Good seals are a result of time. Hot bar sealers.use one (or two) heated bars which contact the material to form a bond.M. for practical purposes. optical devices.PAPER-III NDDS (PART-I) Pharmaceutical Packaging  A series of blister cavities is sometimes called a blister card or blister strip as well as blister pack.  Hermetic seal A hermetic seal is a seal which. typically in multilayered combinations with polypropyl ene (PP). The main disadvantages are the poor barrier against moisture ingress and oxygen ingress. In the absence of plasticizers.        Types of heat sealers Continuous heat sealers. Impulse heat sealers. Induction sealing is a non-contact type of sealing used for inne r seals in bottle caps. polyethylene (PE). The principal advantages of PVC are the low cost and the ease of thermoforming.

M. plastic.  Plastic bottles are used for Nasal & Ophthalmic packing. Tin cans are hermetically sealed.  Other lamination suitable for strip packaging is paper/polyethylene/foil/polyethylene. which are tamper resistant. use an inner seal that bounded to the neck of the bottle. foil or combination of these.  ‡ ‡ ‡ ‡ ‡ Factors affecting blister thickness: The nature of the material Softening temperature Hardening time Process Thickness of film.  Usually cellophane film which has heat sealable nature and transparency is used. especially when the visibility of the product is important. activity. enables this packaging suitable for moisture-sensitive products. AHMEDABAD ² 09 18 1 2 1 )( PAPER-III NDDS (PART-I) Pha aceu ca Packag ng 0 3 .COLLEGE OF PHARMACY. and high barrier plastics (with effective heat seals).  Pressure sensitive inner seal and heat sensitive adhesives can also be used for the purpose of the tamper proof bottle packaging for which mainly aluminium foil is used for sealing. and shelf-life dictate high standards for injectable drug packaging particularly for highly active peptides and proteins. Strips packaging  This pack consists of one or two plies. made from regenerated cellulose. metals.applications for the use of such "airti ht" packaging.  Fluoroelastomer coating on stoppers provide the barrier protection and safety from leaching. 4  TYPES OF PAC AGES:y Vials and bottles y Ampoules y Prefilled syringes 5 BOTTLES & JARS  Bottles are the containers in which the multiple dose parenteral preparation is packed. paper. AC AGING OF AREN ERAL LIQUIDS: Re uirements for product purity. such as glass. light and chemical contaminants. The material of these containers is glass & plastic.  The use of high barrier material like foil or saran-coated film with excellent seal formation .  Lyophilized proteins are sensitive to heat.  Glass seal.PHARM SEM-II (2009-10) L.M. Product is sealed between the two sheets along with a seal around each tablet/capsule and perforation of easy cutting.

y Sizes are available from 2 ml up to 100 ml.  Material for it is glass with rubber cap. y OptiVial TM with its uniquely shaped bottom to eliminate leftover substances y Dual-chamber vials y Screw neck vials y Tablet vials. Integrated printing avoids contamination. The vials are provided with the closure followed by aluminium seal to ensure the perfect air tight packing. as well as assembled with caps and droppers.  Vials made of polymer y Vials made of advanced cyclic olefin copolymer (COC) of highest purity offer transparency comparable to glass.M. They can be administered in the form of pen or pump systems.COLLEGE OF PHARMACY. They can be ordered pre-washed and siliconized.PHARM SEM-II (2009-10) L. A wide variety of ampoule types from 0. Sophisticated delivery systems require a rigorous level of precision and quality for all dimensional and functional aspects. high chemical resistance and breakage resistance make these vials ideal primary packaging for many different applications. The break systems OPC (one-point cut) or the color break ring offer consistent breaking force. Mainly diagnostic agents and vaccines are packed in this pack. The filled-in product is in contact with glass only and the packaging is 100% tamper proof.5 to 50 ml.  Different vials y Perfume sample vials. Up to 3 color rings can be placed on the stem or body for identification purposes. Material for it is mainly glass. CARTRIDGES  Cartridges are used in large volumes and are an ideal packaging method for insulin and other drugs. y Special designs for lyophilization. ‡ Cartridges for pen systems ‡ Cartridges for pump systems ‡ Dual-chambered cartridges for dual-component application ‡ Cartridges for auto-injectors ‡ Cartridges for needle free injectors ‡ Dental cartridges PREFILLABLE POLYMER SYRINGES  This type of packaging system is employed on small dose parenteral preparation.  Dropper pipettes in a wide range of shapes and colors are available. y Excellent barrier properties.PAPER-III NDDS (PART-I) Pharmaceutical Packaging VIALS  Vials made of glass y Vials are mainly used for multiple parenteral preparation. The material for syringes is glass and plastic. AHMEDABAD ² 09 19 . M. and the special packaging is ready for the sterilization process. AMPOULES  Ampoules are a great primary packaging for a variety of drugs. Printed ampoules with heavy metal free colors are available.

