T a b le t s a r e p r e p a r e d b y c o m p r e s s in g p u lv e r is e d a n d

g r a n u la t e d d r u g s in a ta b le t m a c h in e .

T h e te rm is d e r iv e d f r o m th e L a t in tabula =

tablet

A P P L IC A T IO N O F T A B L E T S• G e n e r a l ly ta b le t a r e c o n v e n ie n t ly s to r e d a n d t r a n s p o r t , s im p le to ta k e (p a r t ic u la r ly i f c o a te d ) a n d s ta b i l i t y is a lw a y s g o o d .

• I n r e s t r ic t e d s e n s e ta b le t a r e in t e n d e d fo r ta k in g in . T h e d r u g s s u b s t a n c e is a b s o r b f r o m th e g a s t r o in t e s t in a l t r a c t o r h a v in g a lo c a l e f f e c t o n i t .

• C e r t a in ta b le t a r e in t e n d e d to d is s o lv e o r d is in t e g r a t e s in th e m o u th to g iv e a lo c a l a c t io n , s u c h a s lo z e n g e s

• Effervescent tablet a r e in t e n d e d to f o rm a n a q u e o u s s o lu t io n (w it h th e d e v e lo p m e n t o f c a r b o n d io x id e )

• S o m e ta b s a r e t o b e s w a l lo w e d w h o le . T h e y c a n b e c o a te d to p a s s th e s t o m a c h u n c h a n g e d a n d d is in t e g r a t e in th e s m a l l in t e s t in e .(e n t e r ic c o a t e d ta b le t) o r fo rm u la t e d to g iv e a s lo w d r u g r e le a s e (d e p o t t a b le t s )

• F in a l ly th e r e a r e ta b le t s w h ic h a r e n o t in t e n d e d to b e ta k e n (e g . S o lu t io n ta b le t fo r p r e p a r a t io n o f r e a g e n t). W h e n a d r u g is in t e n d e d fo r im p la n ta t io n in t is s u e (im p la n ta t io n t a b le t s )

S k e t c h y a c c o u n t o f ta b le t p r o c e s s in g

I n ta b le t t in g p r o c e d u r e , i t is a lw a y s n e c e s s a r y t o u s e s o m e in e r t s u b s t a n c e s m ix e d w i t h th e d r u g a c t iv e in g r e d ie n t , t h e s e a r e th e Excipients. T h e s e e x c ip ie n t a r e o f th e fo l lo w in g m a in t y p e s :

• Diluents , m a k e u p th e s iz e o f th e ta b le t (a t le a s t 8 0 -1 0 0 m g )

• Binders g iv e ta b le t t h e m e c h a n ic a l s t r e n g th n e e d e d

• Glidants a r e n e e d e d s o th a t th e p o w d e r m ix t u r e f lo w f r e e ly th r o u g h th e fe e d h o p p e r .

• Lubricants & antiadhesives a r e u s e to r e d u c e th e f r ic t io n b e tw e e n th e ta b le t a n d th e d ie w a l l w h e n th e ta b le t e je c t e d a n d to r e d u c e a d h e s io n b e tw e e n th e ta b le t a n d th e p u n c h s u r f a c e s .

• Disintegrates g iv e th e ta b le t a r a p id d is in t e g r a t io n in w a te r .

• Flavoring agents a n a b le th e ta b le t t o b e ta k e n m o r e e a s i ly .

• Colouring agents c a n s im p l i f y th e id e n t i f ic a t io n o f ta b le t s

Diluents

• C o m m o n ly u s e d a r e ; la c t o s e , v a r io u s s ta r c h e s ,g lu c o s e , m a n n i t o l , c a lc iu m s u lp h a te (d e h y d r a te ), a n d m ic r o c r y s t a l l in e c e l lu lo s e .

• C h o ic e o f d i lu e n t d e p e n d in g o n th e t y p e o f th e ta b le t p r e p a r a t io n , s o lu t io n ta b le t s a n d e f f e r v e s c e n t ta b le t s s h o u ld g iv e a c le a r s o lu t io n o n d is s o lv in g . Im p la n t ta b le t u s u a l ly d o n o t c o n ta in d i lu e n t (u s u a l ly a r e D C ta b le t)

