H l X I n 6 ACTION AND EVALUATION OF TABLET LUBRICANTS I N

DIRECT CWRESSIOW
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C.K. Bolhuis. C.F. Lerk and P. B r o c r w

Laboratory for Phamacaut ical Technology

University of Groningan

Antonius Deusingiaan 2 .
9713 AW Groningen, The Matherlands
For personal use only.

ABSTRACT

Th. effect of a series of d a r n lubricants during mixing on

both lubricating action and binding properties of a direct compres-

sible tablet formulation has bean investigated and compared with

the effect of magnesium s t e a r a t e . Lubricants which gave the best

lubricating action (magnesium s t e a r a t e , hydrogenated vegetable oi 1s

and glycerides) caused the largest reduction in tablet strength

with an increase in.mixing time. When used in concentrations of

It. the hydrogenated vegetable o i l s and glycerides tested gave

about the s a n e reduction of the ejection force as 0 . 5 2 magnesiun

stearate, but their effect on tablet hardness during mixing was

Chpyryht 0 1980 by Mu
d Dakar. lac.
 16 EOOW1UIS. LERK, AND BROERSHA

m c h smaller. This result was c o n f l m d for three direct cocapresslble

tablet formulations, carposed wlth different exclpients, where mag-

nesium stearate c w l d be replaced a d v m t a g m s l y by Bocson VP o r

5 terotcx.
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I)(fROIWCTION

In the production o f tablets, lubrlcanta are u s u a l l y added to

reduce the friction between tablet matcrlal and the die wal dur "9

compression and ejection of the tablet. Higuchi and co-workers

For personal use only.

(1-3) evaluated various moterials as tablet lubricant and found

that salts of fatty acids were b e s t (3). Of those, nagnesiun stearate

i s perhaps the most widely used pharmaceutical lubricant. I t i s w e l l

known, however, that magnesium stearate can have a strong negative

e f f e c t on both binding and disintegration properties o f tablets and

consequently on drug release and even in soam cases -c.q.in aspirin

tabicts- on the drug stabll ty. For this reason several new lubr cants

have been Introduced in the last 10-15 y e a r s . Alpar (4) reported the
succetful use o f polytetraf uorosthylene as a tablet lubricant. he

r e s u l t s shomd' I t to be as equally effectlve as magnesium stearate

when used In crmcentrationr o f 1 par cent, i t did mot, howaver, ma-

terlaily affect the dislntegratlm tlme and the strength o f the lac-

tose tablets studied. Further work ( 5 . 6 ) with aspirin sucrose and

hexaaine confirmed these properties. Hydrogenated vegetable 0 1 1 s

such as hydrogenated cotton seed 01 I ( S t e r o t e x q and hydrogenated

castor oil (tutlna%) can be used as tablet lubricants. Sterotex

 TABLFI' LUBPIclwfs I7

Is c l a i r d t o be e f f e c t i v e i n concentrations of 0.2 - 1% for g r m u -

I a t i o n s and 1.5 - 3% for powdar a i x t u r e s w i t h o u t influencing disinte-

g r a t i m t i r and t a b l e t hardness (7). b r l - and Shmgraw ( 8 ) .

however, found only s l i g h t d i f f e r e n c e s i n the d i s s o l u t i m r a t e o f

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s o d l u s a l i c y l a t m frrm t a b l e t s , when 12 ugnesiu stmarate ws re-

placed by the s a m concentration o f Sterotex. S i a i i a r e s u l t s were

found f o r a s p i r i n t a b l e t s ( 9 ) . Sterotex has, however, a favourab I t

effect on the s t a b i l i t y o f a s p i r i n t a b l e t s ( 1 0 ) . Cutina HR i s claimed

to be e f f e c t i v e I n concentrations b e t m e n 0 . 3 and 2.0% 11).

