Pharmaceurical Packaging Materials2.pptx

Pharmaceurical Packaging Materials

1. Pha r ma c eut i c al Packa g ing T ec h n o , logy P repa red b y: Jalal U ddin L ect u r e r W or d S c hool o f Ph a rm a cy W orl<I U n i v e r s i ty o f Banglad e s h March 17

2. D e f i 1 n 1 . t 1 . o n Ttie ackaging can be d e fined as the e c onomica l means of providing information , presentat i o n , containment, i nt e grity and stability for d isplay and transportation throughout i ts shelf l i f e . Pharmaceutica l packaging is the science, a 1 1 and technology of enclosing or prot e cting products for distr i butio n , storag e , sale, and us e . Packaging a l so refers to the process of design , ev a luation, and product i on of packa g es. 2 protectio n , c onvenience i dentificatio n , compliance, a product u n til i t during storag e , is consumed or

3. /l Id eal p a c kagi n g r e q ui r e m e n ts They must protect the preparation from environmental condit i ons. They must not be reactive with the product. They must not impa 1 1 to the product tastes or odors. 4 . They must be no n toxic. 5. They must be FDA approved. 6. They n iust 1neet app l icable tamper-resistance J e qu i rernents. 7 . They n iust not be the cause of product d e gradatio n . 8 . They must be adaptable to commonly employed high sp e e d packaging eq u ipment. Mil<eh 1 , 3

4. F ctions of packaging 4 M<1rch 17 Pro d uct Identification: Packaging greatly hel p s in " d e n tification of product s . f roduct Protection: Packaging protects the c ontents o f a product from sp o ilage, bre a kage, l e a kage, etc. Facilitating t h e use of product: Packaging should be convenien c e to open, handle and use for the consumers. Pro d uct Promotion: Packaging is also used for v romotional and attracting the attention of the people while purchasing. M a rketin g : The packaging and l abels can be u s e d by m a rketers to encourage potential buyers to purchase the product.

5. I 5 M<1rch 17 6 . C o n v e n i e n c e : Packages can have fea t u r es that add cqnvenience in d i stribution, handlin g , stacking, d i spla y , s a 1 e , openin g , re-closin g , us e , di s p ensin g , reus e , r e cyclin g , a n d ease of dispos a l. 7 . Barrier pr o t ection: A barrier from oxyge n , water vapor, dus t , etc. , is often required. Permeation i s a crit i cal factor i n design. Some packa g e s co n tain desiccants or oxygen absorbency to help extend shelf l ife. K e e p i ng the contents clean, fresh, ster i le and safe for the intended s h e l f l ife is a prima ry functio n . 8. Secur i t y : Packaging can play an imp o 1 i ant r o l e in r e ducing the security r i sks of shipment. Packag e s can be m ade with improved tamper r e sistance to deter tampering and also can have tamper-evident features to h e l p i n d i cate tamp e r i ng. Packages can be eng i neered to h e l p reduce the ri s ks of package pilfera g e .

6. 6 M<"rch t7 I S e , ection of the P ackagi n g M a terials 1. On the facili t i es a vail a bl e , for example, pressu rized . \ .... _ dispenser r equires spec i al filling equipment. 2. On the ultimate use of prod uct. The prod uct may be used by s killed person in h ospita l or may n e e d to be suita b l e for use in the home by a patient. 3 . On the physical fo r m of the prod uct. For ex a 1 n p l e , sol i d, sem i - so l i d , liqu i ds or gas e ous dosage form. 4. On the rou t e of a d ministra tio n . For exampl e , or a l , parenteral , external, etc. s . On t h e stability of the ma t e ria l . Fo r exam p l e , moistur e , oxygen, c arbon dioxide, l ig h t , trace metal s , t emperature or pr essure or f l u ctuat i on of t h ese m ay h ave a deleterious effect on t h e product.

7. I March 17 7 6. On the contents. The product may react with the package such as the rel e ase of alkali from the glass or y e corrosion of the 1 n etals and i n turn the product i s 8jf f ect e d. 7 . On the cost of t h e produc t . Expensive products usually justify expensive packaging

8. /l M<1rch 17 8 Ha ards encountered by package lfa z J rds encountered by the package c a n be d i vided i nto three main g rou p s. a ) ¥echa n ical hazards b ) Climatic or en v iron m e n tal h azards c) Biol o g i c a l hazard s . The o n l y exception is t h eft, which can be a serious risk with drugs and may demand spe c ial p r otection in certain ca s e s.

9. h 7 a ) M e ch a nical h a z ards: 1. Sho c k i ng or i mpact dam a g e - C o m pression V i b r a t i o n E l ect r i c a l conduct a n ce A bra s i on b ) Climatic or e n v iron m e nt a l h a z ar d s : I. t' i o i s t u r e 2. T e 1 n p e ra t u re 3. Pr e ss u r e .. i . A t m o s ph e r i c g a s e s s. L i g h t 6. S ol id a i r b o r n e conta m i n a n t s.