resists puncture. PACKAGING OF MEDICAL / SURGICAL DEVICES:The medical device packages are usually evaluated to meet the following requirements: y They must be capable of being sterilized economically.M.  Pull sealing is slow but it prevents combustion products of flame from entering the ampoule at the time of sealing. Recently plastic ampoules for water for injection are available in the market. y They must withstand the shipping and handling environment. etc.PHARM SEM-II (2009-10) L. chemicals.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Generally ampoules are made up from the glass. y They must be compatible with the procedures set up by the ho spitals. y Sterility y Environmental y Product resistance: oils. water. tearing. provides cushioning and structural support. gas. The types of tests carried out for Medical Device Packages are as follows: y y y Sterility Testing Manual handling Vehicle stacking y y y Loose-load vibration Vehicle vibration Drop test M. y Physical: Dimensional stability (rigidity or flexibility. abrasion. AHMEDABAD ² 09 20 . Evaluation of Medical Device Packages: The Medical Device Packages Testing Laboratory is set up with the following principle goals: y To evaluate the component materials of container and the inner protective cushioning materials y To develop (through research) improved methods or concepts and improved package testing techniques. then pulling the tip away to form small. impact and pressure.COLLEGE OF PHARMACY. twisted capillary prior to being melted closed.  Tip seal is made by melting sufficient glass at the tip of the ampoule neck to form bead of the glass and close the opening. as occur with tip sealing. Two types of the seal like tip seal and pull seal.  Pull seals are made by heating the neck of rotating ampoule below the tip.      Type B straight-stem Type C funnel-tip Type D closed Double tip (1 25 ml) Fine tip (1 25 ml) Sealing  Tamperproof sealing of the ampoule is essential.

y If three or two deliveries are outside the limits. spray or stream.Two piece-welded side seam or drawn (b) Aluminium 1. It should be inert with the ingredients of the product. if four or more are outside the limits.sprays. The lot is accepted if not more than one delivery is outside the specifications. y Tip-sealing valves y Metering valves y Vapor tap valves y Foam valves y Powder valves y Compressed gas valves  Actuators: The actuator is the molded part on the top of the valve stems that determining whether the product will be dispensed as a f oam. antioxidants and surfactants. Testing of Aerosols packaging containers  Valve acceptance: The test procedure of metered valve having the following value: 54µL or less.PAPER-III NDDS (PART-I) Pharmaceutical Packaging y Compression y Package seal strength testing PACKAGING OF AEROSOL  Types of the materials for Aerosol containers: (a)Tin plated steel 1. M.  Types of valves: y Spray-any-way valves.  Product concentrate: They include solvents.Two piece-Extruded drawing  Valve: The valve in the aerosol facilities the dispending of the product. AHMEDABAD ² 09 21 .Drawn and ironed 2. Different types of valves dispensed the product as.COLLEGE OF PHARMACY.Three piece-soldered side seam 2. They are used for the inhalers.  Spray nozzle: It is metered to allow a specific dose to be dispensed with each spray.M. the valves are rejected .PHARM SEM-II (2009-10) L.One piece-Extruded (c) Stainless steel (d) Glass uncoated (e) Plastic coated glasses (f) Plastic and synthetic resin  The parts of the containers packaging: 3. solid streams and foams. the limits are 15% 55 to 200µL. another 25 valves are sampled and test is repeated. the limits are 10% y Of the 50 individual deliveries. y Different types of actuators: y Solid stream actuator y Spray actuator y Foam actuator y Metered-dose inhalers  Dip tube: They are made from polyethylene.

AHMEDABAD ² 09 E D 22 9 @ 9 76 PAPER-III NDDS (PART-I) Pha aceu ca Packag ng 8 C . Titrate with 0.7 8.  Spra testing: This method is based on the impingement of the spray on the paper that has been treated with a dye-talc mixture. Weight checking: This is usually accomplished by periodically adding to the empty aerosol containers. autoclave for 60 mins. This gives the record of spray. Add the 5 drops of methyl red solution.PHARM SEM-II (2009-10) L. The particles that strike the paper cause dye to go into solution and to be absorbed onto the paper. which after being filled with concentrate. Cool the flask in running water. Add 5 drops of methyl red solution as an indicator. mpty the contents and pool the contents in 250 ml conical flask to a volume of 100ml. Titrate immediately with 0. Cap all the flasks.02 N sulfuric acid. Decant the water. Fill each container to 90 of its overflow capacity.5 15. Record the volume of 0.02 N sulfuric acid while warm (complete titration within 60 mins). are removed and accurately weighed to check the accuracy of filling operation. B Type of the glass I II III IV Types of the test Powdered glass test Water attack test Powdered glass test Powdered glass test Li its si e(ml) All 100 or less All All Limits(ml of o.COLLEGE OF PHARMACY. Wash the residual powdered glass (4 times with 15 ml high purity water). Periodic checks are made of the temperature of the water bath and the results are recorded. Add the decanted washing to main portion.02 N sulfuric acid.0 0.M.o2N) 1.  Leak testing: The testing of efficiency of the valve closure is accomplished by passing the filled containers through the water bath.0 Water attack test at 121 c (USP) Rinse 3 or more containers twice with high purity water. M. A Volume doesn t exceed that indicated in table for the type of glass concerned.

