PACKAGING MATERIAL SCIENCE FOR PHARMA PRODUCTS

PHARMACEUTICS

1. Packaging Material Science

2. 1. Protect the contents from the following environmental hazards: Lig h t - protec t the co n tents from lig h t Temperature - be capable of withstanding extremes of temperature. Moisture - be capable of withstanding extremes of humidity. Atmosp h eri c g a se s - pr o tect the co n tents from the effec t of atmospheric gases (e.g. aerial oxidation). Particles - protect from particulate contamination. Microorganisms - protect from microbial contamination. 5

3. 2. Protects the content from the following mechanical hazards Vibration - Usually due to transportation Compression - this usually includes pressure applied during stacking. Shock - such as impact, drops or rapid retardation. Puncture - penetration from sharp objects or during handling operations. Abrasion - this may create electrostatic effects. 3 . T hey must n o t ad d o r per m it loss to i ts cont e nts: Protect the contents from both loss and gain of water. Prot e c t the c ontent s from l os s o f v olat i le m at e rials Mus t no t sh e d parti c l e s into the contents. Must not leach anything to the contents. 6

4. TYPES OF PACKAGING Primary Packaging: This is the first packaging envelope which is in touch with the dosage form or equipment (i.e. bottle, cap, cap liner, label etc). The packaging needs to be such that there is no interaction with the drug and will provi d e pro p e r co n tai n m e n t o f p h armaceutical s . E.g. Blister packages, Strip packages, etc. The main functions of the primary package are to contain and to restrict any chemical, climatic or biological or occasionally mechanical hazards that may cause or lead to product deterioration. Packaging must also function as a m e a n s o f dru g a d ministratio n s . 9

5. Secondary Packaging: This is consecutive covering or package which stores pharmaceuticals packages in it for their grouping. E . g . Carto n s , b o xe s , etc . OR The packaging external to the primary package is known as the sec o n d a r y p a ckagi n g . The secondary packaging mainly provides the additional physical protection necessary to endure the safe warehousing and for refi l l p a cka g ing . 10

6. Apart from primary and secondary packaging, two types of special packagin g ar e curr e ntl y i n use , a s fol l ow s : • Unit-dose packaging . This packaging guarantees safer medication by reducing medication errors; it is also more practical for the patient. It may be very useful in improving compliance with treatment and may also be useful for less stable products. • “Device” packaging. Packaging with the aid of an administration device is user-friendly and also improves compliance. This type of packaging permits easier administration by means of devices such as prefilled syringes, droppers, transdermal delivery systems, pumps and aerosol sprays. Such devices ensure that the medicinal product is administered correctly and in the right amount. 12

7. Types of primary and secondary packaging material Material Type Example of use Glass Primary Metr i c m ed i c al bot t le, ampoule, vial Plastic Primary Ampoule, vial, infusion fluid container, dropper bottle Secondary W rapper to contain primary pack Cardboard Secondary Box to contain primary pack Paper Secondary Labels, patient information leaflet 11

8. CONTAINER: A container for a pharmacopoeial article is intended to contain a drug substance or drug product with which it is, or may be in direct contact. The closur e is a par t o f t h e c o nt a in e r. Q U A L ITIE S O F G O O D C O N T AIN E R : The container must be neutral towards the material which is stored in it. The container must not interact physically or chemically with the substance w h ich it h o lds. It should help in maintaining the stability of product against the environmental fa c tors w hi c h c ause s its d et e r i oratio n . It should be made of materials which can withstand wear and tear during n o rm a l h a n d lin g . It should be made of materials which can withstand wear and tear during n o rma l h a n d ling. It should be able to withstand changes in pressure and temperature. The materials used for making of the container must be non-toxic. 13

9. TYPES OF CONTAINERS: Containers are divided into following types on the basis of their utility: Wel l – close d cont a iner s : A wel l - close d co n tai n er protects the contents from loss during transportation, h a n d lin g , stor a g e o r sale. Single dose containers : These containers are used to supply only one of medicament and hold generally parenteral products. E.g. amp o ule s a n d vials 14

10. Multi dose containers: These containers allow the withdrawal of dose at various intervals without changing the strength, quality or purity of remaining portion. these cont a iners h o ld more th a n o n e d os e a n d ar e use d for injecta b le s . E.g. vials Light-resistant containers: These containers protect the m e dic a m e n t from h armfu l effe c ts o f lig h t. These co n tainers ar e u sed to stor e th o s e medicaments which ar e p h o t o - sensitiv e . 15

11. Air - t i gh t containers : These ar e a lso c all e d hermet i c containers . These containers have air-tight sealing or closing. These containers protect the prod u c t s f ro m dust , moisture an d air . Wher e a s ai r - t i gh t s e al e d contain e rs ar e use d f o r inj e c t able s , ai r - t i gh t c l osed container s ar e meant for t h e stor a g e o f other products. Aerosol containers: These containers are used to hold aerosol products. These containers have adequate mechanical strength in order to bear the pressur e o f aeroso l p a c k ing. 16

12. FACTORS INFLUENCING THE CHOICE OF PACKAGE : 17

13. Legal and official requirement for containers

14. Stability aspects of packaging materials

15. P A C K A G IN G M A T E RIA L S The following materials are used for the construction of containers and closures B o ros i licate glass T r e a ted sod a lime gl a ss R e g u lar sod a - lime glass G e n e ra l p u rp o s e so da lime gl a ss 1 . Glas s : - (i ) Typ e - I (ii)Type-II (iii)Type-III (iv) T y p e - NP (v) Col o ure d gl a ss (i i ) Urea (iv ) Le a d. (i ) P h e n olics (i) P o ly e th y lene (iii)Polyvinylchloride (PVC) (v)Polycarbonate (vii ) P o ly e th y lene terep h th a late M e tals: (i ) Tin (i i ) I r o n (i i i) Al u mini u m Pl a s t ics : (a ) Therm o sett i n g res i ns: (b ) Therm o pl a s t i c res i ns : (ii)Polypropylene (iv ) P ol y s t yre n e (vi ) P o lya m ide (Nylo n ) (PET) 4 . Rubber : (i ) N a tural rub b e r (i i )Ne o pre n e r u b b e r ( iii) Bu tyl rub b er. 19

