Unit-2-1-Tablets-PPT.pptx

Types of Tablets, Formulation Exciepients of Tablets, Manufacturing of Tablets, Quality Controle Parameters of Tablets, Processing Problems of Tablets

1. TABLETS Mr.B.Brahmaiah Assistant Professor Department of Pharmaceutics Shri Vishnu College of Pharmacy, Bhimavaram

2. INTRODUCTION Tablet is defined as a compressed solid dosage form containing medicaments with or without excipients. According to the Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drug or a m i xt u r e o f dr u g s , with o r without diluents

3. The advantages of the Tabletdosage form are: Th ey a r e uni t d osa g e f orm and of f er th e g r e a t e s t capabil i t i e s o f all o r a l d osa g e f orm f or th e g r e a t e s t d o se p r ecision and th e least c o n t e n t v a ri a b i l it y . C os t i s l o w es t of all o r a l d osa g e f orm. L i g h t e r and c ompa c t. Easiest a n d cheapes t t o pa c ka g e a n d s tri p . Easy t o s w all o w i n g with least t en d en c y f or ha n g -u p . Sustained release product is possible by enteric coating.

4. Object io n a bl e o d our and b i t t e r t a s t e ca n b e mas k e d b y coating technique. Sui t a bl e f or l a r g e scal e p r o d u c t io n . G r e a t e s t chem i ca l and mi c r ob ia l st a bil i ty o v e r al l o r a l d o s a g e f orm. Product identification is easy and rapid requiring no additional steps when employing an embossedand/or m o n o g r amm e d punc h f a c e .

5. Disadvantages of Tablet dosage formare : Dif f icu l t t o s w a ll o w in c as e of c h i l d r e n a n d u n c o n sc io u s patients. Some drugs resist compression into dense compacts, owing to amorphous nature, low densitycharacter. Dr u gs wi t h poo r w e t t i n g , sl o w di ss o l u tio n p r o p e r tie s , opti m um absorp t i o n h i g h i n GIT m a y b e di f f icu l t t o f o r m u l a t e or manufacture as a tablet that will still provide adequate or full drug bioavailability. Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating. In such cases, capsule may offer the best and lowest cost.

6. D i f f eren t types of T a b l et s T a bl e t s i n g e s t e d o r al l y : C om p r e ss e d tablet , e . g . P a r a c eta mo l tablet M ul t ipl e c omp r e ss e d tablet R e p e a t action tablet D e l a y e d r elease tablet , e . g . E n t e r i c c oa t e d B i sa c o dy l tablet Sug a r c oa t e d tablet , e . g . M ul t i v i tam i n tablet F i l m c oa t e d tablet , e . g . M e t r o n i d a z ol e tablet C h e w a b l e tablet , e . g . Antaci d tablet T a bl e t s use d i n o r a l c a v i t y : B u c c a l tablet , e . g . Vi t ami n -c tablet Sublingual tablet , e . g . Vicks M e n t h o l tablet T r och e s o r l o z e n g e s Dental c on e

7. T ab l et s a d m i n i s t e r e d b y oth e r r o u t e : Imp l an ta tio n t ab l e t V agi n a l t ab l et , e . g . C l otrim a z o l e t ab l e t (D ) T ab l et s use d t o p r e p a r e s o l u tio n: 1. E f f e r v e s c e n t t ab l et , e . g . Dis p iri n t ab l e t (Aspirin) 2. Dispensing tablet, e.g. Enzymetablet ( D igip l e x ) H y p ode r m i c t ab l e t T ab l e t t r it u r a t e s e . g . Enzyme t a bl e t ( D igiplex)

8. Ta b l e t Ingred i en t s In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Differentexcipients are: Diluent Bin d er a n d a d h e s i v e Disintegrents Lubrican t s a n d g lidan t s C o l o ur i n g a g e n t s F l a v o r i n g a g e n t s S w ee t e n i n g a g en t s

9. EXCIEPIENTS- functions Impart weight, accuracy, & volume(its allow acccuracy of dose) I mp r o v e so l ubil i t y I nc r e as e stability E n ha n c e b i o a v a i l a b i l i t y M o d i f yin g dr ug r elease Assi st pdt id e nt i f ic a t i on I nc r e as e pat i ent a cc e p t ab i l i t y Facilitate dosage formdesign

10. 1. Diluent: Diluents are fillers used to make required bulk of the tablet when the drug dosage itself is inadequate to produce the bulk. Secondary reason is to provide better tablet properties such as improve cohesion, to permit use of direct compression manufacturing or to promote flow. A dilue n t shou l d h a v e f o ll o w i n g p r oper ti e s : Th ey mus t b e n o n t o x i c Th ey mus t b e c omm e r c i a l l y a v a i l a b l e in a cc e p t ab l e grade Th e r e c o s t mus t b e l o w Th ey mus t b e p h y s i o lo g i c al l y ine rt Th ey mus t b e p h y s i c al l y & c h e m i c al l y stable b y themselves & in combination with thedrugs. They must be free from all microbialcontamination. Th ey d o n o t al t e r th e b i o a v a i l a b i l i t y of dr u g . They must be colorcompatible.