 Light transmission test y A spectrometer is suitable sensitivity is used to cut the section of glass container. The transmittance of the selection is measured and observed light transmission is not expected to exceed the limits provided in the table. No sign of leakage from any container.  Collapsibility test for Injectable and Non-Injectable preparation(IP 1996) This test is applicable for those containers. A container by s ueezing yields at least 90% of its nominal contents at re uire flow rate at ambient temperature. R R R M. Reweigh the container. Volume should not exceed that indicated in the table for the type of the glass concerned. Weigh the each container. Allow to stand for 14 days at RH of 60 + 5% at 20 c to 25 c. Keep them inverted at RT for 24 hours.2%. which have to be s ueezed for the withdrawal of product.M. AHMEDABAD ² 09 23 I P I GF PAPER-III NDDS (PART-I) Pha aceu ca Packag ng H Q . Loss of the weight in each container should not be more than 0. y Maximum % of light transmission at any wavelength between 2990nm and 450nm Normal si e(ml) 1 2 5 10 20 50 Flame sealed container 50 45 40 35 30 15 Closure sealed container 25 20 15 13 12 10 Tests on the plastic containers Leakage test for Injectable & Non-Injectable(IP 1996) Fill the 10 containers with water and fit the closure.COLLEGE OF PHARMACY. Water vapor permeability test for injectable preparation(IP 1996) Fill the 5 containers with nominal volume of water and seal.PHARM SEM-II (2009-10) L.Record the volume consumed (corrected for blank obtained by titrating 100 ml of high purity water at same temperature and with the same amount of the indicator).

 Physicochemical tests USP specifies the extracting medium. inverting and applying a vaccum. Total numbers of the fragments should not be more than 10 except butyl rubber where the fragments should not exceed 15.  Fragmentation test Place a volume of water corresponding to nominal volume minus 4 ml in each of 12 clean vials. zinc etc. A poor seal is detected by liquid seeping. y Other changes like PH shift.COLLEGE OF PHARMACY. mass spectrometry. Checking on compression ring seal in cap liner when a system contains a liners. y Heavy metals: This detects the presence of metals such as lead. y Buffering capacity: It measures the alkalinity/acidity of the extract.   Measurement of diffusion coefficient through plastic ‡ ‡ ‡ Stopcock A is first opened allowing evacuation of the system and this gives rise to a barometric leg in the manometer . The height of mercury level indicates diffusion of gas through the plastic. As soon as A is closed. Close the vial with closure and secure caps for 16 hours. discoloration. tin. which may cause the degr dation of a the product should be evaluated. Putting liquid in side pack.M. storing at high temperature and low RH. AHMEDABAD ² 09 24 V W V TS PAPER-III NDDS (PART-I) Pha aceu ca Packag ng U .   Compatibility test Compatibility components will not interact with the dosage form and may not show leaching. Checking of cap removal torque. otherwise purified water is maintained at 70 c. Pierce the closures with 21 SWG hypodermic needle (bevel angle of 10 to 14) and inject 1 ml water and remove 1 ml air. GC -MS etc. gas will diffuse through the membrane and mercury level will increase. Test on Rubber closures  Closure efficiency y y y y y Placing a desiccant in a packed stored under high RH. Count the number of the fragments visible to the naked eye. precipitation. Regular screening is done by liquid chromatography. Repeat the above operation 4 times for each closure (use new needle for each closure). detecting any moisture loss as reduction in weight. M.PHARM SEM-II (2009-10) L. Putting liquid in pack. After the extraction following tests are performed: y Non-volatile residue which measures organic and inorganic residue soluble in extracting medium.