Another group o f d r n l u b r i c a n t s i s forwd by ( a i x t u r e s o f )

glycerides. J r i n o t and Had. (12) Introduced a g l y c e r y l p a l o i t o -

For personal use only.

stearate, marketed as Prdcirol? 1he.product Is claimed t o have both

b i n d i n g and l u b r i c a t i n g p r o p e r t i e s s i u l t M . o U s l y , when used i n

concentrations o f 1-52 I t uas found t h a t r e p l a c u n t o f u g n e s i u a

stmarate by Prdclrol cocrtributed considerably t o th. Irprovemnc o f

a n u h e r o f properties o f tablets ( 1 3 , 14). A less w e l l knoun a i x t u r e

o f glycerides, which can be used as t a b l e t l u b r i c a n t i s Bocson$P

( I S ) . I t i s e f f e c t i v e i n concentrations of 0.4 - 3% and i s claimed

not t o have a negative e f f e c t on t a b l e t hardness.

I n several studies, comparative a v a l w t l o n s b a t w e n w g n e s l u a

s t e a r a t e and aodarn l u b r i c a n t s such as p o l y t e t r a f l w r o c t h y l c n e (P.T.F.E.),

hydrogenated vegetable 0 1 Is and g l y c e r i d e s were c a r r i e d out. P a r i s (16)

compared various concentrations of u g n e s i u a stearate, P r d c i r o l ,

Cutina HR and P.T.F.E. i n g r a n u l a t l o n s as well as i n d i r e c t campressiblt

t a b l e t mixtures. The author found that the l u b r i c a t i n g e f f e c t and

the Influence on t a b l e t hardness were dependent on the nature and

 18 BOURILS, IXRK, AND BROERSHA

the cok-.entration o f the lubricant and thc foraulatlon in which I t

uas used. The best lubrlcatlng properties were obtained with 0.58

llsgnariu stearate, It Pr4cirol or 0.5 - 1% P.T.F.E. C U t i M HR gave

less utfsfactory results. Magnesiu stearate and PrilcIroI c a w e d ,

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however, a stranger decremre In tablet crushing strength than the

other lubricants. Delattre et al ( 1 7 ) evaluated different lubricants

in a direct coapressibie tablet formulation containing extra fine

crystalline lactose (lactose E.F.C.) and aicrocrystaI1iM cel luiose

(Avice&H 101). As both tabletting chracberistics (lubricating

coefficient, ejection force) and mechanical tablet properties

For personal use only.

(crushing strength) were strongly influenced by both the nature and the

percentage of the lubricant, for each lubricant the minimum effective

concentration w s determined. The best overall propertles f w n d for

Pr4cirol and stearic a c i d -re i n concentrations of 1% and

p o g n e s i u stearate In a c w e n t r a t l o n of 0.25%. Increase in lubrl-

cant concentration w a s , however, more crltlcal when magnesiun ste-

arate was used. Due to the hydrophlllc nature of the tablet exclpient!

used, there was almost no difference In the effect o f the lubricants

on the disintegration tlw of the tablets. Stacn et a1 ( 1 8 ) com-

pared the properties of magnerlu stearate with various other lu-

bricants under uhlch giycerldas, hydrogenated vegetable oils and

P.T.F.E., using lactose E.F.C. IS tablet exclpient. The results of

the effect o f the lubricants on both lubrication and tablet proper-

t i e s s h o w d that 0.25% n u q n e r l u stearate can often be replaced

advantaaeously by for instance 4% Ste-otex, 2-4% PrCclrol or 44, P . T . F . E .

 TABLET LUBPICANTS 19

kn a l l of the studies aentioned above, the i n f l u e n c e of the

N i x i n g time of l u b r i c a n t s and e x c i p i e n t s un the e f f e c t o f lubri-

c+ts on' both lubrlutim and t a b l e t ' p r o p e r t i a s m s not taken i n t o

account. I n previous work from our laboratory (19) it uas found

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that the decraase of b i n d i n g forces of d i r e c t ccmmpresrible e x c i p ents

i s not m l y dependent m the c o n c e n t r a t i o n o f magnesium s t e a r a t e

but .\so e s p e c i a l l y on the i n t e n s i t y o f the m i x i n g procedure. The

phenoarnon u a s e l u c i d a t e d by tha formation o f a l u b r i c a n t film upon

the substrate surface o f w g n e s i u stearate moiecuias, which are

sheared o f f frm the u g n e r i u s t e a r a c t crystals d u r i n g the m i x i n g