10. c ) Biol o g ical hazards. l. Microbiologica l haza r ds Che m i c a l h a zards h 7 10

11. T ypes o f packaging March 17 I I Primar y packaging i s the mate r i al that first e n v e lo p s the p rod uct and holds it. This usually is t h e sm a lle s t un i t of distribu t ion or use and i s the pac k age which is in direct c0 n tact w ith the c o n t e n t s. Ex a 1 np l es: Ampou l e s , V ials ,C o ntai n ers , D o s i n g d ropper , C l osures ( p l astic, metal ) , Syringe , St r i p p ackage, Bl i ster packaging.

12. Se c on d a r y pa c k a g i n g is d e fined as the packaging that lies ou side the pri1nary packaging. It i s perhaps used to group pr i mary packag e s togethe r . Example: Paper and board s , Cartons ,C o rrugated fibe r s , Box manufacture ) March 17 12

13. I March 17 13 T ert i a r y packaging i s used for bulk han d l ing , warehouse s t @rage and tra n sport shi p p ing. T he most c o 1 nmon fonn · s a palletized u n i t l oad th a t packs tig h t l y i n to c ont a i ners. ' • , I . I

14. M<1rch 17 A --; J rt from p r imary and s e condary packagin g , two types o f sp e c i a l packaging are currently i n us e , as fo ll o ws: U n " t-dose packaging: This packaging gu a ra n tees safer medication by reducing medication error s ; it i s also more practi c a l for the patient. It may be very useful in improving compl i ance with treatment and m ay also be u seful for l e ss st a ble products. Devi c e packagi n g : P acka g i n g with t h e a i d of an administration device is use r -friendly and also improves c o mpliance. This type of packag i ng perm i ts easier adm i nistr a tion by means of de v i ces such as pre - f i lled syringes, dropper s , transderrna l delivery systems, pumps and aerosol spray s . Such devic e s ensure that the medic i nal product is a d 1 ninistered corr e ctly and in the r i ght a 1 nount

15. T y pes of p a ckagi n g ma t e rials rch 17 15 I ) Gl a s s II) Meta l s I l l ) R ub b e r s IV ) P l a s ti c s C b u C . . l>iM< V) F i b r o u s material P t c ka g ing ) lttrriJJs )f.u l c . . . . . P l u l k C o 1 1 a bi t r bbbt r C t lU.i M r VI) Fi l m s, Foi l s a nd l am i nates

16. Glass • • Gla s s h as been w i d e l y u s e d as a d rug pack a g i n g 1 11ateri a l. ss is composed of s a n d , soda as h , l i 1 11 e st o n e , & c u l l et. • • S i , I A l , Na , K , C a , Mg, Zn & Ba a re ge neral l y used i n to prep a r ation o f glass Adv,antages of glass: T ey a r e h ygienic a nd s u it a ble for st e ri l i z a tion They are relat i ve l y non react i ve ( depending on the grade c h o s e n ) It ean acc e pt a va r i ety of c l o s ures T h ey can b e u sed on high speed packaging l i n es They are tra n sparent. T ey have good prot e ction powe r . 16 11 T ey can be easily labe l e d . M•<eh

17. I M<1rch 17 17 They are availa b l e in various shapes and size s . T ey can withstand the variation in temperature and pressure d u ring sterilizat i on. They are economic a l and easily ava i l able. They are neutral after proper treatment. They can be se a l ed hermet i cally c l osures. They do not deteriorate w i t h ag e . or by removable They are imperm e a b l e to atmosph e r i c mo i sture. gases and

18. Di dv a ntages March 17 18 It is rela t ively heavy Glass is fragi l e so ea s ily broken. R e 1 ease a lkali to aqueous preparation Photosens i tive drug c an not be protect e d in the transparent glass container. Arnber color glass container is required in this case. A s g l ass is a chemical substance, some ti n 1 e it reacts with the product contained ins i de it.

19. T ypes of glass h 7 19 T y p e I ( N e u tral or Bor o s i l i c a te Glas s) T y pe ll ( Treated Soda l i m e g l a s s) T y p e BI ( Soda li1 n e glas s) T y p e N P ( Gener a l pur p ose s o d a l i r n e g l ass ) C olo u r e d g l a ss Neut r a l g l a ss

20. T yp I ( B o rosilic a te Glass ) 2 March t7 88 8 B a J Borosilicate Glass is p rod u ced by replacrng the sodium oxide by boric oxide ( B2 2) and some l ime by alu m i na ( Al203 ) in the basic compon e n ts of glass. , . Least reactive. ).- High melting poi n t and can withstand high temperature. >- Resistan t to chemical s u bstance. ,_ Higher i n gredients and processing cost therefore used f o I more sensitive pharmaceut i cal products such as parenteral or b l ood products. , . M ostly ampoules and vi a l s are rnade up of T ype I g l a ss.

