75P E F F E C T OF S L U G G I N G PRESSURE ON THE P R O P E R T I E S OF GRANULES AND TABLETS PREPARED FROM POTASSIUM PHENETHICILLIN P. Musikabhumma' and K.A. Khan, Beechm Pharmaceutical - Research D i v i s i o n , Clarendon Road, Worthing, Sussex. Slugging is one of t h e o l d e s t and most widely used processes f o r t a b l e t t i n g high dose moisture s e n s i t i v e drugs. Although both w e t granulation and direct compression are well researched, t h e slugging process has received l i t t l e 01: no a t t e n t i o n . The r o l e of pre-compression and subsequent s i z e reduction, t o improve compaction of poorly compressible drugs, i s not Yet c l e a r l y understood.

The object o f t h i s i n v e s t i g a t i o n w a s t o examine t h e e f f e c t of c e r t a i n proc e s s i n g f a c t o r s on t h e p r o p e r t i e s of granules and t a b l e t s produced by slugging a high dose, moisture s e n s i t i v e p e n i c i l l i n : potassium p h e n e t h i c i l l i n ( B m x i l ) . The slugging pressure was optimised by m a k i n g s l u g s at various pressures, using both s i n g l e and double slugging systems. The slugs were then reduced t o granules u s i n g an Apex comminuting m i l l and t h e e f f e c t o f both hammers and m v e s forward on granule and t a b l e t p r o p e r t i e s was examined. The following granule p r o p e r t i e s were studied: bulk and tapped density, f r i a b i l i t y , p a r t i c l e s i z e d i s t r i b u t i o n and t r u e density. The granules were t a b l e t t e d at f o u r pressures, each t a b l e t containing 125mg of p h e n e t h i c i l l i n and t h e following t a b l e t p r o p e r t i e s were studied: weight v a r i a t i o n , p o r o s i t y , d i s i n t e g r a t i o n time, d i s s o l u t i o n time, crushing s t r e n g t h and f r i a b i l i t y . The surface a r e a and scanning e l e c t r o n micrographs of some s e l e c t e d granules and t a b l e t s were a l s o examined. The r e p r o d u c i b i l i t y of results u s i n g two batches of potassium p h e n e t h i c i l l i n was a l s o compared. The r e s u l t s showed t h a t granules obtained from slugs made had b e t t e r compressibility than those obtained from slugs pressure. The e f f e c t f o r example of slugging pressure on strength/pressure p r o f i l e s of t a b l e t s i n a s i n g l e slugged i n Figure 1.

at lower pressure made a t higher t h e crushing system, i s shown

Fig. 1 ; E f f e c t of t a b l e t t i n g pressures on t h e crushing s t r e n g t h s of potassium p h e n e t h i c i l l i n t a b l e t s prepared from a formulation, s i n g l e slugged a t f o u r pressures (Apex milled, hammers forward)

A similar r e l a t i o n s h i p w a s observed f o r double slugged granules. The granules obtained from slugs compacted a t lower pressure were more porous and f r i a b l e than those obtained from slugs compacted at higher pressures. It i s suggested t h a t t h e former yielded t o a g r e a t e r degree on t a b l e t t i n g , producing stronger p a r t i c l e t o p a r t i c l e bonds, which r e s u l t e d i n t a b l e t s of higher crushing strengths. The study demonstrated t h e importance of optimising slugging conditions f o r producing t a b l e t s of desirable properties.

'School of Pharmacy, Liverpool Polytechnic, Byrom S t r e e t , Liverpool.