16. GLASS CONTAINERS: Glass is the prefe r re d p a ckagin g mate r ial. C O MPOS I TI O N O F GL A SS Sand (silicon dioxide) Soda ash (sodium carbonate) Limestone (calcium carbonate) Cullet (broken glass) - aluminium, boron, potassium, magnesium, zinc, barium, Amber: light yellowish to deep reddish brown, carbon and sulp h u r o r iron a n d man g a n es e di o xide Yellow: Compounds of cadmium and sulphur Blue: Various shades of blue, cobalt oxide or occasionally co p pe r (cu p ric ) o xide G r een : iron o xide , man g a n es e di o xid e a n d chr o mium di o xi d 2 e

17. MANUFACTURE OF GLASS: The four basi c processe s use d in the prod u ctio n o f glass are: Blo w ing use s co m presse d ai r f o r m the molten g lass in the cav ity o f metal m o ld. I n drawin g , molten glas s is pulle d through die s or roller s that sha p e the sof t glass. I n pres s ing me c ha n ical force is use d to pres s the m o lten glas s a g ains t the sid e o f a mold. C a sti n g use s gravit y o r centrifug a l force to ca u se molten glas s to form in the cav ity o f mold. 21

18. ADVANTAGES They are hygienic and suitable for sterilization They ar e re l at i v e ly no n rea c t i v e ( dependin g o n the grade chos e n) I t ca n ac c ep t a var i e t y o f c l osures They ca n b e use d o n hig h spee d packagin g l i nes They ar e transpar e n t . They hav e goo d prote c t i o n powe r . They ca n b e eas i ly labe l ed . DISADVANTAGES I t i s re l ati v e l y heavy Glass i s fragile s o easi l y broke n . R e l e as e al k al i t o aq u eou s preparation 22

19. Typ e I gl a ss : Composition: Neutral glass, borosilicate glass (silica (silicon dioxide, SiO 2 ) and boron oxide). Advantages: I t p o s s e s s e s a hi g h hydr o lytic r e si s ta n c e . I t is the most inert type of p harmac e utic a l gl a ss . It has the lowest coefficient of thermal expansion (and hence suitable for sterilization by hea t … .. for amp o ule s and vials ) . Disadvantages: It has very high glass transition temperature so needs complicated processing. And therefore e x pensive . Uses: Type I gl a s s is suit a bl e for p a c k ing al l p harmac e utic a l prep a rati o n s . It is widely used as glass ampoules and vials to package fluids for injection. In contrast to the other types of glass (type II and III), this type has no/little amo 23 unts of basic oxides, so It is used to package solutions that could dissolve basic oxides in the glass.

20. Typ e I I gl a ss Composition: soda-lime-silica glass. Soda (Na 2 CO 3 ) is used to decrease the glass transition temperature of silica. However, soda would increase water solubility of silica, so lime (CaO) is used to increase the hydrolytic resistance. This type would also contain other oxides. Advantages : This glass has a lower melting point than Type I glass. It is thus easier to produce and conseq u entl y chea p er . High hydrolytic resistance due to surface treatment of the glass. Uses: Type II glass used to package aqueous preparations. However, as it contains basic oxides, it is not used to package parenteral formulations with a pH <7 (i.e. acidic); this would increase the pH of the formulation and coul d affec t the dru g stabilit y and p o tenc y . It is the glass used to produce containers for eye preparations and other dropper b o ttle s . 24

21. Type - I I I regula r s o d a l im e glass Containers are untreated are made of commercial soda lime glass of a v era g e ar e b e tter th a n av e rag e c h e m ical res i s t a n c e . It contains high concentration of alkaline oxides and imparts alkalinity to a q u e o u s substan c es. Fl a k e s sep a rat e e a s i ly. Uses: F o r al l soli d d o sag e forms. F o r oil y inje c tions. T y p e N P - g e nera l purp o s e so d a lim e glass Containers are made of soda lime glass supplied for non parental products, inte n d e d for ora l o r to p ical use. Uses: F o r ora l use. Topi c a l purpose. 25

22. PLASTICS According to British standards institutes plastics represents; “ A wid e range o f soli d c o mp o si t e mat e rial s whi c h are largely organic, usually based upon synthetic resins or upon modified polymers of natural origin and possessing appreciable mechanical strength. At a suitable stage in their manufacturing, most plastics can be cast, molded or poly m erize d directl y into shap e ”. 26

23. C l asse s o f plasti c s : There are two classes of plastics, reflecting the behavior with respect to individual or repeated exposure to heating and cooling. Thermoplastics Capable of being shaped after initial heating and solidifying by cooling. Resistant to breakage and cheap to produce and providing the right plastics are chosen will provide the necessary protection of the product i n a n attrac t i v e container s . E . g . Pol y st y rene , poly e th y l e n e an d polyv in y l ch l orid e . Thermosets They n ee d hea t for proc e ss ing i nt o a permanen t shap e . During heat i ng such materials form permanent crosslinks between the linear chains, resulting in solidification and loss of plastic flow. E.g. Phenolic, urea and melamine are representative of thermosets. 27

24. TYPES OF PLASTICS POLYETHYLENE This is used as high and low density polyethylene Lo w densit y polyethylen e ( L D P E ) i s preferr e d plasti c f or sq u eez e bottle s . Properties: Ease of processing , barrier to moisture, strength /toug h ness , fle x ibilit y , eas e o f sealin g . High density poly ethylene (HDPE ) is less permeable to gases and more resis t an t t o oils , chemical s and solvent s . Properties: Stiffness, strength / toughness, resistance to chemicals. I t i s widel y use d i n bottle s for soli d do s ag e forms . Drawback: prone to stress cracking in the presence of surfactant 2 s 9 or vegetabl e or miner a l oil s .

25. POLYPROPYLENE It has good resistance to cracking when flexed. Good resistance to heat sterilization. It is colorless, odorless thermoplastic material with excellent tensile properties even at hi g h te m perature . Excellent resistance to strong acids and alkalis. Low per m eabi l ity to wate r vapo ur Permeability to gases is intermediate between polyethylene HD and un-plasticized PVC Suitable for use in closures , tablet containers and intravenous bottles. POLYSTYRENE Versatility, insulation, clarity, easily foamed (“Styrofoam”). It is also used for jars for ointments and creams with low water content. Drawback: Chemicals like isopropyl myristate produce crazing(a fine netwo 3 r k of surface cracks) followed by weakening and eventually collapsible of the container.