c  Non-destructive type testing y This type of testing equipment is based on a dry pressure vaccum procedure followed by detection of pack distortion (deflection) or non-distortion. It can be detected by wa vapor ter permeation. Wash the vials. packs with effective seals become concave them convex as positive pressur changes to negative pressure.Self sealability test for rubber closure applicable to multidose containers only. i.  Pinholes and package integrity y Pinholes are the common features of aluminium foil. Test for Blister and Strip packaging  Leakage testing and package integrity testing  Mainly two types of testing are involved for checking package integrity. Fill 10 vials with water with nominal volume and close the vials with closure. Tests for Paper and Boards y y y y y y y y Moisture content of paper and board Methods for determining the air permeability Test for the assessment of the odor for the packagi g material n Puncture resistance Roughness/smoothness Brightness Ash in paper and board Ink absorbency M. Apply the vaccum of 33K Pa for strip packages and 24K Pa for blister packs for 30 sec.M. secure the cap. High water vapor permeation indicates the high numbers of the pinholes. Return to the atmospheric pressure and remove the pot from the vaccum chamber. Pierce the caps 10 times at different sites with 21 SWG hypodermic needle.  Destructive type testing Dip the packages in the pot containing the colored water (15-25 c) and place the pot in the vaccum chamber. depending on the scale of the leakage. AHMEDABAD ² 09 25 a b a YX PAPER-III NDDS (PART-I) Pha aceu ca Packag ng ` . Restore the normal pressure and keep the container immersed for 30 mins.e.PHARM SEM-II (2009-10) L. xamine the package for ingress of the water in to the package. Immerse the vials in 0.1% w/v solution of methylene blue under reduced external pressure (27K Pa) for 10 mins. None of the vials should contain trace of colored solution.COLLEGE OF PHARMACY. while e leaking packs either do not change or show less or limited distortion.

Automotive parts. 4. Package is immersed in solution of tracer chemical or dye. Increase in conductivity correlated to presence of liquid near detectors.HIGH VOLTAGE LEAK DETECTION(HVLD) Conductivity of package. Location of leak can be observed. Screw-cap bottles. Helium is used as tracer gas for the detection and measurement of leakage using mass spectrometer. Gas is detected by coulometric detector (O2) or by photoelectric sensor (CO2 OR H2O). M. All types of packages. draw vacuum.ACOUSTIC IMAGING Method Ultrasonic energy is focused in to sample submerged in water or other solvent. large equipments. polymer and foil pouches. insideout method or sniffer probe method is used. -Apply surfactant. package and devices. observe for bubbles. -Submerge package in liquid.LIQUID TRACER TEST Liquid and microbial leakage. AHMEDABAD ² 09 26 .GAS TRACER DETECTION Provides total leakage and permeation information. Package integrity test for Parenteral Preparation Name of the test 1. -Pressure/vacuum or temperature cycling is used to improve the sensitivity. 2. High voltage is applied to sealed container. aerosol (warm water bath test). and look for foaming Test tracer gas is used to measure leakage/permeation across a package seal.COLLEGE OF PHARMACY.M. Information Structural defects visible. Uses Construction materials. 6. applied differential pressure.HELIUM MASS SPECTROMETRY Provides information of microbial and liquid leakage. The carton should spring open in to the square position without the need for unreasonable force. drums. such as channels. blister package.BUBBLE TEST Pipes. pacemakers. vials and syringes. -leakage is detected by dye or chemical. delaminations. 5. Glass and plastic ampoules.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Test for carton  Carton opening force: Hold the flat carton as delivered by its crease between thumb first figure and press. humidity of testing site. 3. Echo patterns produce image of package material.PHARM SEM-II (2009-10) L.

But leakage location can not detected.RESIDUAL SEAL FORCE(RSF) RSF value. aerosols. Vials sealed with elastomeric closures are compressed at constant rate of strain. -Tunable diode laser light is passed through the package. Presence of microbial growth is confirmed visually/ with instrumentation.M. Absorbed light is proportional to contents of oxygen or water.RESIDUAL GAS IONIZATION TEST IR is used to measure the powder moisture inside the unopened glass package. Lyophilized and dry powder.PHARM SEM-II (2009-10) L. Ultrasound echoes are used to create image of heat seals. Pressure/vacuum change greater than nonleaking package is indicative of reject. High voltage. Second derivative of the curve= RSF.PAPER-III NDDS (PART-I) Pharmaceutical Packaging 7. Pharmaceutical industry.COLLEGE OF PHARMACY. 10. Look for leaks. The field causes residual gas to glow. Gaseous contents of residual headspace. validation of package integrity.MICROBIAL CHALLENGE TEST Containers are media filled. Food and medical package devices. sealed container is stored at various stress condition checked over time for weight loss or weight gain. AHMEDABAD ² 09 27 . Contents of oxygen and water. 11.VISUAL INSPECTION leakage 14. Stressstrain deformation curves are generated. vials and syringes. 13. Parenteral packages such as ampoules.VACCUM/PRES SURE DECAY Defects in sealing. Parenteral vials. solid or liquid dosage form packaging. 8. Lyophilized product.ULTRASONIC IMAGING 12. M. Heat seals. Rigidity and porosity of package. and seal is challenged with microorganisms. Leakage.NONINVASIVE MOISTURE AND OXYGEN ANALYSIS 9. Vacuum level is verified by glow or ionization current.WEIGHT CHANGE Filled. Change in vacuum/pressure is measured inside the package or outside in sealed package chamber. Vials. high frequency field is applied to glass vials or bottles sealed under vacuum.

