TECHNOLOGY

T H E W O R K OF M O U L D I N G M E D I C I N A L G R A N U L A T E S

V. I . E g o r o v a UDC 615.453.3.014.21

The m e a s u r e m e n t of the work of moulding medicinal granula tes is of p rac t i ca l impor tance for eva lua t - ing the economic indices of different technological p r o c e s s e s in the p r epa ra t i on of tablets . In o rde r to ob- tain high-qual i ty tab le ts with the sma l l e s t consumption of energy (at lower moulding p r e s s u r e ) , f i l l e r s a re added to the powder to be tableted, and granulat ion and drying a re c a r r i e d out, which enable g ranu les of the opt imum dimens ions and with the opt imum res idual moi s tu re content to be obtained. A cons iderably g r e a t e r moulding p r e s s u r e is r equ i red for moulding dry and fine powders . In a number of ca ses , the consumption of energy in moulding is so high that it is imposs ib le to obtain a f i r m tablet.

The work of moulding medicinal g ranula tes can be de te rmined f rom an indicator d i ag ram obtained f rom a c o m p r e s s i o n exper iment . In the c o m p r e s s i o n exper iment (Fig. 1), the granules a re filled into a m a t r i x with a c r o s s - s e c t i o n a l a r e a S. The i r initial height before moulding is h i. Under the action of the moulding force Q, the granules a re compacted and the i r height in the ma t r i x d e c r e a s e s . The instantaneous height of the granules in the m a t r i x under the moulding p r e s s u r e P is h m. In the indicator d i ag ram (Fig. 2), the c o m p r e s s i v e force Q is plotted along the axis of ord ina tes and the deformat ion of the granules h along the axis of absc i s s a s . The e l e m e n t a r y work of moulding dA during the movement of the punch by a d i s - tance dh is equal to the hatched a r e a of the d iagram:

dA = Q.dh=P.S .dh .

According to Fig. 1, the deformat ion of the granules h = h i - h m and, consequently, dh =dhm. F r o m this,

dA = - - P .S .dh

The economic indices of the moulding p r o c e s s a re bes t evaluated f rom the specif ic work of moulding con- sumed in the product ion of 1 g (or 1 kg) of tablets . This is one of the mos t impor tan t c h a r a c t e r i s t i c s of the compacted granula tes .

The e l e m e n t a r y specif ic work of moulding

aA (1) dAsp- - ra = - - P 'dV '

where m is the weight of the tab le ts and dV is the i nc rea se in the specif ic volume of the granules under p r e s s u r e (the minus sign shows a dec r ea s e in the specif ic volume with an i nc r ea se in the moulding p r e s - sure). To de te rmine the specif ic work of moulding we mus t have the re la t ionship between the change in the specif ic vo lume of the granules and the moulding p r e s s u r e . We have found this re la t ionship for the region of p las t ic and b r i t t l e de format ions p rev ious ly [1]. It is e x p r e s s e d by the equation:

V = Vi -- Cc .l~im'ln P, (2)

where Vi is the specif ic volume of the granules before moulding; Vlim is the l imit ing specif ic vo lumes of the granules at 100% compact ion; and C c is a coeff icient cha rac t e r i z ing the physica l p r o p e r t i e s of the granules on compact ion (it is de te rmined exper imenta l ly) .

The numer i ca l value and the d imensions of the coeff icient C c depend on the choice of the sys t em of units in which the moulding p r e s s u r e P is measured . To de te rmine the specif ic work of moulding f rom [Eq. (1)] it is bes t to give the moulding p r e s s u r e in d imens ion less units:

Leningrad Insti tute of P ha rm aceu t i c a l Chemis t ry . Trans la ted f rom K h i m i k o - F a r m a t s e v t i c h e s k i i Zhurnal , Vol. 5, No. 8, pp. 36-40, August, 1971. Original a r t i c le submit ted May 14, 1970.