26. POLYVINYL CHLORIDE Versatility , ease of blending, strength / toughness, resistance to grease/oil, resistance to chemicals, clarity. Used as rigid packaging material and main component of intravenous bags. Drawback: Poor impact resistance which can be improved by adding elastomers to the plastics but it will increase its permeability. POLY VINYLEDENE CHLORIDE: Excellent barrier properties against: moisture, water vapour, UV light, aroma, inorganic acids, alkalies, aqueous salt solutions, organic water soluble acids, aliphatic hydrocarbons , esters of long chain fatty acids, detergent base materials, e m ulsifyin g a gent s and w e tting a gent s . Good ther m of o r m a b ilit y . PVDC is very cost-effective, as coating weight can be customized depending on the requirements of the barrier properties. Medica l gr a d e and non - toxi c . High levels of transparency which improves the aesthetics of the product. 31

27. DRUG-PLASTIC CONSIDERATIONS A packaging system must protect the drug without alterin g the co m positio n o f the prod u c t unti l the last dose i s rem o ve d . Dru g - plasti c c o nsiderati o n s ha v e b e e n divi d e d into five categories: Permeation Leaching Sorption Ch e mic a l reaction Alteration 32

28. Permeation: It is the transmission of gases, vapors or liquids through plastic packagin g mater i al. 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 and the taste of the medicinal products may change for the same reason o f p ermeat i on. Leaching: Some plastic containers have one or more ingredients added to stabilize i t , these may l ea c h into the dru g prod u c t . Problems may arise with plastics when coloring agents are added in smal l qu a nti t i e s t o the for m ula. Particular dyes may migrate into the parental solution and cause a toxic effect. 33

29. Sorption: This process involves the removable of constituents from the drug product by the p a c k a g ing material. The therapeutic efficacy of the product may be reduced due to sorption. Sorption may change the chemical structure, pH, solvent system, concentration of active ingredients and temperature etc… Ch e mica l r e activity: Certain ingredients in plastic formulations may react chemically with one or more co m p o nent s o f the dru g pro d uct. Even in micro quantities if incompatibility occurs may alter the appearance of the pl a sti c o r t h e dru g pr o d u ct. 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 p lastics. For example oils have a softening effect on polyethylene, hydrocarbons attack p o ly e thylene a n d PVC. 34

30. METALS Metal containers are used solely for medicinal products for non- pa r entera l ad m inistratio n . Metal is strong, opaque, impermeable to moisture, gases, odors, light, bacteria, and shatterproof, it is the ideal packaging material for pressurize d container s . I t i s resistan t t o hig h and low temperat u res They include tubes, pack s mad e from foil o r blisters , cans , and aeroso l and gas cy l inders . Alu m in i u m an d stainles s stee l ar e the metals of c hoic e for both primary and secondary packaging for medicinal products. Form an excelle n t tamper ev i den t container s . 35

31. ALUMINIUM I t i s relati ve l y l i g h t ye t st r o n g B a r r i e r t o l i g h t an d chemi c als Impermeable and easy to work into a variety of formats, depending on it s thic k ne s s . Thickest aluminium is used for rigid containers such as aerosol cans an d tu b e s for e f f e rvescen t ta b l e ts . Intermediate thickness are when mechanical integrity is still important but the pack should be capable of being reformed under a reasonable force. e.g. Collapsible tubes for semi solid preparations or roll on screw caps. Thinnest aluminium is used in flexible foil that are usuall 3 y 6 a com p o n en t o f lamin a t e d p a ckagin g materia l.

32. Disadvantages and their overcome solution Major disadvantage is its reactivity in raw state, although it rapidly forms a protective film of aluminium oxide it is still liable to corrosion ( when exposed to some liquids and semi solid formulations, particularly at extreme pH or if the product contain s el e ctrol y te s . To overcome this problem, Aluminium is lined with epoxide, viny l or phen olic resins. They are work hardening like collapsible tubes are made by impact extrusion which tends to make aluminium less flexible. To overcome , flexibility has to restored by an annealing stage. 37

33. TIN Advantages: This me t a l is ver y re s is t an t to c hemi c a l atta c k. Readily coats a number of the metals e.g. tin-coated lead tubes combine the softness of lead with the inertness of tin and for this reason it was formerly used for packaging fluoride toothpaste. Disadvantages: Tin is the most expensive metal among tin, lead, aluminium and iron. Uses: Tin containers are preferred for foods, like milk powder containers ar e coat e d w i th t in. Curr e ntl y , som e ey e ointmen t st i ll p ac k aged in pur e tin oin t ment tubes. 38

34. IRON Advantages: Iron as such is not used for pharmaceutical packaging, large qu a liti e s o f t i n - coate d steel , pop u larly calle d ‘t i n’ , com b ines the strengt h o f stee l wit h the c o rrosio n resistanc e o f tin. Disadvantages : If an aqueous liquid can penetrate a pinhole or other fault in the layer of tin, which is virtually a short-circuited galvanic cell is set up and the intense chemical reaction which results brings about rapid corrosion of underlying steel. As a further measure the tin su r face is lacquered. Uses : Fabrication of milk containers, screw caps and aerosol cans. 39

35. LEAD Advantages : Lowest cos t o f al l the m etal s use d in phar m aceutica l contai n ers. Sof t m etal. Disadvantages : Lead when taken internally there is risk of lead poisoning. So lead containers and tubes should always have internal lining of inert metal o r polymer. Uses : With lining lead tubes are used for such product as fluoride tooth paste. 58

36. CLOSURES : A closure is the part of the package which prevent the contents from escaping and allow no substance to enter the container. Closure s a r e availa b le in five b asi c desig n s: Scre w o n , t hrea d e d o r lug Crim p on(crowns) Press o n(sna p ) Roll on and Friction 59

37. Thread e d sc r e w 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. The screw cap is commonly made of metal or plastics. The metal is usually tin plate or aluminum and in plastic is thermoplastic and th e rmoset t ing mater i al. 60

38. Lu g cap: The lug cap is similar to the threaded screw cap and operates o n the sa m e principle. It is simply an interrupted thread on the glass finish, instead of a co n tinuo u s threa d . U n like the threa d e d c losure, it require s o n ly a q u arte r turn. The lug cap is used for both normal atmosphere pressure and vacuu m press u r e closing. 61

39. Cro w n caps: This style cap is commonly used as a crimped closure for beverage bottles. Rol l - o n c l osures The aluminum roll on cap can be seal securely, opened easily and res e ale d e f f e c t i v el y . Resealable, non resalable and pilfer proof types of roll on closures are available for use on glass or plastic bottles. 62

40. Pilfe r proo f closures It is similar to roll on closure but has a greater skirt length. This additional length extends below the threaded portion an d fastened to the b a si c ca p b y the series o f narrow bridges. When the closure is removed the extra portion remains in the space on neck of the container, this indicates that the packa g e ha s bee n o pened. 63