COLLEGE OF PHARMACY. Various EU guidelines applying to packaging are p CPMP list of allowed terms (III/359/91) p Notice to the applicants (updated 1998) p Plastic container guidance (III/9090) p Plastic in contact with food directive (90/128) M. Environmental aspects: p Packaging wastage p Ozone depletion 4.PAPER-III NDDS (PART-I) Pharmaceutical Packaging REGULATORY ASPECTS OF PHARMACEUTICAL PACKAGING:Introduction y FDA ensures the quality of drug products by carefully monitoring of drug manufacturers adhere to pharmaceutical regulatory comlience as per the cGMP. The EU has been fairly successful in the pharmaceutical area while achieving: p Centralized system in place p Decentralized system in place p Harmonization of format p Increase acceptance outside EU.PHARM SEM-II (2009-10) L.M. The following characteristics are common requirements of most regulatory agencies: 1. Label related requirements: p Information to the receiver p Legal control of the product 3. p With the introduction of plastics and tailor made packages . AHMEDABAD ² 09 28 . p Initially glass was used inert no potential interaction with product. European union (EU) represents 30% of the market. The regulatory for over 150 countries may have differing requirements. International conference for harmonization between these areas on certain issues may lead to a further improvement in the situation. Consumer protection: p Child resistant closures p Tamper evident packaging European Union (EU) and its guidelines y Pharmaceutical packaging is a skill based industry directly related with marketing of product. The solution for this lies in the realization of the fact that out of the total market share. Product or preparation related requirements: p Protection of the product p Protection of the consumer p Control of doses 2. US approximately 27% and Japan nearly 18%. & p Harmonization of standards.more scope for interaction between product and package so need more regulation. These ads up to 75% of the market share. y Packaging is also the part of cGMP.

stripes. liner. closures & labels) Packaging further needs to be tamper evident.PHARM SEM-II (2009-10) L. Ozone depletion is also of concern with the use of pressurized containers. y About one third of cost of medicine is accounted for the packaging materials. According to FDA guidelines. The selection of the packaging material of the drug is mainly dependent on the p Nature of product p Machinability p Level of protection required p Shipment requirement p Stability p Dispensing of the dosage form.COLLEGE OF PHARMACY. Environmental concerns: With increased environmental concerns there has been a considerable pressure to reduce contamination of environment with particular concern on amount of packaging & its disposal. etc. As whole plastics. AHMEDABAD ² 09 29 y y y . M. for submitting documents for packaging for human drugs and biological the following are required.PAPER-III NDDS (PART-I) Pharmaceutical Packaging FDA packaging guidelines FDA packaging guidelines defines the types of containers to be used. corrugated boxes. metal & paper are the most commonly used packaging material in pharmaceutical technology. dividing them into p Parenteral containers (glass/plastic) p Nonparenteral containers (glass. jars.) p Secondary packaging (cartons. 2. etc) p Accessories (caps. quality & purity for intended shelflife p Full information needed p Type of container/closure p Suitability for intended use p Submission of packaging information & date. p Cost Basically pharmaceutical packaging is classified as p Primary packaging (bottles. Regarding this aspects the increase in concerns has led to the European E Commission packaging waste directive which requires: y Reduction in quantity of waste y Reduction in harmfulness of waste y Increase in reuse of packaging y Recycling & recovery of packaging waste & y Reduction of the total packaging to be disposed of. glass. strength. Each one has its own pros and cons. child resistant & customer friendly. seal & elastomers when used for closure. Packaging not only provides the protection to the product from contamination & physical damage but also helps in identification of product & display correct information. identity. plastic & metal) p Pressurized containers p Bulk containers of API & drug products Also listed are closures including child resistant & tamper evident closure. 1. cans. blister. Purpose: p Package must maintain standards.M.