21. T y pe II ( T r e a ted So d a li m e glass ) T ype II glass is made fr o 1n c o 1U 1 nercial soda-l i me glass that n a · been d e -alkalized or treated to remove s u rface alkali. The de-alkalizing process is known as " Sulfur treatment " . Su l f 1 r treatment neutralizes the alka l ine oxides on the surface, rendering the glass more che 1 nically resistant. ;.... Higher chemical resistance b u t not as much as type I. ,. C h eaper than T ype I. > A c ceptable for most products accept blood prod ucts and aqu e ous pharmaceutical with a pH less than 7. 21 M<1rch l7

22. 2 2 March 17 T e III ( Soda l i me glass ) It i s ordinari l y glass prepared from s i l i con d i oxide, soda a s !:\ and li 1 ne stone and is g enerally referr e d to as soda­ li m e g l as s . Glass c ontainers are untrea ted and m a d e of commercial soda-lime gla s s of average or better than average chemical resistanc e . ;... It i s cheapest in qualit y . ;... This types of gla s s i s not suitable for a l kali sensitive products. >- h a s average or s l i ght better than average resistance and is s u itable for non- aqueous parentera l s and non parenteral products. >- T y pe III glass c o n tainers are normally dry sterilized b e fore being f i lled.

23. T J e NP ( General purpo s e s oda lime gl a s s ) March t7 23 g eneral purpose soda- l i me g l ass used for oral and topical preparatio n . It has lowest hydrau l i c resistance and is suitable for solid products, some li q u ids and semi s olids and not for parenteral.

24. C o o ured gla s s March 17 2 4 C o l 0ured glass i s obtained by adding small amounts of metals during fusion of glass. Coloured g l a s s i s used for Light s e nsitive products wh ich does not allow the UV ra y s to pa s s through it. Coloured glass s hould not be used for parenteral preparation because it becomes d i fficu l t to ch e ck clar i ty in such preparations.

25. 1 March 17 Ne u t r al gl a ss It i s another com n 1 ercial var i ety of glass available in be e en soda-lime glass and borosil i cate glass. I . It is res i stant to alkalies 2 . Resista n t to w e athering Withstand to autoclaving It is us e d for the manufacture of multidose vials and transfusion bottles etc.

26. 2 6 Packa g e type Type of fommlation can be packed Minimum qu a l ity of glass that can be used A mpoule Aqueous Any pH lnjeclables of T y p e I Aqueous lnjec 1 ables of pH L ess Than 7 T ype I I Non-Aqu e o u s ln j e c 1 nblcs T ype Ill Vial Aqueous A n y pH lnjec 1 ables of T y p e I Aqueous lnjecwbles of pH L ess Than 7 T ype I I Non-Aqueous lnjec 1 ables l'ype U I Dry Powders F o r Pa r e n t eral U s e (Ne e d T o Be Reco n s tituted Before U s e) March 17 T ype IV

27. Pac k age type T y p e of fonnulation can b e packed Minimum qua l ity of glass that can b e u s e d T 1 1 b l e 1 s . C a p s u l es,. Oral S o li d s & 1 h 1 ' . T S ol i d s l ' or R cco n ' . il i tu tion T ) 'p< I V O m l l i q u i ds (S o l 1 1 1 i o n s.. Susp c ' . n ' . >i o n s, Em u l s ions ) Type I V Bot t l e s and Jars N n s:il & E 11r D rops T ) 'p< I V C cr t 3 i n Types o r l ! x t c ' . fl 1 3 1 T )1 1< I V St : m iiie t l ids ( R ubcf i c i l 'l l t . Loc:al l rr i 1 1 ; u 1 1 s) B l ood & Rc l a u . "d P ro d u c t ii T y p e I A u x il i ary P s e k a g i ng I X - v i ce \Vilh C c rt n i n Kind O f P ro d u c ts D r opper T )1 1< I V A cros Q I 1>rod u c 1 ( s o l u t i o n . Aeros o l con t a i n er s u sp e n sio n . s en 1 is o l i d t y p e ) c n1u l s i o n o r T ) 1 >C I ! Y! ' - ' " 2 7

28. T e d f o r glass materials March 17 2 8 U . S " : P ' . a n d J. P . pr o v i d es two testes to detenn i ne the c h e h u c al resistan c e o f g l ass container s : T es for surface h ydroly t i c r e sistance. T e s t f o r hydro l yt i c r e s i st a n c e of powdered g l a ss.

29. P tic Ma t e rials M<1rch 17 Accordi ng to Br i tish standards i n st i tut e s plasti cs r e presents; " Al wide ran g e of s o l id c o 1npo s i t e materials which are la g e l y o r ga n i c , usually based u pon synthet i c resins or upon i nodifi e d polymers of natur a l orig i n and po s se s sing a p preciable mechan i cal strength. At a s u i t able stage in thei r manufacturi ng, most plastics can be cast, n 1 olded or po l y meriz e d d irectly into shap e " .