41. CLOSURE LINERS: A liner may be defined as any material that inserted in a cap to effect a seal b e tw e e n the closur e a n d t h e c o nt a in e r. I t is o f t w o typ e s: 1 . H o m o g e neou s li n er These are one piece liners available as disk or a ring of rubber or plastic. It can be withstand high temperature sterilization. 2 . Het e rog e neou s li n ers These are composed of layers of different materials chosen for specific requirements. It consists of facing and backing. Facing is in contact with product and b a c k ing pro v id e s q u estionin g effe c t. 64

42. Factor s i n selec t in g a l i ner: Chemical inertness  should be chemically inert Ap peara n ce , thickness etc. Gas and water-vapour transmission rates  should be low. Torque require to remove the cap  should be optimum. hea t resista n c e  e.g . d urin g aut o clavin g shoul d be thermostable. Shelf-life  should not change their shape during storage. Eco n o m ics  sh o ul d b e cheap. 65

43. RUB B E R S ( E las t om e rs ) : Excellent material for forming seals, used to form closures such as bungs for vials or in similar applications such as gaskets in aerosol cans. Cat egorie s o f Rubber s : 1 ) N atura l rub b er s ; Suitable for multiple use closures for injectable products as rubber re s ea l s aft e r multip l e ins e rt i o n o f ne e dl e . Disa d vantage s ar e ; I t doesn' t wel l tol e rat e mul t iple autoclav ing be c oming brit t le and leads to relative degree of extractable material in presence of additives. Risk o f pro duc t abs o rbin g o n o r i n t o a rub b e r . It has certain degree of moisture & gas permeation. 48

44. 2 ) Sy n th e ti c rubbe r : Have fewer additives and thus fewer extractable and tends to experience less sorption of product ingredients. Are less suitable for repeated insertions of needle because they tend to fragment or core pushing small particles of the rubber i n t o the pr o d u c t . E.g. Silicone, butyl, bromobutyl, chlorobutyl etc. Silicone is least reactive but it does experience permeability to moisture and ga s . Softer rubbers experience less coring and reseal better, harder rubbers are easier to process on high speed packaging lines. 49

45. TYPES OF RUBBER 1 . BUT Y L RUB B ER These are copolymers of isobutylene with 1-3% of isoprene or butadiene. Advantages:- After vulcanization butyl rubber possesses virtually no double bond, consequently they are most r esista n t to a g ing and chem i ca l at t a c k . Permeability to water vapour and air is very low. W a t e r ab s o r p t i on is v e r y low. They are relatively cheaper compared to other synthetic rubbers. Disadvantages Slow decomposition takes place above 130 C. Oil and solvent resistance is not very good. 2 . N I TR I L E RUB B ER Advantages : Oil r esista n t du e to po lar n i t r i l e group. Heat r esista n t. Disadvantage Absorption of bactericide and leaching of extractives are considerable. 50

46. 3 . CHL O ROPREN E RUBBER S (NEOPRENE) T h e s e ar e p o lym e r s o f 1: 4 chlo p r e n e . Advantages Due to the presence of  Cl group close to the double bond so the bond is resistant to oxidation hence these rubbers age well. This rubber is more polar hence oil resistant. H e a t sta b il i ty is g o o d ( u p to 150 C). Water absorption and permeability are less than for natural rubbers. 4 . SILICON E RUBBERS Advantages H e a t r e sista n c e ( u p to 2 5 C). Extremely low absorption and permeability of water. Excellent aging characteristics due to their saturated chemical structures. Po o r tensile str e n g t h . Disadvantages T h e y a r e v e r y e xpensiv e . 51

47. FIBROUS MATERIAL The fibrous materials are the important part of pharmaceutical packaging. Fibrous materials include: Papers, Labels, Cartons, Bags, Outers, Trays For Shrink Wrap s , Laye r Boa r d s O n Pa l let s , et c . The App l ica t i o n s a s w e ll a s Advan t age s o f Cart o n s i n clud e : Incr e ase s d i sp l a y area Provides better stacking for display of stock items As s emble s lea f lets Provides physical protection especially to items like metal collapsible tubes. Fiberboard outers either as solid or corrugated board also find substantial app l ica t i o n f o r bu l k sh i pments . Regenerated cellulose film, trade names Cellophane & Rayophane, is used for eit h e r i n d i vidua l cart o n s o r t o as s embl e a no . o f cart o ns . 72

48. FIL M S F O IL S A N D L A MIN A T E S Regenerated cellulose film based on viscose ( chemical used for manufacturing of rayon) & laminating two or more types of films, cellulose coatings, foil and paper play diff roles such as supportive, barrier, heat sea l & d e c o rative . Fo r Ex a m pl e : Aluminum foil even in the thinnest gauges offers the best barrier properties, which are not approached even by the most impermeable plastics. “Metallization”: A relatively new process whereby particles of metal are laid down onto a surface under vacuum, can significantly improve the barrier properties of a material but these do not approach the properties of a pure foil. In the newer technology “Co-Extrusion”, a number of plastic plies are extruded in combination to produce cheaper laminations. 73

49. Uses o f f i l m s , f o i l s , l a m i na t i o n s : S t r i p packs B l i s ter packs Sachets D i ap h r a g m sea l s f o r bo t t l es Liners for boxes either attached or loose bag-in-box systems & bags. Foi l b l i s ter s : When sealed with a metal foil-cover, the blister can provide a hermetic pack i.e. an isolated system, which excludes any exchange of gases between the product & surrounding atmosphere. Alu-alu foil is the best pharmaceutical packaging film for tablets, capsules, which is taking place of PVC film. App l icab l e t o t a b l ets , capsu l es , p i l l s , et c . It' s a go o d s u b s t i t u te for P V C s h e e t. No crack i n g , delam i na t i o n o r p i nho l es It has the quite good blocking properties effectively protecting drugs from water vapor, ox y ge n an d u l t r avio l e t . It is particularly suitable for packing moisture-sensitive drugs or those sold in the hot and hum i d area s . 54

50. TAM P E R RESI S TAN T PACKAGI N G: The requirement for tamper resistant packaging is now one of the major considerations in the development of packaging for ph a rm a ceutica l pr o ducts. A tamper resistant package is provided with an indicator or barrie r befor e enterin g the package , s o that if this indicator or ba r rie r is br o ken , the b uye r im m ediatel y get s the evidenc e that the pr o duc t ha s b ee n o p ene d o r tam p ered. Especially over the counter products require tamper resistant packaging. 75

51. Th e followin g pac k ag e s ar e ap p rove d b y FD A as tamper resistant packaging systems: Film wrap p ers Blister pa c ka g e Stri p p ack age Bu b bl e pa c k S h rin k seal s a n d b a n d s Foils, p a pe r o r plasti c p o uc h es 76 Bottle seals Tape s eals Break abl e ca p s Se a led tubes A e roso l co n tain e rs Se a led cartons.