11. C o mm o n l y us e d tablet di l u e nt s Lactose-anhydrous and spray dried lactose D i r e c t l y c omp r e ss e d s t a r c h -S t a R x 1 5 Hydrolyzed starch-Emdex and Celutab Mic r oc r y sta l l i n e c e llul o se- A v i c e l ( P H 10 1 a n d P H 1 2 ) Dibasic calcium phosphatedehydrate Calcium sulphatedihydrate Mannitol Sorbitol Sucrose- Sugartab, DiPac, Nutab Dextrose

12. 2. Binders and Adhesives: These materials are added either d r y o r in w e t - f orm t o f orm g r a n ul e s or t o f orm c o hes i v e c o m pa ct s f o r di r ect l y compressed tablet. Example: Acacia, tragacanth- Solution for 10-25% Conc. Cellulose derivatives- Methyl cellulose, Hydroxy p r o p y l m e t h y l c e llulo s e , H y d r o x y p r o p y l c e llulo s e Gelatin- 10-20% solution Glucose- 50% solution Polyvinylpyrrolidone (PVP)- 2% conc. Starch paste-10-20% solution Sodi u m a l g in a t e Sorbitol

13. 3. Disintegrants: Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in theGIT. E x ample: S t a r c h - 5 - 20 % of ta b let w e i g ht . Starch derivative – Primogel and Explotab(1-8%) C l a y s - V ee gu m H V , b e n t o n i t e 1 % l e v e l in c o l o r e d tablet only Cellulose C ellu l ose d er i v a t i v e s - A c - D i-Sol ( s od i u m ca r b o x y methyl cellulose) Alginate PVP (Polyvinylpyrrolidone), cross-linked

14. Superdisintegrants: Swells up to ten foldwithin 30 s e c on d s w h e n c ont a c t w a t e r . Example: cellulose, (p o l yme r), Crosscarmellose- cross-linked C r ossp o vi d o n e- c r oss-lin k ed p o vi d one Sodium starch glycolate- cross-linked s t a r c h . T h e s e c r o s s -l i n k e d p r o d u c t s s w e ll s with i n 3 s e c o n d s w h e n in c o n t a c t with w a t e r . A portion of d isi n t e g r ant is added granulation and a portion b e f o r e b e f o r e c o m p r e ss i o n , w hich se r v e as g li d an t s o r lubric a nt .

15. 4. Lubricant and Glidants: Lubricants are intended to prevent adhesion of the tablet materials to the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of the tablet granulation. Glidants are intended to promote f low of granules or powder material by reducing the friction between the particles. E x ampl e : Lub r ic a nt s - S t ear i c a cid , S t ea r i c acid salt - Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycols), Surfactants Glidants- Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as Cab-O- Sil, Syloid, Aerosil in 0.25-3% conc.

16. 5 . C olor i ng a g e nt : T h e us e of c o l o r s and d y e s i n a tabl e t h a s t h r e e pur p os e s: M asking of off c olo r dru gs Product Identification P r o d u c t io n of mo r e elegant p r o d u c t All coloring agents must be approved and certified by FDA. T w o f o r m s of c olo r s a r e u s ed in t a ble t p r e pa r a t io n – FD &C and D & C dyes. These dyes are applied as solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and employed as dry powder coloring. Example: FD & C yellow 6-sunset yellow,FD & C yellow 5- Tartrazine ,FD & C green 3- Fast Green,FD & C blue 1- Brilliant Blue ,FD & C blue 2 - Indigocarmine

17. F l av or in g a g e n t s : F o r c he w ab l e table t - flavor oil areused Sw ee t e nin g a g e n t s : F o r c he w ab l e ta b le t s: Sugar, mannitol. Saccharine (artificial): 500 time’s sweeterthan sucrose Disadvantage: Bitter aftertasteand carcinogenic Aspartam e (arti f icial) Disadvantage: Lack of stability in presenceof moisture.