For personal use only.

process. Studies w i t h r t e a r i c acld and metal r o l p s of s t e a r l c a c i d

shoued that film f o r m t i o n Is not only e x h i b i t e d b y n a g n e s l w rtaa-

r a t e : a l l the l u b r i c a n t s decraased the crushing s t r e n g t h of t a b l e t s

f r o a d i r e c t c a r p r e s s i b l e s t a r c h ( S T A - S 1500) w i t h an increase i n

m i x i n g time of the blends ( 2 0 ) . The r e s u l t s shoued, i n a d d i t i o n

that the e f f e c t was dependent on both the nature and par i c l o siza

o f the l u b r i c a n t . On the o t h e r b n d , the b i n d i n g between the

p a r t i c l e s was not a f f e c t e d by P.T.F.E. because t h i s i u b r cant has

M laminar s t r u c t u r e and w i l l n o t form P l u b r i c a n t f i l m d u r i n g

the m i x i n g process.

The o b j e c t o f t h i s study i s the i n v e s t i g a t i o n o f the eFfect o f

a s e r i e s o f modern l u b r i c a n t s such as hydrogenated vegetable oils

and g l y c e r i d e s d u r i n g n i x i n g on both l u b r i c a t i n g a c t i o n and b i n d i n g

p r o p e r t i e s of d i r e c t compressible tablet formulations. The r e s u l t s

 m WLHUIS. W,AND BROERSHA

will be compared with the effect o f u g n e s i u stearate, in order

to facilitate the choice o f a proper lubricant in direct compression.

EXP€RlHEHTAL
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siac!g!r : The direct compressible excipients used were: micro-

crystalline cellulose N . F . (Avicel PH I01 and P H 102)', microfine

3
cellulose (Elcema@t 2 5 0 ) 2 , direct compressible starch (STA-Rx IS00 ) ,
-lose ,'V d i c a l c i u phosphate dlhydrrta ( E m c o a p r e s s q S and extra

Fine crystalline lactose (Lactose E . F . C . ) ' . The lubricants used

7
graphite ,
For personal use only.

were: magnesium starrate Ph.Med. V l ' , talc Ph.kd. Vi',

8 9
stearic acid (phamrceutleal qua1 I ty) , p l y t e t r a f luorocthylene ,

PrCci rol-Ato-S1', Sterotex'', beson VPf2, Cutina HRf3 and I-leucine

1s
99%''. The drugs used were: prednisone Ph.Ned. VI I , micronized ,
7
phenobarbi tone Ph.Eur." and paracetam1 Ph.Hcd. V I I

Particle densities were determined with an air canparison p y c n m t e r 17

The specific surface by weight o f the lubricants was determined

by nitrogen adsorption
18
.
Hixlng of ths blends of excipients with different lubricants was

p e r f o m d in r Turbula mixer" at 90 rpm. for the placebo tablets

and in a I-litra cubic tunbllng mixer a t 60 rpm. for the prednisone.

phenobarbitone and yaracetaml tablets. F o r both methods, the loading

wds about 20%. & f o r e blendlng the lubricants were sieved through a

I50 j n sieve.
 TAB= LIJBPICIMS 21

I f not s t a t e d otherwise, it* blends -re c w r e r s e d t o f l a t tablets

using an i n s t r u u n t e d s i n Q l e punch machine at a machine speed of

18 c y c l r s / r i n . The Instru*ntatlon o f the machine ha5 been

reportod p r o v i o u s i y by Croennoid et a1 (21).

-
Tablet d i a a e t e r and
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t a b l o t weight -re 9 I and

I 300 mg for the placebo t a b l e t s , 9

and 200 mg for tha prodnisone and p h o m A w r b i t w tablets and 13 m

and 715 mg f o r tha p a r a c e t m o l t a b l e t s , r e s p e c t i v e l y . The corpresslon

force used w s 20 kW. The data for the rjection force represent the mean

of at l u s t ten coapressions.
i n a p r e l i m i n a r y test, placebo tablets were prepared by i n t r o -

ducing manually a waigtwd quantity o f 300 mg o f the blend i n f o a

For personal use only.

prelubrluted 9 111 d i e o f a c4.presslon device, mounted b o t w a n the

p l a t t e n s o f an Instrumenrod h y d r a u l i c press. Tha samples yare

compressed at a c 4 q r e r s i o n force of 20 kN with a loading r a t e o f

2 kWs.