52. Fil m wr a p p ers A transparent film with distinctive design is wrapped securely around the entire product container. The film must be cut or torn to remove the product. The wrapper must have an identifying characteristic (e.g. a pattern, name, registered trade mark, logo, or picture) that cannot be readily duplicated. Tinted wrappers are not acceptable as an identifying characteristic because of the possibility that their material may be available to the public. A reasonably tight "fit" of the film around the container must be achieved, e.g. b y a he a t shr i n k type pro c ess. Sealing of a film wrapper with overlapping end flaps is a c c e p ta b le o n ly if the e n d s c a n n o t b e o p e n e d a n d reseal e d with o u t l e a vin g visibl e e v id en c e o f t a m p erin g . The use of cellophane with overlapping end flaps is not a c c e pt a bl e b e c a us e o f the possibilit y t h a t the en d s c a n be opened and resealed without leaving visible evidence th a t ta m p e r i n g h a s o c c u r r e d . 57

53. Although film can be accomplished in several ways and varies in configuration from packaging equipment to packaging equipment, it can be generally categorized in to following types: Fin sea l wrapper En d - fold e d wrapper Shrin k wrapper F i n sea l wrapp er: These seals are formed by crimping the film together and sealing together the two inside surfaces of the film, producing a “fin” seal. The overwrap can be removed or opened only by tearing the wrapper. Materials : Polyethylene or Surlyn (Du Pont’s Ionomer resin) 58

54. End-folded wrapper: This wrapper is formed by pushing the product in to sheet of overlapping film, which forms the film around the product and fold the edges in gift wrap fashion. Film used must be heat-sealable on both surfaces. To be tamper-resistant, the overwrap must be well sealed must be printed or uniquely decorated to exclude the possibility of having an alternate overwrap substituted in its place. The printed surface of the carton being wrapped may also be coated with heat sensitive varnish, which causes overwrap to bond permanently to the paperboard carton during sealing of overwrap. The remo v a l o f t h e o v erwra p w o ul d d e fa c e the c a r t o n , m a kin g the c a r t on u n suitabl e for reuse. Materials: Cellophane coated in both side by heat sealable polyvinylidene chloride (PDVC) or nitrocellulose-PDVC pro v id e s d u rabl e m o i s ture b a r r ier. P o lypro p yl e n e c o at e d wit h he a t seal a bl e a c ryli c c o ating or polypropylene is added with heat sealable modifiers. 59

55. S h rin k wrap p er : The shrin k wr a p concep t involves the p a ckaging of a product in thermoplastic film that has been stretched and oriented during its manufacture and that has the property of reverting back to its unstretched dimensions as the film unwinds on the overwrapping machine, a pocket is formed in the fold of the sheet, in to which the product is inserted. An L shaped sealer seals the remainder of overwrap and trims off the excess film. The loosely wrapped product is then moved through heated tunnel which shrinks the overwrap in to a tightly wrapped unit. Materials: Heat shrinkable grades of polypropylene, polyethylene an d polyvinylchlorid e (PVC). 60

56. Blis t e r p a c k s: It is a packaging configuration capable of providing excellent environmental protection, coupled with an esthetically pleasing an efficacious appearance .it als o p rovid e s use r fu n ctio n alit y in t erm s o f c o n v e ni e nc e , c h ild res i s t a n c e , a n d n o w temp e r res i s t a n c e . The blister package is formed by heat-softening a sheet of thermoplastic resin and vacuum drawing the softened sheet of plastic in to a contoured mold. After cooling, the sheet is released from the mold and proceeds to the filling station of the packaging machine. The semi-rigid blister previously formed is filled with product and lidded with a heat-sealable backing material. The backing material, or lidding, can be of either a push through or peelable type. Dosage units (for example, capsules or tablets) are individually sealed in plastic or foil. The individual c o m p artm e n t m u s t b e torn o r bro k e n to obtai n the pro d u ct. The ba c kin g m a terials c a n n o t b e rea d ily sep a rate d f r o m the blis t er s o r e a s i ly repl a c e d with o ut lea v ing e v id en c e o f t a m p erin g . 61

57. Stri p pack a ge A s t ri p packag e is a form o f uni t dose packagin g o f tablet or capsules. A strip package is formed by feeding two webs of heat sealable flexible film through either a heated crimping roller or a heated reciprocating platen. The product is dropped into the pocket formed prior to forming the final set of seals. Since the sealing is usually accomplished between pressure rollers, a high degree o f s ea l integrity is pos s ible. 82

58. Bubbl e pac k s The bubble pack can be made in several ways but is usually formed by sandwiching the product between a thermoformable, extensible, or heat-shrinkable plastic film and a rigid backing material, this is passed through a heated tunnel, which shrinks the film into bubble or skin over the product, firmly attaching it to the backin g car d . The product and container are sealed in plastic and mounted in or on a display card. The plastic must be torn or broken to remove the product. The backing material cannot be readily separated from the bubble or easily replaced without leaving evidence of tampering 83

59. Hea t s h r i n k b a nd s o r w rap p ers The shrink band concept makes use of the heat-shrinking characteristic of a stretch oriented polymer usually PVC. The polymer is manufactured as an extruded, oriented tube in a diameter slightly larger than the cap and neck ring of the bottle to be sealed. Bands or wrappers with a distinctive design (e.g., a pattern, name, registered trade mark, logo, or picture) are shrunk by heat to seal the union of the cap and container. The seal must be cut or torn to r e m o v e the pro d u ct. The ba n d o r w rap p e r c a n n o t e a s i ly b e w o rke d of f a n d rea p plie d with o ut visible damage to the band. Use of a perforated tear strip can enhance tamper evidence. Cellulose wet shrink seals are not acceptable as the knowledge of how to remove and reapply these seals without evidence of ta m p e r i n g is w id e sprea d . 84