• T a b le t t in g p r o c e s s e s c a n in v o lv e th e u s e o f g r a n u le o r d ir e c t c o m p r e s s io n (D C ). D C ta b le t s a r e in c r e a s in g in p o p u la r i t y d u e to it s s h o r t e n in g o f p r o c e s s e s t im e . T o fa c i l i t a t e ta b le t t in g b y d ir e c t c o m p r e s s io n s e v e r a l f o rm o f d i lu e n t h a v e a r is e n , s u c h a s :

– sprayed dried lactose, n o w a r e c o m m o n ly u s e d

– mannitol is a ls o a v a i la b le in th e s p r a y e d d r ie d fo rm– calcium sulphate (dehydrate) a c t s a s b o th d i lu e n t a n d

d is in t e g r a t e

– microcrystalline cellulose h a s a r o u s e d th e g r e a t e s t in t e r e s t . P r e p a r a t io n is m a d e b y s p r a y d r y in g a f t e r t h e r e m o v a l o f a m o r p h o u s c e l lu lo s e b y a c id h y d r o ly s is . M ic r o c r y s t a l l in e C e l lu lo s e g iv e s ta b le t s h ig h m e c h a n ic a l s t r e n g t h a n d a t t h e s a m e t im e , r a p id d is in t e g r a t io n in w a te r .

B in d e r• E x a m p le o f b in d e r u s e in ta b le t s a r e g e la t in , s t a r c h , c e l lu lo s e e th e r , m ic r o c r y s t a l l in e c e l lu lo s e , s o d iu m a lg in a t e s , p o ly v id o n e , p o ly e t h y le n e g ly c o ls .

• I f t h e ta b le t t in g in v o lv e th e u s e o f w e t g r a n u la t io n , th e w e t g r a n u la t io n c a n b e c a r r ie d o u t w i t h th e fo l lo w in g :– G e la t in s o lu t io n (3 -5% ), f r e s h ly p r e p a r e d a n d w a rm a t 4 5°C.– S ta r c h m u c i la g e (1 0% ). P o ta t o s t a r c h is m ix e d w it h a n e q u a l

q u a n t i t y o f w a te r

– C M C m u c i la g e (3 % ). A s o lu t io n o d S o d iu m C a r b o x y m e th y k c e l lu lo s e .

W a te r la b i le d r u g s c a n b e g r a n u la t e d w i t h a n a lc o h o l ic s o lu t io n o f

c e r t a in b in d e r s u c h a s p o ly e t h le n e g ly c o ls , p o l iv id o n e a n d e th y l c e l lu lo s e

IF D C th e b in d e r is a d d e d a s s o l id in s t a t e o f s o lu t io n . M ic r o c r s t a l l in e c e l lu lo s e , v a r io u s c e l lu lo s e e t h e r s , p o ly v id o n e a n d p o ly e t h y le n e g ly c o l a r e u s e d fo r t h is p u r p o s e .

G l id a n t s

• E x a m p le o f g l id a n t s a r e : T a lc , s ta r c h , a e r o s i l , h ig h e r p o ly e t h y le n e g ly c o ls .

• T a lc h a v e b e e n th e g l id a n t e m p lo y e d m o s t f r e q u e n t ly , b u t i t s u s e d is d im in is h in g d u e to th e r is k o f i r r i t a n t e f f e c t .

• I t s h o u ld a ls o b e p o in te d o u t th a t f lo w a b i l i t y o f th e g r a n u le s is o f t e n a d e q u a te w i t h o u t th e g l id a n t .

L u b r ic a n t a n d A n t i-a d h e s iv e s

• E x a m p le s a r e : M a g . S te a r a te , s t e a r ic a c id , l iq u id p a r a f f in , s i l ic o n e m u ls io n , s o d iu m s te a r y l f u m a r a t e - m o s t c o m m o n ly u s e d is m a g . S te a r a t e .

• T h is s u b s ta n c e is d e c id e d ly h y d r o p h o b ic a n d th e r e f o r e p r o lo n g s th e d is in t e g r a t io n a n d th e d is s o lu t io n o f a ta b le t . T h e a d d i t io n s h o u ld th e r e f o r e b e s m a l l a s p o s s ib le (u s u a l ly 0 .2 % )

D is in t e g r a n t

• E x a m p le o f d is in t e g r a n t a r e s ta r c h e s o f v a r io u s k in d ,a lg in ic a c id , A e r o s i l , m ic r o c r y s t a l l in e c e l lu lo s e , s u r f a c e -a c t iv e a g e n t s , s o d iu m b ic a r b o n a te , c a lc iu m c a r b o n a te .