The crushing s t r a n g t h o f tha c w p s c t s w s measured i ~ d i a f s l y

a f t e r c o q w e s r i o n using a r o t o r i z e d H e b e r l r i n i n s t r u n t . The data

given are the m a n o f a t l e a s t ten t a b l e t s . The f r i a b i l i t y o f the

t a b l e t s war determined i n a Rachc f r l a b i l a t o r . Samples of 10 t a b l e t s

were weighed, subjected to r o t a t i o n for 5 a i n u t e r at 20 rpa. and then

reuml9h.d a f t e r careful dusting. The percentage of t a b l e t m i g h t loss

was then calculated. The d i s i n t e g r a t i o n time of the t a b l e t s war d e t e r -

mined using the USP X I X apprratur. The data given a r e the maan o f

the d i s l n t e g r a t i o n time o f 6 i n d i v i d u a l t a b l a t s .
 22 DOUIUIS, LEBK. AND BROERSHA

RESULTS M D DISCUSSION

In order to study the nixing action of different lubricants on

both ejection force dur ng compression and tablet crushing strength.

a p l a c e b o mixture wi hwt lubricant containing 502 lactose E.F.C.,

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25% STA-Rr I500 and 252 Elcana C 250 was prepared, f r a which tab-

lets wlth sufficient crushing strength and ejection force could

be compressed. As i t was not possible t o prepare tablets with

same o f the lubricants studied, using the eccentric press, the

effect o f mixing with lubricants on tablet hardness was studied

in a preliainary test, using an instrumented hydraulic p r e s s and a

For personal use only.

loose, prelubricated die (f igure I ) .

Iigure 1 .
Xffoct of mixing tiw on t h o cruahing atroogth 02 tablets corprom-
a d I- blood. Of 5- lacto.. X.F.C.. 251 S T A - h ls00 and 15% Llco.a
0 150 with 1.0% of ratiouo lubricant..
 TABLET LUBRICANTS 23

Figure 1 shows the effect of mixing time ( l o g . scale) on the

crushing strength o f tablets, coatpressed from blends of the placebo

mixture with 1.0% of various lubricants. The specific surface by

w i g h t o f the tubrlunts used is given in table 1. The figure showr

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that graphite, talc and polytetraflwroethylene (P.T.F.E.)

had little or no effect on the crushing strength of the tablets.

As could be expected from previous work (IS), a strong dacraase

in crushing strength was found with magnesium stearate as tablet

lubricant. Although the modern lubricants I-lcuclne, Cutiru HR,

Starotex, baron VP and PrCcirol gave a strong decrease in-crushing

For personal use only.

s t r e q t h o f the tablets with on increase in mixing ti-, the effect

was l e s s than the effect o f magnesium stearate: after 2 minutes

rixing the crushing strength decreased with about 10 kg for tablets wit

TABU I

Bpocliic auriace by w i g h t of tho lubrlcanta u a d .

2
Boemn VP 1.0 I /I
2
Cutina M 1.2 I /g
2
graph1t o 6.4 I /g
2
1-lowine 1.8 I /g

u g n o a i ~ matoarate 1 4 . 3 mA/g
2
p o l ~ t o t r a i l w r o ~ t b y l ~ a o2 . 0 I /g
2
Prkirol 1.6 I /g
2
aterotox 1 . 6 I /g
2
3.3 I /g
 24 BOLJNLS. LEBL(, AND BROERSMA

s r g n e s i m s t e a r a t e but w i t h not more than about 5 kg f o r t a b l e t s

w i t h I - l e u c i n e , Cutina HR, Sterotex, Boeson VP or P r i c i r o l as

l u b r i c a n t . I t should. hocsver, be noted t h a t the decrease-rate

w s f w n d t o be dependent on the p a r t i c l e s i t e o f the l u b r i c a n t (20)

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so t h a t the rank-order fwnd r e f e r s o n l y t o the l u b r i c a n t s used.