�9 1972 Consultants Bureau, a division o f Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. Al l rights reserved. This article cannot be reproduced for any purpose whatsoever without permission o f the publisher. A copy of this article is available from the publisher for $15.00.

486

t Q

2 006

1800

1200

"~ 800

C~ 400

--4

EO 120 180 240 300 050 420 h , /O Z m m

Fig. 1 Fig. 2

Fig. 1. Composition of granules in moulding. 1) Punch; 2) material.

Fig. 2. Relationship between moulding force Q and deformation of the granules h.

Vsp, crn3 / g

,5 I 1,5 - - i - -

I

I,!

,.o

0,9) 3 4 E ZnP

420

2~

P, kgf/cm z

830

I . . . .

UO 1.22 L84 ~A8 ~68 Vsp, cm~/g

Fig. 3 Fig. 4

Fig. 3. Dependence of the specific volume of the granules Vsp on the log- arithm of the moulding pressure P.

Fig. 4. Relationship between the specific volume of the granules and the moulding pressure P.

P v = vi - c 0 . v . r ~ l ~ - ~ - ,

where C o is a dimensionless coefficient and Pi is the pressure at which the initial specific volume of the granules is measured.

F r o m Eq. (3)

(3)

whence the moulding p r e s s u r e

p Vi -- v

In = Pi - CoVlirn'

Vi - - V

P = Pi .e C~

By substi tuting the value of the moulding p r e s s u r e P in Eq. (1) in o rde r to de te rmine the speeif ic work of moulding, we have

v i -- v

-Co :Vli rn dA ~ Pi .e .dV.

487

TABLE I. Work of Moulding the Granules (in kgf. cm/g)

i / between caI-

Work of moulding ] culatiom from K ~ ._= Eq~. (6) ~d (8)

33 2, 87 40 3,72 3, 60 8,16 7,2 , , , 6 ,9

,oo ,,04 1208,22 , ,6 ,o 200 23,24 24,28 24,4 1,16 5 300 36,44, 36,48 36,6 1,16 3,4 500 59,84 60,9 61,0 1,16 1,9

1000 20,841 21,9 22,0 1,16 0,96 I

TABLE 2. Values of the Specific Work of Moulding (in kg- cm/g) for Granules of Ci t ramon at Various Moulding P r e s s u r e Determined by Var i - ous Methods

., ~ Work of moulding

.. ~ ~q by numee- by graph- ~ ~ ical inte- ical inte-

;~ ~ .1 ,~ r ~ ~ ~~ .~= o~ gration gration

167 292 417 588 664 750 833

23,7 22,5 (6,7) 21,8 33,1 33,3 (0,6) l 33,7 45,t 45,0 (0,2) l 41,7 59,2 54,2 (9,3)I 57,5 63,3 59.0 (4,0){62,3 67,8 64,7 (4,8)J 67,9 72,5 70,9 (2,3) ] 74,2

I

(8,81 (0,8) (0,8) (3,o) (4,o) (4,8) (2,3)

Note. The f igures in bracke ts are the d iscrepancies (in %) between the resul ts of the given method and the values de te r - mined f rom Eq. (8).

or

Integrating this equation from V 1 to V2, we obtain

i t V i - V V i --V V~

Asp =--Pi G'Vlim" dV Pi "Co'Vlime c~ ]

{ v i - v~ vi - v,

where V 1 and V 2 are the specific volumes of the granules at moulding p r e s s u r e s t) i and P2.

The stage of plastic compress ion is preceded by a p r e c o m p r e s - sion stage in which the granules approach one another and are com- pacted without their deformation. In this stage at low moulding p r e s - sures a relat ively large change in the specific volume of the granules is found (see Fig. 2). To determine the work of moulding at this stage, we recorded indicator d iagrams at low moulding p re s su re s . As can be seen f rom Fig. 3, the change in the deformation of the granules as a function of the logari thm of the moulding p r e s s u r e at the p recompres s ion stage obeys the same law as in the plastic mould- ing stage, but the straight line has a different slope [1]. On this basis , for the p r ecompres s ion stage it is possible to wri te the following equations:

V i -- C~p. Vlimln ~p, (5) [ v i~Vp

Asp = Pi "Cop'Vlim ~ e' '~~ 1) '

where V~ and A__ are the specific volume and specific work of mould- p ~p ing at a moulding p r e s s u r e P in the p recompress ion stage.