18. L ac t ose N o n - r e a c t i v e i n a n h y d r o u s or h y d r o u s f orm H y d r o u s f orm u nd e r g o e s ma i l la r d r eact i on leading t o browning and discoloration of certain drugs, hence a n h y d r o u s f orm i s p r e f er r e d Bu t a n h y d r o u s f orm picks up mo i s t u r e w h e n e x posed t o humidity. In wet granulation, hydrous lactose of two varieties are used 60-80 mesh (coarse) and 80-100 mesh (regular) grade. L ac t ose f ormul a tio n sh o w g oo d r elease. L o w c os t diluent Bu t m a y d i s c olo r in p r e s e n c e o f amine dru g base s o r salts of alkaline compounds

19. S p ra y drie d lac t os e Lactose is placed in aqueous solution,removed impur i t i es and sp r a y dri ed M i x t u r e o f l a rg e alpha m ono h yd r a t e crystal s and sphe r i c al a gg r e g a t e s of smaller crystals Go o d flo w ability bu t less c omp r e ss i b i l i t y P oo r dilut i on potenti a l Less c omp r e ss i b i l i t y upo n ini t i a l c ompa c t io n Problem of browning due to contamination of 5- hydroxyfurfural which was accelerated in the presence of basic amine drugs and catalyzed by tartarate, citrate and a c e t a t e ions

20. F as t -F l o w la c t os e (e a r l y 19 7 s ) Sphe r i c al a gg r eg a t e s of mic r oc r y st a ls la c t os e monohydrate H e l d t o g e t h e r b y a hi g h e r c o n c e n t r a t io n o f g lass (amorp h o u s lac t ose) M u c h mo r e c om p r e ss i b l e H i g h l y f l ui d N o n h y g r o s c o p i c Tablets are three to four times harder than regular spray dried T a bl e t o se : a gg r om e r a t e f orm o f la c t os e M o r e c omp r e ss i b l e tha n sp r a y dri ed bu t less c omp r e ss i b l e tha n F as t Fl o la c t os e

21. St a r ch Ca n b e c o r n , w h e a t o r pota t o sou r c e USP g r a d e of s t a r c h has poor f l o w & c omp r e ss i o n characteristics Als o has hi g h mo i s t u r e c o n t e n t b e t w ee n b e t w ee n 11 & 14 %. Specia l l y dri ed s t a r c h e s also h a v e standa r d mo i s t u r e l e v e l of 2-4% Therefore used in wetgranulation

22. St a 1 5 00 : Intact sta r c h g r ain s a n d rup t u r e d sta r c h g r ain s that have been partially hydrolyzed and su b s e q ue n t l y a gg r ome r a t e d F r e e f l o w i n g , self lu b ric a t i n g , c o n t a inin g s l i g h t l y high MC (10 %) Due t o w hich d o es n o t f orm h a r d c o m pa c t s Dilution potential is minimal, not generally used as filler-binder but as fillerdisintegrant Retains the disintegrant properties of starch without increasing the fluidity and compressibility of the total formulation Fl o w p r omo t er s l i k e c ollo i da l s i l i c o n d i o x i d e i s needed. L u brica n t s t e n d t o d r ama t i cal l y sof t en table t s c o n t a inin g h i g h c o n c e n t r a ti o n s of S t a r c h 1 5

23. Dextrose 9 - 9 2 % d e x t r os e , 3 - 5 % m a l t os e and th e r ema inder hi g h e r g lu c os e po ly sa c c ha r id e s Available both anhydrous and a hydrateproduct E x c e ll e n t c om p r e ss i b i l it y a n d g oo d f l o w C o n t a i n 8 -10% mo i s t u r e and m a y i n c r e as e ha r dn e s s aftercompression L a r g e s t pa r ticl e size, t h e r e f o r e ble n din g p r o b l e m m a y occur Cerelose is alsoavilable

24. Cellulose Mic r oc r y sta l l i n e c e llulos e ( A vi c e l ) D e r i v e d f r o m a special g r a d e of pu r i f i ed alpha w oo d c e llulos e b y s e v e r e acid h y d r o ly s i s t o r e m o v e the amorphous cellulose portions, yielding particles c o n s i s t i n g of bu n dle s of n ee d l e l i k e mic r oc r y s t als P H 1 1 p o w d e r a n d P H 1 2 a r e th e t w o g r ades available. mos t c omp r e ss i b l e with Hi g hest dilutio n po t ential A s t r o n g c ompa c t f ormed du e t o s t r o n g h y d r o g e n bon d s ,a n d r up t u r e d du e t o passa g e o f w a t e r Ex t r e m e l y l o w c oef f ici e n t of fr i cti o n , n o lubricant N o t us e d as o n l y f ille r becaus e o f its c os t and density, use d in th e c on c o f 10 - 2 5 % a s a f ille r - binde r - disintegrant,