60. Foil, paper, or plastic pouches The flexible pouch is packaging concept capable of providing not only a package that is tamper resistant, but also, by the proper selection of material, a package with a high degree of environmental protection. A flexible pouch is usually formed during the product filling operation by e i ther v e rt i ca l o r horizo n tal forming, f i l l ing, seal i n g (f/f / s ) equipment. The product is enclosed in an individual pouch that must be torn or broken to obtain the product. The pouch should have a distinctive design (e.g., a pattern, name, registered trademark, logo, or picture).The end seals of the pouches cannot be separated and resealed w i thout showin g v i sibl e e v id e nce o f e ntr y . 85

61. Bottl e m o ut h inne r s e als A bottle may be made tamper-resistant by bonding an inner seal to the rim of the bottle in such a way that access to the product can only be attained by irreparable destroying the seal. Various inner seal compositions may be used like: Glas s ine a n d foil laminati o ns. Glue m o u nted. Pressure sensitive adhesive. H e a t s e nsitiv e a d hesiv e . Paper, thermal plastic, polystyrene foam (except those applied with pressure sensitive adhesive), plastic film, foil, or combinations thereof, with a distinctive design (e.g., a pattern, name, registered trademark, logo or picture) is sealed to the mouth of a container under the cap. The seal must be torn or broken to open the container and remove the product. Seals applied by heat induction to containers appear to offer a higher degree of tamper evidence than those that depend on an a d hesiv e to cr e at e the b o n d. To meet tamper-resistant criteria, the inner seal must be printed or decorated with unique design. The seal must also be bonded sufficiently to ensure that its removal wo u ld r e sul t in destructio n o f the s e al. 66

62. Tap e seals Tape involves the application of a glued or pressure sensitive tape or label around or over the closure of the package, which must be destroye d to g a in ac c es s to the p ackage d pr o duct . T h e p a pe r used most often is high density lightweight papers with poor tear strength. Paper or foil with a distinctive design is sealed over all carton flaps or a bottle cap. The seal must be torn or broken to remove the product Tape seals are acceptable only if they contain a unique feature that makes it apparent if the seals have been removed and reapplied , e.g. , a perma n en t ad h esi ve. 87

63. Br e a k a b l e c a ps Breakable closures come in many different designs. The roll on cap design use d in t h e p a s t for c a rbo n at e d b e v e rag e s use s a n al u min u m she e t, w h ich placed over bottle neck during capping operation. The cap blank is held on the bottle under pressure while rollers crimp and contour the bottle tread into the cap blank. The bottom portion of cap is rolled around and under the locking ring on the bottle neck finish. This lower portion of the cap blank is usually perforated so that it breaks away when the cap is unscrewed, which serv e s a s v is i bl e sig n o f prio r o p e n in g . A ratchet-style plastic cap is also commonly used for a number of different products. In this design the bottom portion of closure has a tear-away strip, which engages a ratchet on the bottle neck. To remove the closure, the bottom portion of the closure must be torn away to disengage the ratchet and allow the remo v a l o f t h e c a p. 88

64. Sealed metal tubes or plastic blind-end heat 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 those products that require high degree of barrier protection afforded by metal. Puncture inserts, which are usually made of aluminum 3 to 5 mil thick, are used to seal the tube opening for tamper resistance. Both ends of the tube are sealed. The mouth or blind-end must be punctured to obtain the product. A tube with a crimped end is acceptable if the crimped end cannot be breached by unfolding and refolding without showing visible e v id en c e o f t a m p e r i n g . Direct printin g o f t h e la b e l o n the c o nt a in e r is preferred to using a label that could be removed and substituted. 89

65. Card b oa r d cartons Folding paperboard cartons have been used as secondary package for OTC products for many years. Seal end cartons uses externally ap p lied glu e o r h o t melt to p r ovid e carto n sealing. Cardboard Cartons specifically designed to ensure that in order to obtain the product, the carton seal must be cut or must be non- resealable without showing visible evidence of en torn to remove the product and must not be able to be easily worked open and reseal e d withou t o b viou s da m ag e t o t h e carton. 90

66. A eroso l c o ntai n ers The aerosol container used for pharmaceutical products is usually made of drawn aluminium. The inside of the container can be specially coated if pro d u c t c o m p atibilit y is a pro b le m . A hydrocarbon propellant in its cooled liquid phase is added to the container along with the product, and a spray nozzle contained in a gasketed metal ferrule is crimped over the opening of the aerosol container. A length of polyethylene tube, called a dip-tube, is attached to the inside of the spray nozzle and dips into the product, drawing product into the spray nozzle when the spray e r is a ctiv a ted. The spray nozzles are usually metered to allow a specific dose to be dispersed wit h ea c h spray. 91

67. QUALIT Y CONTRO L TEST S FO R GLASSES CHEMICAL RESISTANT OF GLASS CONTAINERS POWDERED GLASS TEST: It is done to estimate the amount of alkali leached from the powdered glass which usually happens at the elevated temperatures. When the glass is powdered, leaching of alkali is enhanced, which can be titrated with 0.02N sulphuric acid using methyl red as an indicator Step-1 : Preparation of glass specimen : Few containers are rinsed thoroughly with purified water and dried with stream of clean air. Grind the containers in a mortar to a fine powder and pass through sieve no.20 and 50. Ste p - 2 : W a s h in g th e spe c ime n : 1 g m o f t h e a b o v e spe c im en is ta k e n into 250 ml conical flask and wash it with 30 ml acetone. Repeat the washing, decant the acetone and dried after which it is used within 48hr. Procedure: 10gm sample is added with 50ml of high purity water in a 250ml flask. Place it in an autoclave at 121 ⁰ C±2 ⁰ C for 30min.Cool it under running water. Decant the solution into another flask, wash again with 15ml high purity water and again decant. Titrate immediately with 0.02N sulphuric acid using methyl r 7 e 2 d a s a n i n d icat o r a n d r e c or d the v o lu m e.