Seann i ng e l e c t r o n micrographs have shown that a l l the l u b r l -

cants t e s t e d except P.T.F.E..have a laminar s t r u c t u r e . T h i s

suggests tha the l u b r l c a n t s which g i v e a decrease i n c r u s h i n g

strength dur ng the n i x i n g process a r e sheared o f f and f o r m

a l u b r i c a n t b a r r i e r on the e x c i p l e n t p a r t i c l e s , nterfcring w th
For personal use only.

the binding, j u s t as p r e v i o u s l y found f o r magnes u n s t e a r a t e

(19, 20, 2 2 ) . P.T.F.E. has no laminar s t r u c t u r e and w i l l n o t

fora a l u b r i c a n t f i l m d u r i n g the m i x i n g process (20). T a l c and

g r a p h i t e have a laclinar p a r t i c l e s t r u c t u r e , but have no e f f e c t

on t a b l e t crushing strength. T h i s u y p o s s i b l y be explained by

the f a c t that t h e i r c r y s t a l s shcm no l a y e r l a t t i c e c r y s t a l

s l i p p i n g by shear b u t a r o l l e r mechanism (23, 24).

The e f f i c a c y o f the l u b r i c a n t s was i n v e s t i g a t e d by measuring

the moximua force r e q u i r e d t o e j e c t the t a b l e t s from the d i e

1.e. the e j e c t i o n f o r c e a f t e r compressing the blends on the

e c c e n t r i c press. Tablets w i t h o u t l u b r i c a n t were prepared i n the

c a r e f u l l y cleaned d i e of the press, which was d r i v e n by hand.

Table 2 s u m u r i z e s the e f f e c t o f m i x i n g the placebo m i x t u r e w i t h

0 . 5 or I b l u b r i c a n t on both crushing s t r e n g t h and e j e c t i o n f w c e .

I t can be seen t h a t e j e c t i o n forces lower than 300 N c o u l d o n l y

 TABLET UIBRIcA"?3 25

TABLE 2

E f f o c t of mixing r l t b 0 . 5 or 1.0% lvbricut oa cruulrinK s t r u n g t h

nnd ojmction f o r c e of tablota irm b l o r d . containing SOS lactoae
1.F.c.. ma STA-RX i#)o u d zw elc- G 250.

Mixing t i u : 2 rin Mixing t i H : 1 O mln Mixing time:= ria

Lubricant
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Crushing Ejection CnuhAng P j o c t i o n Cruahing O j o c t i o n

s t r e w t b forco(N) s t r e n g t h fOr8O(Y) 8trOagth forco(Y)
(kc) (kc) (kg)
no lubricant 11.0 670 11.0 670 11.0 670

0.5% gr8phi t o 8 b b b b

1.0% g r a p h i t 0 a a 12.4 1720 12.3 1680

0.5% talc b b b b b b

1.0% t8lC b b b b b b
For personal use only.

0.5% P.T.P.K. b b b b 10.8 880

1.0%P . T . I . P . 11.5 340 11.0 370 10.8 340

0 . 5 % 1-leucimo b b b b b b

1.0% l-loucine b b b b b b

o.8a ~ t o r o t u 9.2 620 5.6 WO 5.0 450

1.0% B t o m t u 7.3 176 4.0 130 3.7 120

0.5% Cutina HR 6.7 440 5.6 440 4.5 510

1.0% C u t i n a IiR 5.8 300 4.0 280 3.7 aoo

0 . 5 % Boemon VP 7.9 150 4.6 170 2.0 110

1.0% Boamon VP 7.n 1WI 2.7 <lo0 2.1 <loo

0.5% P r b c i r o l 8.9 210 3.0 250 1.0 280

1.01 P r b c i r o l 4.4 iin 2.2 <loo C C

0 < 100

0 < loo

8- t 8 b l o t t l n c machino d r l v v a by b m d , b- inuufflcimnt l u b r l c a t i o n ,

c- i n s u f f i c i e n t flowabillty .
 26 WUIUIS. LERK. AND BROERSUA

be obtained with I2 Sterotax or Cutina HR and 0 . 5 - 1 % of

Doem W , PrCcirol or m a g m r i u stearate. The results show that

ttw ejection Force hardly changes with an increase in airing time.