The content of active ingredients p For oral liquid preparations in terms of content per single dose.PHARM SEM-II (2009-10) L. volume.I. but only the materials used in the container.P. B. etc. p For liquid parenterals ready for administration 1 ml of percentage by volume or per dose in the case of single dose container. The name of drug p For drug in schedule F or F1 th e given therein p For official drugs letters I.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Legal requirements for labeling and packaging y Under the provisions of the Federal food. AHMEDABAD ² 09 30 . i t is the responsibility of the manufacturer to provide the safety of a packaging material & to get approval before using it for any food & drug products. A material that is not included under GRAS or prior sanctioned & is intended to be used with food. ii. M. if any. must be tested by manufacturer & the data must be submitted to FDA.. According to act labeling & packaging of drug other than homoeopathic medicines is as under: y y y Rule 94.P. The FDA does not approve container as such. Manner of labeling: 1. namely: i.. drug and cosmetic act 1940. Rule 96. dose being indicated in 5 ml. iii.COLLEGE OF PHARMACY. Prohibition of sale or distribution unless labeled: Subject to the other provisions of these rules no person shall sell or distribute any drug. no. measure. Labels on packages or containers of drugs for export shall be adapted to meet the specific requirements of the law of the country to which the drug is to be exported. of units in metric system. p For drug included in National Formulary of India N. but the following particulars shall appear in a conspicuous position on the innermost container in which the drug is packed & every other covering in which that container is packed: a) Name of the drug b) Name. A correct statement of the net contents in terms of weight. The rules & regulations for labeling & packaging under the Drug and Cosmetics Act 1940 are given in the part IX of the act.M. A list of substances considered Generally Recognized As Safe (GRAS) has been published by the FDA. d) Date of expiry.F. Rule 95. the following particulars sha ll be either printed or written in indelible ink & shall appear in a conspicuous manner on the label of the innermost container of any drug & on every other covering in which the container is packed. Subject to the other provision of these rules. Exemption of certain drugs from certain provisions of this part (1). address of the manufacturer and the license number c) Batch or lot no.

hormones. Lic. The particular to be printed or written on the label of mechanical contraceptive shall be as specified in schedule R.M. iv. Every drug intended for distribution to the medical profess ion as a free sample shall bear on the label of the container the words Physician s sample . & X whether covered or not in above list. [provisions of this clause shall not apply to a) Preparation intended for animal treatment b) Preparation intended for external use c) Ophthalmic preparation & ear drops d) Sterile preparation such as sutures. capsules. v. hypoglycemic. For mechanical contraceptives i. viii. of license under which the drug is imported preceded by the words Import License ix.PAPER-III NDDS (PART-I) Pharmaceutical Packaging p For drugs in solid form for parenteral units or weight per milligrams or grams. vii. surgical dressings & preparation intended for parenteral use. AHMEDABAD ² 09 31 . p For other preparation percentage by weight or volume. Drugs specifies in the schedule P and their preparations including combinations with other drugs shall bear on label th e date of manufacturing & expiry date and the period between these two dates shall not exceed that laid down in the said schedule. H. namely: Narcotic analgesics. The figure representing the batch no.] 2. In addition to the other particulars which are required to be printed or written under these rules. sedatives. The name and address of premices of manufacturer. No. pills. or Batch or Lot No. in terms of the content in each unit. A distinctive batch no. p For tablets. antimicrobials. or M. Drugs specified in schedule C(1) & their preparations including combinations with other drugs shall bear on the labels: p The date of manufacture p Date of expiry of potency fixed by the manufacturer p Where such drugs are imported also the No. anticancer drugs & all other drugs falling under schedule G. the label of innermost container of the following categories of drugs & every other covering in which the container is packed shall bear a conspicuous red vertical line on the left side running throughout the body of the label which should not be less than 1 mm in width & without disturbing the other condition printed on the label under these rules. M. antidepresents. or Lot vi. hypnotics.PHARM SEM-II (2009-10) L. tranquillizers. anticoagulants.not to be sold which shall be overprinted. antiepileptic.COLLEGE OF PHARMACY. The figure representing the manufacturing license number being preceded by the words Manufacturing License Number or Mfg. corticosteroids. If any preparation contains not less than 3% by volume of alcohol the quantity of alcohol shall be started in terms of the average percentage by volume of absolute alcohol in the finished products. xi. being preceded by the words Batch No. x. of the license under which the drug is manufactured. etc.L. or B No. Every drug manufactured in India shall bear on its label the no.