68. PREPARATION OF SPECIMEN FOR POWDERED GLASS TEST 93

69. POW D ERE D GLAS S TE S T (Acc ord i n g t o US P volum e 27) 94

70. B ) W A T E R ATTAC K T E ST: This is only for treated soda lime glass containers under the controlled humidity conditions which neutralize the surface alkali and glass will become c h e m ically m o r e res i s t a n t. Principle involved is whether the alkali leached or not from the surface of the container. Procedure: Rinse thoroughly with high purity water. Fill each container to 90%of its overflow capacity with water and is autoclaved at 121 ⁰ C for 30min then it is cooled and the liquid is decanted which is titrated with 0.02N sulphuric acid using methyl red as an indicator. The volume of sulfuric acid consumed is the measure of the amount of alkaline oxides present in the glass containers. TESTS CONTAINER VOL.OF 0. 2 N H2SO4 P o w d e re d g l a s s t e st Type I Type II Type I I I 1.0 8.5 15.0 Wa t e r a t t a c k t e st Ty p e II ( 1 0m l o r below) Type I I (abo v e 1 0ml) 0.07 0.02 95

71. WATER ATTACK TEST (USP) 96

72. 2 ) HYD R O LYT I C R E SIS T A N C E O F G LA S S C O N TA I N E RS: Rinse each container at least 3 times with CO 2 free water and fill with the same to their filling volume. Also fill & Cover the vials and bottles and keep in autoclave. Heat to 100 ⁰ C for 10min and allow the steam to issue from the vent cork. Rise the temp from 100 ⁰ C to 121 ⁰ C over 20min. Maintain the temp at 121 ⁰ C to 122 ⁰ C for 60min.Lower the temp from 121 ⁰ C to 100C over 40min venting to prevent vacuum. Remove the container from autoclave, cool and combine the liquids being examined. Measure the volume of test solution into a conical flask and titrate with 0.01M HCl using methyl red as an indicator. Perform blank with water and the difference between the titration represents the volume of HCl consumed by the test solution. Nom i nal capa c ity o f containe r (ml) Numb e r o f containe r s to be used Vo l ume o f tes t so l ution t o be used or titra ti o n (ml) Up to 3 a t least 20 2 5.0 5 o r l ess a t least 10 50.0 6 to 30 a t least 5 50.0 More t h a n 30 a t least 3 100.0 97

73. 3 ) A R SENI C TEST: This test is for glass containers intended for aqueous parenterals. Wash the inner and outer surface of container with fresh distilled water for 5min.Prep test as described in the test for hydrolytic resistance for an adequate no. of samples to produce 50ml.pipette out 10ml solution from combined contents of all ampoules to the flask. Add 10ml of HNO3 to dryness on the water bath, dry the residue in an oven at 130 ⁰ C for 30min cool and add 10ml hydrogen molybdate reagent .Swirl to dissolve and heat under water bath and reflux for 25min. Cool to room temp and determine the absorbance at 840nm.Do the blank with 10ml hydroge n mol y bdate . The absorbance of the test solution should not exceed the absorbance obtained by repeating the determination using 0.1ml of arsenic standar d solut i o n (10 p pm ) in plac e o f t e s t soln. 79

74. 4 ) T H ERMA L SH O C K T EST: Place the samples in upright position in a tray. Immerse the tray into a hot water for a given time and transfers to cold water bath, temp of both are closely controlled. Examine cracks or breaks before and after the test. The amount of thermal shock a bottle can withstand depends on its size, design and glass distribution. Small bottles withstand a temp differential of 60 to 80 ⁰ C and 1 pint bottle 30 to 40 ⁰ C. A typical test uses 45C temp difference bet w ee n h o t a n d col d w a ter. 5 ) INTERNA L BURSTIN G PRESSUR E T EST: The most common instrument used is American glass research increment pressure tester .The test bottle is filled with water and placed inside the test chamber. A scaling head is applied and the internal pressure automatically raised by a series of increments each of which is held for a set of time. The bottle can be checked to a preselected pressure level and 80 the test continues until the container finally bursts.

75. 6 ) LEAKA G E TE S T: Drug filled container is placed in a container filled with coloured solution (due to the addition of dye)which is at high pressure compared to the pressure inside the glass container so that the coloured solution enters the container if any cracks or any breakage is present. 7 ) AN N EALIN G TE S T: The sample is examined by polarized light in either a polariscope or strain viewer. The strain pattern is compared against standard discs or limit samples. 8 ) VERTICA L L O A D TE S T: The bottle is placed between a fixed platform & a hydraulic ramp platform which is gradually raised so that a vertical load is applied. The load is registered on pressure gauge. 9 ) AU T OC L AVIN G (12 1  C fo r 6 min) Ability of a filled or empty container to withstand autoclaving may be checked. 81

76. QUALITY CONTROL TESTS FOR PLASTICS: 1 ) LEAKAG E TE S T: Fill 10 containers with water, fit with intended closures and keep them inverted at room temperature for 24hr.The test is said to be passed if there is n o s i g n s o f le a k a g e f r o m a n y c o nt a in e r. Leakage test for plastic containers (non-injectables & injectables 1996 IP): Fill 10 plastic containers with water and fit the closure Keep them inverted at room temperature for 24 hrs No sign of leakage should be there from any container 102

77. 2 ) C O L L A P S I BILIT Y T EST: This test is applicable to the containers which are to be squeezed for removing the contents. A container by collapsing inward during use, yield at least 90% of its normal contents at the required rate of flow at ambient temperature. 3) WATER PERMEABILITY TEST FOR PLASTIC CONTAINERS (INJECTABLE PREPARATIONS IP 1996): 103

78. 4 ) CL A R I T Y O F A Q U E O U S EX TRACT: Select unlabelled, unmarked and non laminated portions from suitable containers, taken at random. Cut these portions into strips, none of which has a total surface area of 20sq.cm.Wash the strips free from extraneous matter by shaking them with at least two separate portions of distilled water for about 30sec. In each case and drain off the water thoroughly. Thus processed sample is taken in to the flask, previously cleaned with chromic acid mixtures and rinsed with several portions of distilled water and added 250ml dist water. Cover the flask and autoclave at 121 ⁰ C for 30min.Carry out the blank determination using 250ml dist water. Cool and examine the extract, it should be colo u rl e s s a n d f r e e from turbi d ity. 5 ) TR A NSPA R EN C Y TEST: Standard suspension preparation : 1gm hydrazine sulphate in 100ml water and set aside for 6hr. Take 25ml of this solution and add 25ml of 10%w/v hexamine and stand for 24hr. Test solution preparation: Sample is prepared by 16fold dilution of the standard suspension. Fill 5 containers cloudiness detectable when compared to water filled 84 containers. Absorbance is measured at 640nm and the range is within 0.37 and 0.43.