• S ta r c h a r e c o m m o n ly u s e b e fo r e g r a n u la t io n o r a d d i t io n to d r y g r a n u le s . T h e ta b le t d is in t e g r a t e s in w a te r d u e to th e s w e l l in g o f th e s ta r c h g r a in s

• B y a d d i t io n o f s u r f a c e -a c t iv e a g e n t s h y d r o p h i l iz a t io n is o b ta in e d , w h ic h w i l l im p r o v e th e d is in t e g r a t io n o f th e ta b le t

• E f f e r v e s c e n t ta b le t d is in t e g r a t e d u e to th e l ib e r a t io n o f c a r b o n d io x id e f r o m th e c i t r ic a c id a n d s o d iu m b ic a r b o n a te in c lu d e d in th e ta b le t .

• C e r t a in ta b le t s a r e in te n d e d to d is s o lv e s lo w ly in th e m o u th (s u c k ta b le t s ) T h e y c o n ta in s u g a r , a c a s ia , e t c . a n d a r e c o m p r e s s u n d e r h ig h p r e s s u r e to g e t a s lo w d is in t e g r a t io n .

M E T H O D O F T A B . P R E P A R A T IO N1 . M ix in g

T h e p r e p a r a t io n o f a ta b le t is c h a r a c te r is e d b y a n u m b e r o f m ix in g o p e r a t io n s a s fo l lo w s :

• t h e d r u g is m ix e d w i t h d i lu e n t s a n d o th e r e x c ip ie n t s ,

• t h e g r a n u la t io n f lu id is a d d e d ,

• t h e d r ie d g r a n u le s a r e m ix e d w i t h lu b r ic a n t

M ix in g p r o c e s s e s m u s t b e c a r r ie d o u t w i t h th e p a r t ic u la r c a r e e s p e c ia l ly w h e n th e d r u g c o n te n t o f e a c h ta b le t is s m a l l .

T h e m e th o d o f a d d in g d r u g in th e g r a n u la t in g s o lu t io n is u s u a l ly a d v is a b le b u t n o t a lw a y s p o s s ib le .

A d m ix tu r e o f th e lu b r ic a n t m u s t b e m a d e in g e n t le w a y s o a s n o t to b r e a k u p th e g r a n u le s .

2 . W e t G r a n u la t io n• T h e c o m m o n e s t m e th o d o f p r e p a r in g g r a n u le s .

• T h e m ix t u r e c o n s is t in g o f d r u g , d i lu e n t , e t c ., is m o is t e n e d w i t h a s u f f ic ie n t q u a n t i t y o f a g r a n u la t in g f lu id (e g ., 4 % g e la t in s o ln ) s o th a t w h e n p r e s s e d g e n t ly th r o u g h a s ie v e , i t w i l l a c q u ir e a g r a n u la r s t r u c t u r e ( u s u a l ly a m e s h o f 0 .7 m m fo r s m a l l t a b le t s a n d a c o a r s e r s ie v e , 0 .7 -1 .0 is n e e d e d fo r la r g e r ta b le t).

• T h e m o is t g r a n u le a r e th e n d r ie d a t a m o d e r a te te m p e r a tu r e (3 0 -4 0°C) in a d r y in g o v e n , n o t , h o w e v e r to a c o m p le t e d r y n e s s . T h e g r a n u le s m u s t s t i l l c o n ta in a c e r t a in a m o u n t o f m o is t u r e . I f th e m a s s is to o d r y th e r e a d y ta b le t w i l l s u f f e r “c a p p in g ”

• A f t e r d r y in g th e c a p a r e a g a in s ie v e b u t w i t h a c o a r s e r s ie v e s o th a t th e a g g lo m e r a te d g r a n u le s a r e s e p a r a te d .

• T h e lu b r ic a n t is th e n a d d e d a n d i f n e c e s s a r y th e d is in t e g r a n t a n d /o r e t c ., a n d a f t e r th is th e g r a n u le a r e r e a d y fo r ta b le t t in g

• T h e g r a n u le s p r e p a r e d c o n ta in v a r io u s s iz e s a s w e l l a s a q u a n t i t y o f r a th e r f in e p o w d e r . S u c h n o n -u n i f o rm g r a n u le s a r e m o s t s u i t a b le .

3 . D r y G r a n u la t io nT h is p r o c e s s in v o lv e d p r e c o m p r e s s io n , d o u b le

c o m p r e s s io n , s lu g g in g .