The lubricating propsrtler o f graphite. talc. P . T . F . E . and

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I-lwcinm were insufflcicnt far the concentrations studled.

Table 2 shows that the decrease In cjectlon force Is roughly

proportional to the decrease In crushing strength for each miring

time. I t can be concluded that, with respect to bath crushing

strength and ejection f o r c e , 1 % Sterotex and 0.5 - 1% Bocson VP

gave the best results when mixed f o r a short per od with the
For personal use only.

other vehicles.

The lubricants Sterotex and b e s o m VP were hen avaluated and

compared with a a g n e s l u staarate In three direct compressible

tablet f o r u l a t l o n s (table 3 ) with a low, a medium high and a high

dose drtiq. respectlvcly.

TMLZ 3
T a b l e t Zorrulmtionm usrd.

Pr.dalmonr 2.5% 2.5% P u m c e t uol 69.93%

Lactose X . I . C . 71.5% 72.0% Avlcml PH 101 29.72%
Awic.1 PH 101 25.0% 2S.W Lubricaat 0.35%
Lubrlaat 1.0% 0.5%

Phnobmrbi too 2s. 0% 25.0%

Amylose V 20.0% a0.m
Cmcaprrm 54.5% 54.0%
Lubtl e m t 0 . s 1.a
 TABLET LUBRIcANls 27

The tables 4 and 5 sumarize the ejection force and Lablet proper-

t i e s of p r e d n i s w and phmbarbitone tablets w i t h 0.5% 11wgnc5i~~,

stearate, 12 b e s o n VP or 12 Sterotax, respectively, as lubricant.

The corpomnts without lubricant had b e i i blended for 30 ain. in

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the cubic tubling mixer. The r8rultr show that an additional

m i x i n g time of 5 minutor with a lubricant uas sufficient for

obtaining a low ejection force. Longer mixing gave a corres-

ponding decrease in crushing strength of the t a b l e t s . diereas

the ejection force hardly changed.

For personal use only.

TABLE 4

tffoct of mixin( w i t h lubricant om ajuctioa foroo,

crushing atruyth, friability and disintrgration tima,
respoctl.voly, of prodnioooo trblota.

Lubricant Mixing Ejoction Crushing YriSillty Dimintogration

,tin Soraa atrrnyth ti&.
bin.) (W (kg)
(I) (a1
no lubricant') - 1750 s.s GO.1 8

1% Booson VP S im 8.7 <O.l 20

15 190 8.4 <o. 1 16

1% Storotox 5 2m 8.1 0.2 14

15 300 7.4 <o. 1 13

180 5.6 0.1 12

150 4.7 0.5 90

A) tablotting mAcbino drlvon by hand

 28 BOLHUIS, LERK, AND BROERSHA

In coqmrison w i t h O . S % ' U ~ M S I U s t e a r a t e , 1% Bocson VP or It

S t e r o t e r gave l e s s decrease i n crushing s t r e n g t h , whareas the

other t a b l e t p r w r t i a s had hardly changed when coqmred w i t h

t a b l e t s containing m a g n e s 1 u s t e a r a t e . Tables 4 and 5 show that

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M i t h respect t o both crushing s t r e n g t h and e l e c t i o n f o r c e , the best

r e s u l t s ware obtained w i t h 1% Boesm VP as l u b r l c a n t .

TABU 8

P t f u t of mixing with lubric-t on o j u t i o a forco, cru8blng

For personal use only.

mtrongth, friability amd di8intmgration t i M , r o 8 p r c t i v o l y ,

Of pbowb8rbltomo t . b l O C 8 .