79. BIOLOGICAL TESTS: Sy s t e m i c Inject i o n T e s t : Test an i m a l – A l b i n o M i ce Inject each of 5 mice in test group with sample or blank observe the animals i m media t ely , aga i n a f ter 4h r & t h e n a t 24 , 48 , 72h r s. If none of animals shows significant greater biological reactivity than the blank the sample meets the requirements. Limit - If abnormal behavior such as Convulsion or Prostration occurs or if body weight loss is greater than 2g, the sample does not meet the requirements. Int r a C u t a ne ou s Test: Te s t an i ma l - Rab b it Examine the sites of for any tissue reaction like erythema, oedema, neuosis at 24, 48, 72 hou r s a f ter in j e c t i on. Limit - difference between the scores of sample and blank should be lesser than 1.0. E y e Ir r i t a t i o n Tes t O n Rabbi t s: Te s t an i mal - a l b i n o ra b b i ts Limit - Sample extract shows no significant irritant response during the observation period 85 with blank extract.

80. QUALITY CONTROL OF CLOSURES PREPARATION OF SAMPLE(SOL.-A): Wash closures in 0.2%w/v of anionic surface active agents for 5min.Rinse 5 times with dist water and add 200ml water and is subjected to autoclave at 119 to 123 ⁰ C for 20 to 30min covering with aluminum foil. Cool and separate solution from closure (soln-A). 1 ) STE R IL I T Y TEST: When treated closures are subjected to sterilization test at 64-66 ⁰ C and a pressure of a b o u t . 7 K Pa for 2 4 hr. 2 ) R E SI D U E O N E V AP O RAT I O N : 50ml of solution A is evaporated to dryness at 105 ⁰ C.Then weigh the residue NMT 4mg. 3 ) PE N ETR A BIL I TY: This is measured to check the force required to make a hypodermic needle penetrate easily through the closure. It is measured by using the piercing machine. The piercin g force must n o t e x c e e d a s tated value . I f it e x c e ed s th a t state d v al u e , the hypodermic needle can be damaged as a result of undesirable hardness of the closures. 86

81. 4 ) FR A G ME N TA TIO N T E ST: 107

82. 5) Self – sealability: This test is applicable to closures intended to be use d wit h water. 108

83. 6 ) p H O F A Q UE O U S EX T R AC T: 20ml of solution A is added with 0.1ml bromothymol blue when it is added with a s m a ll a m o u n t o f 0.0 1 M N a OH w h ich c h a n g e s the c o lo u r f r o m bl u e to y ello w . The volume of NaOH required is NMT 0.3ml and if it is done with HCl, the v o lu m e o f HCl n e e d e d sho u ld NM T . 8 m l. 7 ) LIG H T ABSO R P T IO N T E ST: It must be done within 4hrs of preparing solution A. It is filtered through 0.5μ filter and its absorbance is measured at 220 to 360nm. Blank is done without closures and absorbance is NMT 2.0. 8 ) R E D U CI N G SU B ST A NC ES: 20ml of solution A is added with 1ml of 1M H2SO4 and 20ml of 0.002M KMnO4 and boil for 3 min then cool and add 1gm of potassium iodide which is titrated with sodium thio-sulphate using starch as an indicator. Blank is don 89 e and the difference between titration volumes is NMT 0.7ml.

84. QUALITY CONTROL OF COLLAPSIBLE TUBES 1 ) LEAK A G E T E S T : Water was filled in the tube and tightly closed. External surface was wiped off and tube is kept inverted on filter paper at base. Allow to stand for 1hr.Filterpaper shows a b sorpti o n a t a n y time d u rin g te s t period. LACQUE R CUR I N G TEST: P o we r o f ad h e s i o n: Tube was spitted along the length and flattened. Cotton wool soaked in acetone was rubbed over lacquer surface for 20min.Lacquer should not lift from surface and cotton wo o l sha l l r e main colorles s . B ) Flexi b il i t y te s t: The tube was folded in such a manner that internal lacquer surface is outside. The lacquer coating should not be peeled off when the folded position is rubbed with finger. 3 ) LACQUE R COMPATIBILIT Y TES T : 10 tubes are taken for the test. Product was filled and crimped subjected to 45 ⁰ C for 7 2 hr. T u b e s w e r e a l l o w e d to coo l a n d cu t leng t hw i s e . Pro d uc t co m p a ti b ilit y : Content should not show any discolorations or change in colour or gas formation. B ) Lacq u e r co m p a ti b ilit y : L i ft i n g o r pe e li n g o f l a cque r is ch e c k ed. 90

85. QUALITY CONTROL OF METALLIC TINS 1 ) D ESCRIP T ION: Metallic tins having smooth inner surface. The upper surface is sealed consists a clip to break the seal. The lower surface is open. 2 ) DIM E NSIO N S: Height- Measure the height in mm of 10 metallic tin, individually from the lo w e r sur f a c e e d g e to t h e u p p e r r i m. Limit - Specimen metallic tins with tolerance-170mm±10mm. 3 ) DIA M ET ER : Inn e r di a m e ter - Me a sur e the in n e r di a m e ter o f 1 meta llic tins. Limi t - NL T 98 m m. O uter di a m e ter: Limi t - N M T 1 5 m m. 4 ) C L E A N L INES S CH EC K: It should not be dirty, damaged, stained or consist of any foreign particles. 91

86. QUALI T Y CONTRO L O F STRI P AN D B LISTERS Procedure: 3/4th of water is poured in desiccators. The strips and blisters were placed inside the desiccators and vacuum is applied. After sometime vacuum was released and strips, blisters were taken out. The water present over the outer surface of the packages was wiped off with tissue paper. The contents of strips and blister packages were removed and the presence of moisture was checked. If there is no leakage, the contents will not be wetted. This indicates the p e r f e c t sealin g o f t h e p a c k a g es. 92

87. QU ALI T Y CONTRO L TEST S FO R CA R TO N S: Compression: This method is used to assess the strength of erected package. Carton opening force: The method is used to hold the flat carton as de l i v ered , b y i t s creas e s be t w e e n thumb & first finger press. Coefficient of friction: Both static & kinetic coefficients of friction are determined by sliding the specimen over itself under specific test conditions. Crease stiffness: This involves testing a carton board piece & folding it through 90  . It will then try to recover its former position when bendin g for c e is remov e d. Joint shear strength: This is a method of testing the glued lap seam on the side of a carton for strength of the adhesive using a tensile testing machine. 93

88. Q U AL I T Y C O N TR O L O F PA P E R A N D B O AR D The tests pieces of paper and board are conditioned for the tests to be carried out in standard conditions. They are: Te m perature : 2 3 ⁰ C ± 1 ⁰ C Relative h u midity: 5 % ± 2 % . S o me o f the tests to b e p e r formed are: 114

89. 115

90. 116

91. 117