30. T J es of plastic materia l s 30 M<1rch t7 P l a s t i c M a t e r i a l s l l l T h e r m o pl a s tic t y p e T h e rm o s e t t i ng t y p e Thermopl a s tic t y p e : On he a ting, they are soften to viscous f l u i d wh ich h ardens aga on coo l i n g . Re s i stant to breakage and ch e ap to p r oduce and p r oviding the r i ght plastics are c h osen w i ll p r o v i de the nec e ssary protection of the p roduct in an attract i ve containers. E.g. polyethylen e , P V C , polystyrene, p o l yP,rop y l ene, p o l ya m i de, p o l ycarbonate.

31. Thermosetti ng type When heated, they m a y b e c o 1 ne flex i b l e but t h ey do not b e come liquid. During heating such m a t e lials form permanent crosslinks betw e e n t h e l i near chain s , r e sult i ng in s o lidification and l o ss of plast i c flow. E . g. P h e nol formaldehyd e , urea formaldehyde , mela n 1 ine formaldehyde . 31 Milrch 17

32. March 17 32 A dv a n t ag e s of pl a s tic m a t eria l s ;... Low i n cost 1..,, L i ght in weight ,.. D u r a ble ,.. P leasant to touch ,. F l ex i ble faci l i tating product dispensing ,.. O d orless and inert to m ost chemicals ,.. Unbreakable ,.. L e ak proof ,.. Able to reta i n the i r shape t h roughout the i r use ,.. T h ey have a unique suc k -back feature, which prevents prod uct d oze. ,.. E a se of transportation T h ey are poor conductor o f heat. T b ey a re resistant to i n organic cbemicals. T h ey have good protection powe r .

33. March 17 33 n J a d v a n t a g e s o f pl a s tic mat e ria l s P l ast i cs appear to have certain d i sadv a ntages l i ke interactio n , adsorpt i o n , absorp t i on lightness and hence po o r physical stabilit y . All are permea ble to some degree to moistur e , oxyge n , c arbon dioxide etc a nd most exh i bit electrostatic attraction, allow pen e t ra t ion of l ight rays u n le s s p i gmente d , b l ack et c . Other n e gati v e f e atu r e s incl ude: St r e ss c racki n g : A phenomenon r e l ated to low den s i ty p o l ythene and certain stre s s cracking agents such as wetting a g ent s , deter g e n ts and some volatile oils.

34. 34 M<1rch 17 O - p : - a l ne l i n g or ca v . i tat i . on: w J 1 ere b y a cont a . mer . mwa r d d 1 ' stort 1 . on or partial collapse ow i ng to absorpt i on c aus i ng swe ll i ng of the pl a stic d i T pling follow i ng a st e am a u toclavi ng operatio n . o t j azing: A s urface r e t i c u l a t i on which can o c c u r par t i cularly w i th p o lystyrene and chemical su b stanc e s ( e. g . isopropyl myrista t e w h i ch first c a uses c r a z i n g and ultima t e l y r each e s of total embitterment and disintegra tion ) . o Poor k e y of prin t : Certa i n plastics su c h as the poly olef i ns n e ed pr e -treating before i nk wi ll ke y . Add i t i ves that migr a te to the surface of the plastic may a l so c ause printi n g problem. o Poor imp a ct res i s ta n ce: Both polystyrene a nd PVC ha v e poor r e si s t a nce. Tliis can be improved by the inclusion of impact modifie r s such as rubber i n case of polystyrene and methy l methacrylate butadiene st y rene for PVC.

35. P91 ( e'ilylene This is u s ed as b i gb and l ow den s i ty pol yethylene L ow d en s ity pol yethy l e n e (LOPE) i s preferred p l as t i c for s q u eeze bot t l es. Propert i e s : Ease of processi ng , barrier to mo i s tur e , st r e n g th / toughnes s , f l e x ib i l i t y , ease of s e a ling. Hi g l1density pol y ethylene C HD P E ) i s l e ss permeable to gas e s and mo r e r esist a nt to oil s , c h e mica l s and s o l v e n t s. Properties: Stiffne s s , st r e ngth I t ou g h n e s s , r e s i stance t o che m i c a l s . It is widely u s ed i n bott l e s for s o lid dosage fo m 1 s. Drawb a c k: prone to s t r ess crack i n g in the p r esence of s u rf a ct a n t s o r vegeta b l e or mine r a l oils. P o l y p r o p y l ene lt bas good r esistance t o c r acking when flexed. Good resis t ance to heat ste r i l i zation. It i s co l orl e ss , odo r l ess themmplastic m a t e r ial wi t h e x c e l l e n t tensile properties ev e n at hig temper ature. Exc e l l ent r esistance to strong acids and a lk a l i s. Low p e m 1 e a bil i ty to water v a p o ur P e rmeability to gases i s intermediate between p o l ye t h yl e ne H D a nd u n - p l a sticiz e d PVC Suitable for u se in clo s u r e s , ta b l et containerS l\JlQ intravenous bottl e s. 3 5