25. Tableting methods

26. Powders intended for compression into tabletsmust po s sess t w o essential pr o p e r ti es P o w d e r f l u i d i t y o r f l o w a bil i ty The material can be transported through the hopper into the die T o p r o d u c e table t s o f a c on s i s t en t w e i g h t P o w d e r f l ow ca n b e i m p ro v e d mec han i ca l l y b y th e us e of v i b r a t o r s , i n c o r po r a t e th e g lidant Powdercompressibility The property of forming a stable, intact compact mass when pressure is applied is called powdercompressibility E asi l y m i x e d w i th ot h e r pa r t i cl es H o m o g en o u s c olour i n g e t c F ri ct i o n a nd a dhe si o n p r ope r t i es

27. Sluggin g ( d r y granul a t i on ) : Blend is forced into dies of large capacitytablet p r e s s and c o m p a c t ed usi n g f l a t fa c e d p u n c h e s . c o m p a c t ed m a ss es a r e c al l ed sl u g s a n d p r o c e s s i s called slugging. S l u g s m i ll ed or s c r e e n e d t o p r o d u c e g oo d f r ee flowing granules for compression.

28. Dry compaction/Rollercompaction On a large scale compression granulation can also be performed on a rollercompactor. Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the ma t e r i a l at p r e ssu r e o f up t o 10 t o n s per linear inch . Materials of very low density require roller compaction to achieve a bulk density sufficient to allow encapsulation or compression. O n e o f the bes t e x amples o f th i s p r o c ess is the de n si f ica t io n of aluminum h y d r o x i d e . R oll e r c ompa c t o r is c apa b l e o f p r o d u c i n g as muc h as 500 kg/hr of compacted ribbon like materials which can be th en sc r eened and mille d in t o g r anules f o r c omp r e ss i o n .

29. Limitations of d r y granu l a t i o n D r y g r anulat i on of t e n p r o d u c e s a hi g h e r p e r c e n t a g e of fines or non compacted products, which could compromise the quality or create yield problems for the tablet. I t r e q u i r e s dr u g s o r e x c i p i en t s with c o hes i v e p r op e r t i e s .

30. W e t gra n ul a ti o n Th e mos t popular metho d ( o v e r 7 % ) G r anulat i on i s d o n e T o p r e v e n t se g r egation of th e c o n s t i t u e n t s of th e p o w d e r blend. To improve flowability of the powdermixture. T o i m p r o v e th e c ompa c t io n c ha r a c t e r i s t i c s of th e p o w d e r mixture due to better distribution of the binder within the granules. T o i m p r o v e homo g e n e i t y and thu s e n su r e c o n t e n t uniformity W e t g r anula t i o n is a p r o c e s s o f us i n g a solut i on bin d er t o the p o w d e r m i x t u r e . Th e am o un t of liquid ca n b e p r o p e r l y ma n a g e d ; o v e r w e t ti n g = t he g r anules t o b e t o o ha r d , u nd e r w e t t i n g = t o o soft and fr i ab l e. Aqueous solutions are safer than othersolvents.

31. P ro c ed u r e of W e t Granu l a t i o n S t e p 1 : W e i g h i n g a n d B l en d ing S t e p 2: w e t g r a n ula t e p r e pa r e d b y ad d in g th e bin d e r solut i on S t e p 3 : Sc r eening th e dam p mas s i n t o pellets or g r anules ( 6 - 8mesh) Step 4 : Drying the granulation in thermostaticallycontrolled ovens S t e p 5 : D r y sc r eenin g : Step 6 : Mixing with other ingredients: Adry lu b r i ca n t , antiad h e r e n t a n d g lida n t i s a d de d t o the g r anules ei the r b y dust i n g o v e r th e sp r ea d -out g r anules or b y ble n din g with th e g r a n ul e s . D r y b i nd e r , c olo r a n t or d i s i n t eg r a n t m a y b e also ad d ed in th i s s t e p . Step 7 : Tableting: Last step in which the tablet is fed into the di e c a v i t y and th e n c omp r e ss e d .

32. Li m i tat io n s of w e t granu l a t io n : M ul t ipl e s e pa r a t e s t e p s a r e i n v o l v e d . Not suitable for heat and moisture sensitive drugs Equipments Traditionally, dry mixing in wet granulation process has been carried out using, Sigma b l a d e mi x e r , H e a v y - d u t y p l an e ta r y mi x e r .

