BASF Fine Chemicals Generic Drug Formulations 1998
also be exploited for the production of concentrated active substance that is
subsequently used for direct tabletting.
Obviously, Kollidon VA 64 and Ludi- press can also be combined with one
another.
2.3 Wet granulation
Great significance is still attached to wet granulation, because direct com-
pressing is not the most suitable technology for many active substanc-
es that are in high dosages or in fine powder form. Even if the active sub-
stance is sensitive to hydrolysis, mod- ern equipment, e. g. in a fluidized
bed, eliminates all problems in wet granulation.
The granules for tabletting of the pre- sented formulations were mostly pro-
duced by traditional means, i. e. mois- tening, screening, drying, and again
screening. Fluidized-bed granulation was resorted to only in exceptional
cases in view of the amounts needed. Various alternatives to wet granulation
in general are offered by BASF phar- maceutical excipients:
– granulation with a Kollidon solution – granulation of a dry mixture of the
active substance and filler and Kollidon with water solvent
– granulation in which some of the Kollidon is mixed with the active
substance and the rest is dissolved in the solution used for granulation
The last the of the three alternatives is preferred if the amount of liquid re-
quired for granulation is restricted and therefore the viscosity of the solution
containing all of the Kollidon would be too high.
Other alternatives consist of using dif- ferent grades of Kollidon. Substituting
Kollidon 25 or Kollidon 30 by Kollidon 90 F would be particularly interesting
for obtaining greater hardness without increasing the pressure. The example
of a placebo tablet illustrated in Fig. 2 shows that tablets of twice the hard-
1,0 0,9
0,8 0,7
0,6
0,4 0,5
Kollidon VA 64 Kollidon 30
Mc. Cellulose HPMC 11000
P la
s ti
c it
y
Plasticity = plastic energytotal energy Force: 18 kN
Force: 25 kN
Fig. 1 Plasticity of dry binders in tablets
99.5 binder + 0.5 magnesium stearate
BASF Fine Chemicals Generic Drug Formulations 1998
ness of those obtained by Kollidon 25 can be achieved by using Kollidon 90
F at low pressures.
Conversely, there would be some point in changing over from Kollidon
90 F to Kollidon 25 or 30 if the vis- cosity of the solution used in granula-
tion is too high. In practice, however, the same hardness is usually achieved
by increasing the amount of Kollidon.
2.4 Tablet press