36. Po l yv I ch l o ri d e ( P VC): Mnrch 17 36 V ers a t ili t y , ease of b l ending, streng t h I toughne s s , r e sis t ance t o g r ease / o i l , resis t ance to c h emical s , c l a r i t y. U s e d a s r i g i d p a c k ag i n g m a t e r i a l a nd main c o m p o n e n t of intr a ven o u s bags. Dr a w b ack : Poor impact r e s i s t a n c e wh i c h can be i mproved by addi n g e l ast o m ers t o the pl a s t i cs b i ll i n crease i t s p e n n eab i l i t y. P o l y v i n y l e d e n e c h l o ri d e ( P V D C ) : Exc e l l ent barrier properties against: moistu r e , w a t er v a pou r , UV l igh t , arom a , inorganic acid s , alkalie s , aqueo u s s alt s o lu t i ons, o r g a n i c w a t er s o l ub l e acid s , a l ipha t i c h ydrocarbons , e s t ers of l ong c " a i n fatty acid s , d et e r g e n t base materia l s, e mu l s i f y i n g agents a nd wetting agents. Go o d tl1errnoforrn a b il i t y . PV D tj is very c o s t - effectiv e , as coating w e i g ht can be c ustom i z e d depend ing o n the r equi r ements of the barrier properties. Medica l g r ade and non-toxi c . High l evels of tra n s p arency which i mproves t he a e s thetics of t h e product. P o l yst y r e n e V e r s a t i l i t y , i n s u l atio n , cl a ri t y , ea s i l y fo a m e d ( " Styrofo a m " ). It i also u s e d f o r jars f o r o i n t m e n t s and c rea m s wit h l ow water c o n t e nt. Drawback: C hemica ls lik e i s o propyl m y r i s t a t e produce craz i n g(a f i ne netw o rk of surface crack s ) f o l l owed by weaken i n g and eventu a l l y c o l l a p sib l e of the co n t a i n er.

37. P l a s t ic bonl c s made from P P , HOPE and PS Ma Plastic pou c h es of HDPE B ot t l e - PET and spra y - PP

38. P r o d uct-Plastic i n te r acti o n s March 17 38 P 'rod ct-plastic i nteractions have been d i vided i n to five s e parate c at e gorie s : Per m ea tion L eachi n g Sorption Chemical reaction Alt e ration in the physical propert ies of plast i cs or product s .

39. March 17 39 C o n s titue n t s of pl a s t ic co n t aine r s The residues, addit i v e s, and pro c essing aids that n 1 ay be us e d , therefore possibly extracted from plastic include: ,.. Mo n omer resi dues ,.. Catalysts ,.. Accelerators ,.. S olvents ,.. Extenders ,.. F i llers ,_ Slip additives ,.. An t i-slip ad d i t i v e s ,.. Antistatic agents ,.. A nti- b l ocking agents r Release agents.

40. Milrch 17 T e ;J, f o r plastic c o ntai n e rs Leak test: The p l astic c ontainers (non inject a bles and injecta b l e s ) : F i ll 10 plas t i c c o n tainers with water and fit the closure. Ke e p them i n vert e d at room temperature for 2 4 hours. No sign of leakage shou l d be the r e from any co n taine r . W a e r permeability test: F i ll 5 containers with nominal v o l u m e of water and se a l e d . W eigh e ach containe r . Allow to sta n d for 14 days at r e l at i ve humidity o f 60% at 20 - 25 d e g r e e Ce l s i u s . rewe i gh the containe r . L o ss of weig h t in each c o n tai n e r s h ould not be more than . 2%.

41. M e ta l s Tin 41 March 1 7 Al u mi n u m

42. J tal containers are used s o lely for me d i cin a l products March 17 fo non-parenteral a d 1 ninistration. etal is stron g , opaqu e , impermeable to 1 no isture , gase s , o o or s , ligh t , bacteri a , and shatter p roo f , it is the id e a l packaging material for pressurized contain e rs. ,.. It j s resi stant to h i gh and low temperatures >- They include tube s , packs made fr o 1 n foil or blister s , cans, and aerosol and gas cy l i nders. ;;.. Alum ini u m and stainless ste e l are t h e metals of choice for b o l h pr i 1 nary and s e condary packaging for me d i c i nal product s . >-- Form an excel l ent tamper evident co n tain e r s.