Lubrlclat Mixing KjWtioa Crushin8 T r i ~ b l 1 l t yD l 8 i n t o c r a t i o n

tin fore. rtroagtb t im.
(%I
-
(mla.)
-
(W (kg) (8)

no lubric.nta) - 1140 6.2 0.4 3

1% Boomoo VP 5 < loo 6.0 0.5 210

18 c 100 4.6 0.7 160

1% Storotax 5 180 6.0 0.9 275

15 180 4.1 1.1 170

0.5% rw08iu 5 < loo 4.1 0.6 180

8t08r.t.
IS loo 1.2 1.1 180
c

a ) t a b l o t t i n e ~ a c h l n odrivrn br band.
 TABW LUBRIcMm 29

T h e paracetam1 formulation ( s e e table 3 ) u s Originated

from the F.H.C. Corporation with 0.352 stearic acid as lubricant

( 2 5 ) . C m p a r I r o n w i t h the three other lubricants (table 6) shows

t h a t replaccrmt of r t u r i c acid by 0.35% of the othar lubricants

Drug Dev Ind Pharm Downloaded from informahealthcare.com by Mcgill University on 01/06/15

caused an even l a r g e r decrease o f the ejection force. Addiiion

of u g n e s i u s t e a r a t e had a v e r y deleterious effect on crushing

strength and friabllity, even h e n this lubricant was rixcd for

a short period with the other inpradients. TLw rcrults s h o n that

b e s o n VP and Starotex caused not I o r e than a mall decrease i n

For personal use only.

TABU 6

li1-t of l f x i a g with l u b r i c a n t on e j w t i o a f o r c e , c n a h l n g
r t r e l y t h , i r i a b i l i t y and d i a i n t e g r a t i o a tire, reapactiv.ly,
or puUIet-1 ta1.t..

D Joct i on Cnuhing P r i A b i l i t y Uiaintegrati

force atrrryth tiu
(%)
-- (N) (kg1 (a)
1140 10.1 1.2 90
480 1o.s 1.2 32
420 10.5 0.8 60
300 9.5 0.7 la
340 6.5 1.3 23
380 9.3 1.l 24
340 8.8 0.8 23
350 3.3 3.1 21
400 2.3 4.8 21
 30 BOLHULS, LFBK. AND BROERSMA

tablet hardness, when the airing time was short. In comparison with

stearic acid, these lubricants a r e advantageous with respcct to

both ejection force and dlsintegratlon tins of the tablets.

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tOtK1US I ows
--

O f a series of lubricants tested in a direct compressible

systeca. a11 the lubricants except talc, graphite and polytetra-

fluoroethylene decreased the binding forces of the excipients

with an increase in mixing time o f the blends. Just as previously

reported for magnesium stearate. Hydrogenated vegetable o i l s ,

For personal use only.

glycerides snd m a g n e s i u stearate, which gave the lowest ejection

forces, caused the largest reduction in tablet strength with an

increase in mixing time. in concentrations of It, Sterotex,

Boeron VP and Precirol gave about the same reduction of ejection

force as 0 . 5 % magnesium stearate. but -in spite of the higher

concentrations, in which they were used- their effect on tablet

hardness during nixing was ruch smaller. Examples of direct

cagreasible tablet formulations show that i t can be advantageous

to replace magnesium stcarate by Sterotex or Boason VP. CIOod

lubrlcation and tablet properties a r e obtained after a short mixing

o f . lubricant with the blend of other tablet ingredients.

in addition, the mixing time is less critical than when magnesium

stearate was used.

 TABLET LUBRKCAN?S 31

FOOTWOTES

1. f.fi.C. Carporation, h e r i c o n Viscose Division, b r k u s Hook,

Pa., U.S.A.

2. Oegussa, Frankfurt a. n.. West CarvJny.

Drug Dev Ind Pharm Downloaded from informahealthcare.com by Mcgill University on 01/06/15

3. A.E. Stalcy nfg. Co., Odcatur, Illinois. U.S.A.

4. Avcbe G.A., Weendam.

S. Edward Hendell Co.. Inc., New York, U.S.A.

8. B.V. Hollandsc Hetkkruikerfabriek, Uitgaert .

7. L o w r s en Indemans, Is-Hertogenbosch.

8. Croda W. , kttetal, West Germany.

For personal use only.