indicated this fact on the label & be labeled with the words. 4. b) If it contains substance specified in schedule H be labeled with the symbol Rx and conspicuously displayed on the left top corner of the label & also be labeled with following words: Schedule H drug.M. Rule 97. The container of an embrocating. The container of medicine for internal use shall a) If contain substance specified in schedule G. For animal treatment only & shall bear a symbol depicting the head of a domestic animal.PHARM SEM-II (2009-10) L.PAPER-III NDDS (PART-I) Pharmaceutical Packaging ii. 3. is labeled with the words Caution: it is dangerous to take this preparation except under medical supervision . The container of a medicine made up ready only for treatment of an animal shall be labeled conspicuously with the words Not for Human Use.Warning: To be sold by retail on the prescription of a Registered Medical Practitioner only d) If it contains a substance specified in schedule X be labeled with the symbol XRx which shall be in red conspicuously displayed on the left top corner of the label & be also labeled with the following words: Schedule X drug.Warning: To be sold by retail on the prescription of a Registered Medical Practitioner only 2. lotion. liniment.FOR EXTERNAL USE ONLY M. Labeling of medicines 1. liquid antiseptic or any other liquid medicine for external application shall be labeled with the words in capital FOR EXTERNAL USE ONLY 3. The particulars prescribed in sub rule (1) shall be printed or written in indelible ink either on the label borne by a container or vaccine lymph or on a label or wrapper affixed to any package in which the container is issued for sale.conspicuously printed & surrounded by a line within which there shall be no other words.COLLEGE OF PHARMACY. AHMEDABAD ² 09 32 . 1985 be labeled with the symbol NRx which shall be in red & conspicuously displayed on the left top corner & also labeled with words: Schedule H drug. The following particulars in addition to those specified in subrule (1) shall be either printed or written in indelible ink & shall appear in a conspicuous manner on the label namely: a) Date of manufacturing b) The date up to which the contraceptive is expected to retain its properties c) The storage condition necessary for preserving the properties of the contraceptive up to the date indicated in sub clause (b).warning: To be sold by retail on the prescription of a registered medical practitioner only c) If it containing a substance specified in schedule H & comes within t he purview of the Narcotic drugs and Psychotropic substances Act. The container of a medicine prepared for treatment of human ailments shall if the medicine contains industrial methylated spirit.

7. Nursing Homes. etc. and wrapper enclosing surgical ligature or suture which are nonsterile./ 5 ml. shall bear a label on which are printed or written in a conspicuous manner in indelible red ink the words: Non-sterile surgical ligature(suture). ii. RMPs. Preparations intended for export 5./ 200 ml. The pack sizes of drugs not covered by the schedule P1 shall be as given below: i. Use of letters I. iii.P. obliterate or deface any inscription or mark made or recorded by the manufacturer on the container. The pack sizes for pediatric oral drops shall be 5 ml. Pack sizes of low volume I. v. the pack sizes of tablets/capsules shall contain multiples of. of tablets/capsules is less than 10. or recognized abbreviation of pharmacopoeias & official compendia of drug standards prescribed under these rules shall be entered on the label of the drug only for the purpose of indicating that the drug is in accordance with standards set out in such official books. / 10 ml. The pack sizes for Tablets/capsules shall be where the number o f tablet/capsules shall be where the no.: The letters I. iv. Prohibition against altering inscriptions on containers. Preparations intended for veterinary use 4.M.COLLEGE OF PHARMACY. Non sterile surgical ligature and suture: Every container of . Rule 105. / 100 ml. such packing shall be made by the integral number. Packing of drugs: 1. labels or wrappers of drug: No person shall alter.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Rule 102. AHMEDABAD ² 09 33 . unit dose(including applicaps) 6. The pack sizes for Eye/Nasal/Ear drops shall be 3 ml.V. Pack sizes of dosage forms not covered by the forgoing provisions of this rules 2. / 15 ml.not to be used for operations upon the human body unless efficiently sterilized Rule 104. The pack sizes for liquid oral preparation shall be 30 ml.PHARM SEM-II (2009-10) L. / 450 ml. Physicians samples 8. fluids. The pack sizes of drugs meant for retail sale shall be as prescribed in schedule P1 to these rules. M. The pack sizes for eye ointment shall be 3 gm/ 5 gm / 10 gm. Vitamins / tonics / cough preparations / antacids / laxatives in liquid oral forms. Provided that the provisions of the pack sizes covered under this rule shall not apply to 1. The imported formulations in finished form 3. or numbers above 10. Pack sizes of dosage forms meant for retail sale to Hospitals. label or wrapper of any drug. (pediatric only) / 60 ml. 2.P. / 10 ml. Rule 104A.

5 ml. AHMEDABAD ² 09 34 . iii. No drug may purport or claim to procure or assist to procure.COLLEGE OF PHARMACY. ii. miscarriage in women. 2. in the case of oral liquid preparations. Rule 106. 100 unit doses in the case of tablets/capsules. RECENT TRENDS IN PHARMACEUTICAL PACKAGING:Major influences are: Product trends influencing pack trends Changes and trends in packaging materials Changes in packaging processes Other special considerations.PHARM SEM-II (2009-10) L. in the case of injections. or may convey any idea that it may procure or assist to procure. Diseases which a drug may not purport to prevent or cure (schedule J): 1. No drug may claim to prevent or cure or may carry any idea that it may prevent or cure one or more of the diseases or ailments specified in schedule J. Product trends influencing pack trends M.M. packing of drugs specified in schedule X: The drugs specified in schedule X shall be marketed in packing not exceeding i. 300 ml.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Rule 105A.