43. AUUMINIUM 43 Milrch 17 l. It is rela t ively l i ght yet strong 2. T i er to l ig h t and chemicals 3 . Impenneab l e and e asy to work into a var i ety of format s , depen d i ng on i ts thicknes s . Thick e s t aluminium is used for r igid co n tainers such as aerosol cans a nd tub e s for effervescent tablet s . In t e rm e dia t e thi c kn ess are when m e chanical integ r i ty is s t i ll i mportant b u t the p ack should be capa b l e of being reformed under a reasonable forc e . e.g. C o l l apsible tubes for semi solid preparations or roll on screw c aps. Th i n n est aluminium is us e d in f l exib l e foil that are usually a c o 1 nponent of la t ninated packaging 1naterial.

44. 1 4 4 M<1rch 17 Disadvantages and their ove r come solution M jor d isadvanta g e is its reac t i vity i n raw state, a l though it ap i d ly f o n ns a protect i ve film of a l u n 1 in i urn oxide i t i s s till lia b l e to co r r osion ( wh e n exposed to some l i quids ano semi solid formul a tion s , particularly at extreme p H or i f the product contains electro l ytes. Over c o m e : T o overcome this problem, A l umin i um is lined with epo x i de, v i n yl or phenolic res i ns. T h ey are w o r k hardening like collapsible tubes are made by impact extrusi o n whi c h tends to m a ke a l um i n iu n 1 le s s f l exibl e . Ove r c o m e : T o overc o 1 n e , fle x i bi l i ty has to restored by an ann e aling stag e .

45. T in T in containers are pr e ferred for foo d , pha n naceuticals and any product for wh i ch pu r i ty is consider e d. T in is the most chemically inert of a ll collapsible metal tubes . Lead: };;> - L e ad has the lowest cost of all tube metals and is widely used for non food products such as adhesive s , i nks. pa i nts and lubr i cants. };;>- L e ad should never be used alone for anything taken int e rn ally because of the risk l ead poison . };> - With i n ternal l i n i n gs, lead tubes are used for products such as c hlor i d e tooth paste. M<1rch 17

46. L . :'1 Milrch 17 1 n 1 ngs I prod uct is n ot co m pa t ib l e w i th bare meta l , the i n terior can be flush e d with wax-type fo n nu l a tion or with resin solu t ion s , although the r e sins or lacquers are usually spray e d on. A tube w i th an epoxy lining costs abo u t 25% more than the s a 1 ne tube uncoat e d. W ax lini n gs are 1 n o st often used with water-based produc t s in tin tubes, and phenoli c , epoxide s , and viny l s are used with aluminium tuoe s , giving better protection than wax, but at a higher co t.

47. ..-, Rubbers ( Elastomers ) : Exc€11ent material for f o r ming s e a ls, us e d to form c l osures s u c li as bun g s f o r v i a l s or in sim i l ar applications such as g a s ets i n aerosol cans. Cat e gories of Rubbers: 1 ) N atural rubbe r s : S u i table for mul t i ple use closures f o r inj e ctable products as rubber r e seals after multiple ins e 1 1 ion o f ne e dle. D i sadvantages are; It doesn't well tolerate multiple autoclaving becoming b r i ttle and leads to relat i ve de g r ee o f extra c t able n lateri a l i n p r esence of ad d i t i ves. i i. Risk of product absorb i ng on or in to a r u bb e r. i i i .It has certa i n degree of moistur e 1 & gas penneation. -11

48. 2 ) " J nth e t ic rub b e r: H ave fewer ad d i tives and thus fewer extractable and t e n ds xperience less sorption of product ingredients. Are less su i t a b l e for repeated insertions of n e edle bec ause they tend to fragment or core pushing small part i c l es of th e b rubber in to the product. e .g. Silicone, but y l , b r o obuty l , chlorobutyl etc. Silicone is least r eactive but it d oes expe r i en c e permeability to 1 n o i sture and ga s . Softer rubbers expe r i e n ce less cor i ng and r eseal bette r , h arder r u bbers are easier to process on high speed packaging lines. M<1rch 17 · •8

49. ib o u s m a t erials The fib r ous materia l s are the important part of pharmaceut i cal packagin g . • • u s m a t e r i a l s include: Papers, Lab e l s, Cartons, Bag s , Outers et c . The A ( pl i cations as well as Ad vantag e s of Cartons in c l ude: ./ Inc r eases display area ./ P rovides bet t er stack i ng for display of stock items v' ssembl e s leafle t s ./ P ro v i des p h ysic a l protection especially to i tems like meta l collap s i ble tub e s . ./ Fi b erboard ou t ers either as solid or co m 1 gated board a l so find substantia l a p l i cation for b ulk s h i pments . ./ R egenerated cellul o s e film, trade nam e s Cellophane & Rayophan e , is used for e ' ther ind i vid ua l car t ons o r to assem b l e a n o . of cartons.