• T h e m ix t u r e o f d r u g s a n d e x c ip ie n t a r e c o m p r e s s e d d ir e c t ly in t o la r g e ta b le t o r “s lu g s ”(u s in g m a c h in e w i t h s p e c ia l c o m p a c t in g e q u ip m e n tm e n t , w h e r e th e m ix t u r e is fo r c e b e tw e e n r o l le r s )

• T h e s lu g a r e th e n b r o k e n -d o w n a n d s ie v e d

• A d d in g o f lu b r ic a n t

• T h is m e th o d o f f e r c e r t a in a d v a n ta g e s o f w o r k e c o n o m y a n d fo r p r e p a r a t io n o f h y g r o s c o p ic ta b le t s .

• H o w e v e r th e c o m p a c t in g o f t e n r e s u l t in s lo w d is in t e g r a t io n o f a ta b le t a n d a lo w d is s o lu t io n r a t e .

4 . P a r t ia l G r a n u la t io n• W a te r la b i le d r u g s , w h ic h c a n n o t b e s u b je c t e d to

w e t g r a n u la t io n , a r e o f t e n t r e a te d in th is w a y

• T h e d r u g s in g r e d ie n t in th e fo rm o f f in e p o w d e r is m ix e d w i t h p r e v io u s ly p r e p a r e d , in e r t g r a n u le s a n d a s u f f ic ie n t q u a n t i t y o f lu b r ic a n t .

• P r o b le m o f m ix in g w i l l b e p a r t ic u la r ly c r i t ic a l w h e n o n e o f th e c o m p o n e n t s is in th e fo rm o f g r a n u le s a n d th e d r u g q u a n t i t y is s m a l l .

• T h e te n d e n c y o f s e g r e g a t io n w h ic h c a n o c c u r d u r in g h a n d l in g o f th e f in is h m ix tu r e , p a r t ic u la r ly in th e fe e d h o o p e r o f th e ta b le t m a c h in e , m u s t b e w a t c h c a r e f u l ly .

5 . G r a n u la t io n in f lu id iz e d b e d

• W e t g r a n u le in a f lu id iz e d b e d d r y e r is n o w v e r y c o m m o n

• W ith th e a id o f th is e q u ip m e n t i t is p o s s ib le to c o m b in e a s e r ie s o f w o r k in g s te p s a n d c o m p le t e th e w h o le p r o c e s s in a s h o r t t im e

• M ix in g , G r a n u la t io n (w h e r e g r a n u la t io n f lu id is s p r a y e d w h i le m ix in g ), a n d d r y in g , a l l ta k e p la c e in a c lo s e s y s te m

• T h is p r o c e s s r e q u i r e d a th o r o u g h p r e p a r a t o r y s tu d y in o r d e r to h a v e g o o d c o n t r o l o f o u tp u t

N o te : S p r a y d r y in g is u s e d to s o m e e x te n t fo r p r e l im in a r y t r e a tm e n t in ta b le t t in g . A s u s p e n s io n o f th e d r u g s u b s t a n c e , d i lu e n t , e t c ., is s o m e t im e s t r e a t e d in th is w a y . T h is m e th o d c a n g iv e th e fa v o r a b le p r o p e r t ie s g r a n u le s fo r ta b le t t in g .

5 . D ir e c t C o m p r e s s io n (D C )

T h is p r o d u c t io n m e th o d w a s fo rm a l ly o n ly u s e d fo r a fe w d r u g s (e g ., a c e th y l s a l ic y l ic a c id ). H o w e v e r , b e c a u s e o f o b v io u s a d v a n ta g e s c o n s id e r a b le e f f o r t h a v e b e e n d e v o te d to d e v e lo p th is te c h n iq u e .

I t w a s fo u n d th a t m a n y s u b s ta n c e s c a n b e c o m p r e s s e d d ir e c t ly , i f a n e f f ic ie n t f o r c e fe e d f lo w is u s e d in th e ta b le t t in g m a c h in e a n d s p e c ia l e x c ip ie n t a r e in t r o d u c e d w h ic h fa c i l i t a t e th e u s e o f d i r e c t c o m p r e s s io n

G r a n u le s s h o u ld c o m p ly w i t h t h e fo l lo w in g g e n e r a l r e q u i r e m e n t