The total specific work of moulding for the p recompres s ion stage and the plast ic compress ion stage is

Asp = Asp + Asp. (6)

where Asp is the specific work in the plast ic compress ion stage.

To simplify actual engineering calculations, it was decided to do without the separate calculation of the work in the p recompres s ion

stage of the p r oce s s and to consider that all the work f rom V i to Vf is given by the law of plastic compress ion. In this case, V i = Vi, and Eq. (6) a ssumes the form:

v i - v ) (7) Asp ~Pi.Co-l~i m e c~ "

In view of the fact that the magnitude V - - V

C)- V H i3~ is considerably g rea t e r than unity (by a fac tor of

500 and more), in calculation by means of Eq. (7) it is possible to neglect unity. In this case, the formula assumes the form:

Asp = Pi �9 CO. Vlim e

V i -- V Co. Vlim. (s)

Table 1 gives values of the work of moulding calculated f rom Eqs. (6)-(8).

488

As can be see f rom Table 1, the absolute values of the e r r o r in the determination of the work of moulding f rom Eqs. (6) and (8) is a constant magnitude. The relat ive e r r o r dec reases with an increase in the moulding p re s su re , and at working p r e s s u r e s used in the prepara t ion of tablets does not exceed 1% (in the direct ion of a margin). Consequently, for engineering calculations of the specific work of moulding the approximate equation (8) may be recommended. The total work of moulding

A = Asp-m-" vi - v (9 ) Co. Vlim _

A = ~ Co.Vlime .m,

m

where m is the weight of the tablet.

The experimental determinat ion of the work of moulding of granules can be per formed f rom the indi- ca tor diagram. Its calculation can be ca r r i ed out by graphical or numer ica l integration. In the indicator d iagram (see Fig. 2), the ordinates a re proport ional to the moulding forces Q and the absc i ssas to the d is - placement of the punch relat ive to the matr ix h. Thus, the indicator d iagram is a graphical i l lustrat ion of the function Q = f(h).

The total work of moulding with a displacement of the punch by a distance h 2 - h 1 is

h~

A ~ i 'P .S .dh ,

where h i and h 2 are the deformations of the granules at moulding p r e s s u r e s 1~ and t) 2. On the appropriate scale, this integral is equal to the a rea included within the indicator d iagram from h 1 to bq. The graphical determination of the specific work of moulding can be pe r fo rmed from the graph of the relationship P = f(V) (Fig. 4).

As an example, in Table 2 values of the work of moulding are given for granules of c i t ramon calcu- lated f rom Eq. (7) and determined by numer ica l and graphical integrat ion f rom the moulding diagram. It follows f rom Table 2 that the values calculated analytically f rom Eq. (8) agree sat isfactor i ly with the values determined direct ly f rom the indicator diagram.

Below we give values of the specific work of moulding (in ki lograms force , cent imeters per gram) of granules of var ious preparat ions . Moulding was ca r r i ed out at a p r e s su re of 833 kgf /cm 2.

Ci t ramon . . . . . . . . . . . . . . . 72.5 Amidopyrin . . . . . . . . . . . . . . 73.5 Urotropin . . . . . . . . . . . . . . . 118.0 Belladonna extract . . . . . . . . . 54.0 Guaiacol carbonate . . . . . . . . . 108.0 Aspir in . . . . . . . . . . . . . . . . . 96.0 Phenacetin . . . . . . . . . . . . . . 100.0

As can be seen different pharmaceut ica l granulates differ substantially in the energy consumed in their moulding.

I.

LITERATURE CITED

V. I.Egorovaand B. A. Loksin, Khim-Farmats. Zh., 3_, No. ii, 58 (1969).

489