50. 50 M<1rch 17 F ill n s, f oils & l a mi n a t es Cliarac t e risti c s: pplicable to tab l . et s , c apsules , pill s , etc. It ' s a good su b st i tute for PVC sheet. No crackin g , del a m i nation or p i n h o l es It has the qu i te good block i ng prop e 1 ti e s ef f ect i vely protecting d rugs from water vapo r , o x ygen a nd ultraviolet. I t can extend the storage period of drugs. It is particularl y su i table for p acking moistu r e- s ens i tive drugs or those sold in the hot and h u mid a reas. T a k i ng o u t a p a 1 t of the drugs from the drug boards w i thout any impact on other well-packaged drugs. It is u s ed by cold-mould i ng packaging machin e s. It is shaped e asi l y by changing the mold. Nice app e arance can upgrade d rug ' s i mage

51. Blister pack B l i s t er packaging is a type of pre-formed p l astic packaging c otn l non l y u s e d as unit do s e packaging for pharmac e u tic a l s s u c h as t a blet s , Jes or lozenges. Bliste packs consist of two principal componen t s : The cav i ty made from e ither p l ast i c or a l u m iniu m . the Liddin g , 1nade from pap e r b oar d , pape r , plas t i c or a l uminiu m. T he c avity contains the pro d u ct and the l idding se a l s t h e p r oduct in the pa c age. T here are two typ e s of fanning the cavity i n to a base web sh e et: thennofo n 1 1 i ng a n d c o ld f o r m i ng ;( _ .. ; ...._.. March l 7 51

52. T h e 1 oformi n g In the c ase of thennofom 1 i n g , a plastic f i lm or s h e e t i s u n wound from the r e el and guided though a pr e -heat i ng station on the b l i ster line M<1rch 17 5 2 Tbe temperahire of the pre-heat i ng plates ( upper and lower plat e s ) is such that the plastic wi ll soften and become m o l dable. C old formi n g In the c ase of cold formin g , an almninu n 1 -based laminate film ts s i m g l y pressed into a mold by n l e ans of a s tamp. The a l um i num will be elongated and maintain the fonned shape. Advan tage of cold form foil blisters i s that the use of alumi n u 1 n is o ffe p ng a near c omplete barrier for water and oxyge n , allow i ng an extended product expiry date. T h e disadvantages of c old form foil b l iste r s are the slower speed of p r oduction compared to t b ennofor n ung and the lack of transparency o f tile package and the l arger size of the blister c ard

53. M a teria l s us e d in blister p a ckaging 5 3 March 17 P V € (P o l yveny l Chlorid e) P e T F E ( Polyc h loro t ri:fl u r oethylene ) COC ( Cyclic olefin copo l ymers ) PVD C ( Po l yvenyledene c h l o ride ) P P( p olypropylene ) PE ( polyethylene ) , PETg ( glycol-mod i fied polyethylene terephthalate )

54. A d y ant a ges h 7 ' 1 . P r o d uct i n t e g r i ty , P ro d uct protection 3 . T a m p er evidence e d uce p oss i bili ty of accide n t a l 1n i suse Pat i e n t c o mpliance

55. Strip packaging St r i p pac k a g i n g i s a n a l t e r n a t i ve f o rm of pack f o r a un i t dosa g e . It i s a method of e n c l o s ing the product concern e d between t h e two web of 1na t e r ial so that eac h i s contained bet w een se p a rate c o m p a rtJ n e n t. T wo web of m a teria l m a y not be n ec e ssary to be i d enti c al.

56. I t i s common l y used for t h e pac k aging of ta b l ets and 56 capsules. A s n i p package i s f o 1 med by feeding two webs of a ! i eat sealable flexib l e film t h r o ugh a heated cr i mping roller . T h pro d uct i s droppe d i nto the pocket formed before forming the final set of sea l s . A con t i nu o u s strip of packets is formed which is cut to the desir e d n umber of packets in length. The materials us e d for snip p acka g e are cellophane, polyester, po l yethylene, polypropy l ene, p o l yvi n ylchlor i d e.

57. 1 5 7 March 17 C lo s u res Closures a re tbe devi c e s by means of which co n tainers can be °' o p e ned and closed. Pro p e r clos i ng of tbe c o n ta i ner is n e c e ss a ry b e cause It preven t s loss o f n 1 aterial by s p i ll i ng or volati l i zation. It avoids con t am i nation of the product fro n 1 d i r t , microo r gan i sms O[ insects. It prevents deterioration of the product from the effect of the e nv i ron m . ent s uch as moisture , o x ygen or c a rbon dioxi d e. M a terial used for c l osures are; T h e closur e s for conta i ners meant for storage of pharma c e u tical pr oducts are generally made from tbe following basic mater i als. * C ork * G l ass * Plastic *Metal *Rubber

58. Symbols u se d on packag e s and la b els ' ' ' ' ' ' M rch 1 7 58 Fra g ile • This way up Keep aw a y from sunli g h t Keep aw a y from w a ter ® D ANGER P O I SON E XTRE M E LY F LAM M ABLE ! 1 '!If R e c y c l e