• G r a n u le s fo r m ix t u r e m u s t d is s o lv e e a s i ly

• g r a n u le s fo r d ir e c t in t a k e m u s t d is in t e g r a te

in w a te r a t 3 7 °C w it h in a r e a s o n a b le t im e ,

• e n te r ic c o a te d g r a n u le s m u s t c o m p ly w i t h th e te s t o f a c id r e s is t a n c e a n d o f d is in t e g r a t io n in s t im u la t e d in t e s t in a l f lu id ,

• g r a n u le s s h o u ld h a v e s u f f ic ie n t m e c h a n ic a l s t r e n g th

T e c h n ic a l E q u ip m e n t1 . P r e p a r a t iv e t r e a tm e n t

• T h e in i t ia l m ix in g o f t h e p o w d e r s is o f t e n c a r r ie d o u t in a ribbon mixer o r a double-cone mixer

• In wet granulation, the binding fluid is worked into the mass with a dough mixer or a planetary mixer. The moist mass is pressed through the screen in an oscillating granulator. The lubricant is added with the aid of a further double cone mixer

• Other large scale procedure have also been developed for wet granulation: the use of fluidized bed dryer is very common

• W e t g r a n u la t io n c a n a ls o b e s im p l i f ie d in o t h e r w a y s . E g ., t h e Diosna mixer, a c lo s e in t e n s iv e m ix e r w h e r e t h e g r a n u la t in g f lu id is a d d e d th r o u g h a s p e c ia l p o r t a n d is m ix e d in , th e r e a f t e r h o t a ir is b lo w n in t h r o u g h a s l i t s in t h e b o t t o m o f th e m ix e r . A f i l t e r b a g is c o n n e c t e d o n to p o f t h e m ix e r . A f t e r d r y in g , t h e lu b r ic a n t is a d d e d w h e r e u p o n th e g r a n u le a r e r e a d y fo r c o m p r e s s io n

• F o r ta b le t t in g b y s lu g g in g , s p e c ia l c o m p a c t in g m a c h in e a r e u s e d (e g ., t h e Chilsonator, t h e Hutt c o m p a c t o r .

2 . T h e T a b le t t in g M a c h in e

F o r s m a l l s c a le p r o d u c t io n , th e S ingle -Punch Machine is still in use. Large industrial production is nearly always carried out with the aid of Rotary Tablet Machines.

S ingle-punch Machine as a concept

• A s in g le -p u n c h m a c h in e h a s a stationary die a n d a movable hopper

• C o m p r e s s io n ta k e s p la c e in th e d ie b e tw e e n th e u p p e r a n d th e lo w e r p u n c h e s .

• T h e m o v e m e n t o f th e p u n c h e s , a n d a ls o th e h o p p e r s h o e , a r e g u id e d b y th e m a in s h a f t o f th e m a c h in e w i t h th e a id o f e c c e n t r ic s .

• T h e lo w e s t p o in t o f th e lo w e r p u n c h (th e lo w e r s c r e w ) n e e d to b e a d ju s t e d s o th a t th e d ie w i l l h o ld th e q u a n t i t y g r a n u le s e q u a l to th e in t e n d e d w e ig h t o f th e ta b le t .

• T h e u p p e r p u n c h is p u t in i t s p la c e a n d th e e c c e n t r ic is a d ju s t e d to e n a b le th e u p p e r p u n c h to e x e r t s u f f ic ie n t p r e s s u r e to e n s u r e th e ta b le t to h a v e g o o d h a r n e e s d is in t e g r a t io n p r o p e r t ie s

What did I learn?

R e c a p S e s s io n

G r a n u la t io n

• D ir e c t C o m p r e s s io n

• W e t G r a n u la t in g

• D r y G r a n u la t in g

W h y G r a n u la t e

• T o im p r o v e p o w d e r f lo w .

• T o im p r o v e c o m p r e s s ib i l i t y .

• T o r e d u c e f in e s .

• T o c o n t r o l t h e te n d e n c y o f p o w d e r s to s e g r e g a te .

• T o c o n t r o l d e n s i t y .

• T o c a p tu r e a n d fu s e s m a l l q u a n t i t ie s o f a c t iv e m a te r ia l.

W h y ? W h y ? W h y ?

▪ G o o d W e ig h t C o n t r o l

▪ G o o d T h ic k n e s s C o n t r o l

▪ G o o d H a r d n e s s C o n t r o l

▪ G o o d E je c t io n

▪ N o C a p p in g

▪ N o L a m in a t io n ▪ N o S t ic k in g ▪ G o o d F r ia b i l i t y ▪ G o o d D is in t e g r a t io n ▪ G o o d D is s o lu t io n