Metal containers are showing a much more serious usa ge drop in terms of containers for tablets and capsules. Since under normal handling polyester is much less prone to breakage and is lighter than glass. granules. Under this categor y various grades of PETP and PETG (polyester variants) are steadily growing in use. when the first thermoplastics were used as low M.PHARM SEM-II (2009-10) L.. it is relatively easy to find a plastic which is suitable for a specific product albeit occasionally with a slightly reduced shelf life. Coated and multi -layer plastic containers offer further potential usage for liquid products. AHMEDABAD ² 09 35 . which extends back over several centuries. compared with glass and plastic. the materials which might be considered of historical value are still in wide usage. particularly with reference to retention of certain preservatives. This particularly applies to the use of glass and metal. Although recognised as plastics.PAPER-III NDDS (PART-I) Pharmaceutical Packaging Changes and trends in packaging materials As changes to packaging materials occur relatively slowly. other than aerosol containers. the thermosets play only a minor role as a packaging material and it was not until around 1953 onwards. Silicon dioxide ( glass ) coated plastics are also of interest (SiO2 coatings). A slight reduction in the use of glass has occurred in recent years. and even survival as collapsible metal tubes is doubtful with the advent of laminated tubes. hence this trend could reverse. Although it has been accepted that no one plastic can offer the inertness of glass.M. However. and it is likely that this will continue as a slow downward trend. etc. any cost premium can be readily offset. Rigid aluminium containers. powders. Polyesters generally show good retention of such volatile substances as menthol. esters of salicylic acid.COLLEGE OF PHARMACY. flavours and active ingredients. showed a rapid drop in usage some 8 10 years ago. became unfavourable. camphor. These arebeing closely followed by carbon diamond -like coatings. when costs. ointments. glass is generally seen as environmentally friendly. The conversion of bauxite to aluminium involves high energy levels.

K. E. Joseph L.indiamart.com/pharma-pack machines M. e. solvents. relatively inert to only fair inertness. PET . Machines can handle PE. Germany) and a similar process by Automatic Liquid Packaging (USA) blow fill seal. from highly permeable to ones of low permeability (with reference to moisture. 3 rd edition.. in fact the most economical five.A.).45. by U.com/  www.net/pharmaceutical packaging  dir.g. HOPE. that the real plastic revolution began. AHMEDABAD ² 09 36 . e.  Parenteral quality control.PHARM SEM-II (2009-10) L. LLDPE.pharmainfo. edited by D. Dana Morton Guazzo. and several significant improvements are detailed below. etc. and in certain instances an acceptable compromise may be difficult to achieve. These materials cover a wide range of properties. Dean. some virtually unbreakable. rubber stoppers. etc. 3rd edition. edited by James swarbrick. Special machines can also insert sterile components. edited by Leon Lachman.com/  www. volume4.C. These include the: polyethylenes (PE) LDPE. are clear to very hazy. In 1996 five. 3 rd edition. S.R. In use they usually operate in a clean area but also with a laminar flow type hood over the moulding-filling stations. Output largely depends on the pack size. y Tamper-evidence y Child-resistance References  Pharmaceutical packaging technology.  www. Other special considerations There are occasions when demands or considerations related to a pack conflict. VLDPE polypropylenes (PP) homopolymers and copolymers of polypropylene polystyrenes (PS) crystal and to some extent impact modified polystyrene polyvinylchlorides unplasticised PVC and plasticised PVC polyesters PETP and PETG. Jain. With these precautions the unit can produce sterile non-preserved products. hard. Akers. were the ones most widely used. Evans. brittle to flexible. gases. etc. ULDPE.  The theory and practice of industrial pharmacy. PVC. MDPE. Form fill seal processes for liquids and semi-liquids The Bottlepack system (Rommelag. a range of densities 0. Goupale. Changes in packaging processes In the past 25 years there have many progressive changes in packaging processes.PAPER-III NDDS (PART-I) Pharmaceutical Packaging density polythene squeezee packs.9 1.COLLEGE OF PHARMACY.aclan packaging .continue to be successfully used for pharmaceutical products. by Michael J.  Encyclopedia of pharmaceutical technology.g.M. PP. D. Kanig. Daniel S. nayak. sterility pyrogen. This applies to some of the general observations listed below.  Pharmaceutical packaging technology.karishmainternational. Larrimore. particulate and package integrity testing.