8. B.D.H. Chemicals, Poolc, England.

10. EtabIiss~ntr(;1ttefoss~,Saint-Priest, France.

11. Capital City Products t o . , Coluarbur, Ohio, U.S.A.

12. C.H. Boehringar Sohn. lngelheim a . R . , Vest b r u n y .

13. Henkel C Cis. W H . , Diisscldorf. West Gemany.

14. Aldrich-Europe, Beerse. Belgium.

15. Hogupha, A l h a r .

16. O.P.G., Utrecht.

17. M e i 930, B c c h n Instruments tied. W . V . , AlPsLerdaat.

18. Parkln Elmer Sorptometer, model 212.

19. Node\ ZP, U.A. Bachofsn, Baslc, Switzerland.

REFERENCES

1. E. Nelson, S.H. Naqvi, L.W. Bussc and 1.. Higuchi, J. Am. Phara.

Assoc., Sci. Ed. 2, 596 (1954).

 2. U.A. S r r i c k l a n d , J r . , E. Nelson, L.Y. Busre and T. H i g u c h i ,

Ibidem 45.- 51 (1956).

3. W.A. S t r i c k l a n d , Jr., T. Higuchi and L.W. -

Busse, Ibidem 49, 3 5 (1960)

4 . 0. Aipar, J.J. Dear. J.A. Horsey and E . Shotton, J. Phrm.

Drug Dev Ind Pharm Downloaded from informahealthcare.com by Mcgill University on 01/06/15

-
Phamacol. 2 1 , 6 s (1%9),

5. A. La k n n a and E . S h o t t o n , I I Frmaco. Ed. P r . 25, 689 (1970). -

6. E. Shotton, Pharm. Ind. 34, - 256 (1972).

7 . A. S t a m and C . H a t h i s , L a b - P h r m a no. 250, 61 (1976).

8. E. H a r t m e and R.F. Shangrau, J. P h r m . S c i . 6,498 (1967).

9. E . Cid and F. Janinat, J. Phara. Belg. 2 6 , 360 (1971).

For personal use only.

10. H. Dcionca. J. Joachim, C. Jorchim and A. Cantos, I I Farrrmco,

-
Ed. P r . 3 0 , 89 (1975).

1 1 . Techn. b u l l . "Grundstoffe f l l r d i e PharmaricU Roglster 7 . Henkel.

Dilsseldorf (1975).

12. F . Jaminct and A . H a t i c , Pharn. Acta H e l v . 41. 530 (1966).

13. F. J i n i n e t and C. Evrard, Ibldam 41, 601 (1966).

14. Techn. b u l l . CattefossC. n o t i c e OL 0079 (1970) "Excipiants pour

forms g a l h i q w s siiches".

I S . Tcchn. b u l l . Boason VP, C.H. Boahrinaer Sohn. i26-5/780-EH.

16. J. P a r i s , t h e s i s P a r i s (1974).

17. L. O t l a t t r e , J. C i l l r r d , F. J w i n e t and H. Roland, J. Pharm.

-
Belg. 3 1 , 497 (1976).

18. A . Staam, A. Klelnknecht and 0 . BobbC. Lab-Pha- no. 263, 2 1 5

(1977).

19. C.K. Bolhuls, C.F. Lcrk. H.T. Z l J l s t r a and A.H. dc Boer, Pharm.

-
Weekblad 110, 3 1 7 (1975).
 TABLET IlIBBICANTS 33

20. C.F. Lerk, C.K. Bolhuir and S . S . Saedeaa. Phrn. Acta Halv. 52.
33 (1977).

2 1 . H. Croenwold, C.F. Lark and R.J. Nuidcr, J . Pharr. Pharuccrl.

-
24, 3 5 2 (1972).

-
Drug Dev Ind Pharm Downloaded from informahealthcare.com by Mcgill University on 01/06/15

22. C.F. Lark and G.K. Bolhuir, Phara. Acta H a l v . 5 2 , 39 (1977).

23. U. B o I l v n n and J. Sprudborough, Nature (London) 186, 29 (1960).

24. 0. Train and J.A. Harley. J. Phara. P h a r u c o l . El 97T (1960).

25. Tachn. B u l l . A v i c a l , PH 9, F.H.C. Carp. (1974).

For personal use only.