33. List of equipments used in granu l a t i o n H i g h S h ear g r an u l at i o n : i)Little ford Lodgiegranulator i i)L i t t le f o r d M G T g r a n ula t o r i i i )Diosna g r a n ula t o r iv)Gral mixer Granulator with drying facility: Flu i di z e d be d g r a n ula t o r D a y naut a m i x e r p r o c e sso r Dou b le c on e o r twi n shell p r o c e sso r T o p o g r a n ula t o r S p e c i a l g r an u l a t or : R o t o g r a n ula t o r Marumerizer

34. C om p r ession T ab l e t i n g p r o c e d u r e Filling Compression Ejection T abl e t c omp r es s io n ma c hi n e s Hopper for holding and feeding granulationto be compressed Dies tha t de f in e th e si z e and shape o f th e tablet Punches forcompressing the granulation within the dies Ca m t r a c k s f or gu i d i n g th e m o v e m e n t o f th e punches F ee d i n g mec h a n i s m s f or m o vi n g g r a n ula t i on f r o m the hopper i n t o th e dies

35. S in g l e punc h machine M u lt i - s t a t i on r ota r y p r e ss e s The head of the tablet machine that holds the upper punch e s , die s and l o w e r punc h es i n p la c e r o t a t e s As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of f ill i n g , c o m p r ess i o n and ejec t i o n. Th e p o rti o n s of th e head tha t hold th e up p er a n d l o w e r punches a r e calle d the uppe r and l o w e r t u r r e ts The portion holding the dies is called the die table

36. Compre s s i o n c y c l e G r anules f r o m hopper empty in th e f eed f r am e (A) c o n t a i n i n g s e v e r a l i n t e r c o nn e c t e d c ompa r t m e n t s . These compartments spread the granulation over a wide a r e a t o p r o v i d e t i m e f or th e die s (B) t o f il l . Th e pull d o w n ca m (C) gu i de s th e l o w e r punches t o the bottom, allowing the dies tooverfill Th e pun c hes the n pass o v e r a w ei g h t - c on t r o l cam (E), w h i c h r e d u c e s th e f i l l in th e die s t o th e d e s i r e d amount A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feedframe The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath th e upp e r c om p r e ss i o n r ol l (G)

37. The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and c ompa c t th e g r anula t i o n with i n th e dies Af t e r th e mo m ent of c omp r e ss i o n , th e upp e r punches a r e w i th d r a w n as th ey f oll o w th e uppe r punch r aisi n g ca m (H) Th e l o w e r punches r i d e up th e ca m (I) w h i c h bring s the tablet s f l u s h with o r sl i g h t l y a b o v e th e su r f a c e o f th e dies Th e tablet s s t r i k e a s w ee p off b la d e af f i x e d t o th e f r o n t of th e f eed f r am e (A) and slide d o w n a c hu t e i n t o a r e c e p t ac l e At th e same t i me , th e l o w e r pun c hes r e- e n t e r th e pull d o w n ca m (C) and th e c y c l e i s r e p e a t e d

38. Th e pr i n c ip l e mo d i f ica t io n f r o m ea r lier eq u i pm ent has been an increase in production rate which is regulated by N um b e r of t ool i n g se t s N um b e r of c omp r e ss i o n sta t i o ns R o t a ti on a l speed of th e p r e s s M ul t i r ota r y machine High speed r ota r y machine

39. P ro c e s s i n g p ro b l e m s Capping is the partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet. L amin a tion i s s e p a r a t i o n o f a tabl e t in t o t w o o r mo r e distinct layers. Both of these problems usually result from air entrapmentduring processing. Pi c kin g i s r em o v a l o f a t able t ’ s s u r f a c e ma t erial b y a punch. Sticking is adhesion of tablet material to a die wall. These two problems result from excessive moisture or substances with low melting temperatures in the formulation

40. M o t t l i n g is an unequa l c olo r dist r ib u t i on o n a tablet , with light or dark areas standing on otherwise uniform surface. Th i s r esults f r o m us e o f a dru g with a c olo r d i f f e r e n t f r o m tha t of th e table t e x c i p i en t s or f r o m a dru g wi t h c olo r e d deg r adati o n p r o d u c t s . Weight variation-granule size distribution,poor f i o w , pu nc h v ar i at i on H a r dn e s s v ar i ati o n Double impression-monograms or engraving onpunch

41. Reference The theory and practice of industrial pharmacy by Leon Lachman,A.lieberman

42. THANK YOU