59. Quality Assurance Aspects of Packaging T o ensure that patients and consumers receive hig h - quality drugs, the quality management system must take the following considerations into account if the r eqt ired qual i ty of packaging is to be obt a ined: - the requirement s of the national author i ti e s and U 1 e r e l evant legislation - the product - the production process - the manufactu r ers ' internal policies ( safe t y , marketi n g , etc . ). Bad packaging which is the resu lt of deficiencies in the qual i ty a s s urance system for packaging can have s e r i ous consequenc e s , and packaging defects can create prob l ems that may r es u lt i n drug r ecall s . Such defec t s may i nc l ude breaka g e , and problems r e l ating to pr i nting or i nks, or errors on labels and package i J 1 serts ( patient infonuation leaflet s ). The use of GMP and qual i ty control will prevent the r elease of a defective med icinal product. Packagi ng proc e s se s and equ i pment need validatio n / qualification in the s a me wa as any other part of proc e ssing w i thin a pha m 1 aceu tic a l facil i ty. 5 9 M<1rch l7

60. s l pli n g a n d t e s ting o f pack a ging mat e ria l s Sa f li n g f o check the c or r ectne s s of the l abel. pack a g i n g materia l or container referenc e . as well as i n the acceptance of con s i g nmen t s. D e 1 c c 1ing ad u l t ennion of the med i c in a l product, obtaining a sample for retention, et c . The sa111pling pro ced u r e m u s 1 ta k e i 1110 accoun1 1 be ho111o g e nci 1 y and unifonnily of 1 he m a t erial so as 1 ensure 1h a 1 t h e s a m p l e i s r e p r e s e n 1 a1ive of 1h e e n1ire b a t ch. The sam p l i ng p r ocedu r e should be described i n a wrinen p r o t ocol. T e s tin g p r ogramme Q u a l ity comrol tests are i n t ended 10 check t h e i de111 i 1 y of 1 he material concerned. Co111pl e 1 c pltannac o po e i al or an a l o g ous te s t ing 111ay also be carr i ed out, as may spe c i a l tests, where nece s sar y . A ll wri 1 1 en spec i fica t i ons for packaging mate r i als a n d containers sho u l d i nclude 1 e natu r e , e x t ent a nd frequ e n cy of ro u t ine te s t s. Routi n e t ests vary acco r d ing to the t y pe of mate r i a l and i 1 s i mmediate packagin g . the use of the pro d u c t, and 1 h e route of administrat i on. Nevertheless, s uch te s t s usual l y incl u d e the following: - visual i n s p ec t i on (c l eanl i n es s , dcfcci s ) - ests lo identify the 111ateri u l o - i n 1 c n s i onal t es t s - p h y s i cal I CStS S am p l ing i s u s e d ; - chc 1 11ic a l t es1s - m i cro b i o l ogic a l t e sts March 17

61. M<1rch 17 61 P J k a ge validati o n Pac k age validation i nvolv e s two separate validation s : 1 ) -, The design validation of the package as a component of the devic e . D e si g n valida t i on uses evidence to es t ablish what d e sign specifications will confo m 1 with tbe user needs and the intended u s e and 2) The proc e s s va l i dation of the packaging process. Process validation e stablishes by objective evidence t hat a process coDsisten t l y produces a resul t or product that meets p r edetenni ned specifications. The regu latio n , of course, refers t o e stablishing evidence that the man ufacturing steps iDvo l ved in packagi Dg the de v i ce will consistently produce packagi ng wh i ch meets specifications. For exam p l e, the proc e s s capability of packaging and seal i ng e q uipment sho u l d be determined during proc e s s validation and documented . V a l i dation of the package design shall be p e1formed under acnia l or s i mu l ated use cond i tions that show the package conforms to i ts stated intended us e s. Risk an a l ysis shall a l so be in c 1 uded where appropriate.

62. 1 6 2 Mnrch 17 D e sign validation results shall include: the design ide n tification , name of the individual (s) perfonning the valida tion, method (s) used, and the date. Alli of this information should be re c orded in the design h i story file. any significan t change is made i n the p ackaging or packaging operation after validation, the new process will need to be revalidated. One o : the most difficu l t aspects of package validation is deter n 1 i n ing how any samples to test. The goal is not to over test b e cause o f cost con s iderations while still running sufficient tests to provide statistically v a lid satnpling. Statisti c al methods of analysis are impor t a nt i n process validation. The follow i ng d e cision tree from Medical Device and Diagnostic Indust r y , "Str e am l i ning Packag e -Seal V alidation , " October 1992, provid e s various m ethods of statistical analysis. The manufacturer is challenged with detennining which sta t istical method is most applicable to their individual n e ed s . The resulting val i dation p l an should identif y , measure, and evaluate the key proc e ss e s and variables that will require as s es s 1 nent to complete a valid a · on or revalidation of the packaging and the packaging process.