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Excipients & Actives for Pharma
No. 26, 2011
CROSPOVIDONE
Binding properties and flow behavior of
different crospovidone grades
C.Tissen, M.Hilkens, J.Lorenz, P.Kleinebudde Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University Duesseldorf, Germany
INTRODUCTION | Crospovidone is a superdisintegrant
commonly used in quantities of 2-5 %
(w/w) to accelerate the disintegration of tablets.
Several grades of Kollidon CL are commercially
available and differ only in particle size distribution.
The drawbacks of traditional disintegrants
are often poor flowability or a negative influence
on the compactibility of tableting mixtures.
However, robust mechanical properties and low
friability should be achieved in order to facilitate
further production steps, e.g. coating processes.
Therefore, a combination of a dry binder and a
disintegrant is often required to improve the
mech anical properties of a tablet while still ensuring
complete disintegration.
The purpose of this study was to investigate the
binding properties of crospovidone grades of
different particle size distributions and elucidate
their influence on tensile strength.
METHODS AND MATERIALS | Materials
Crospovidone (Kollidon CL, Kollidon CL-F,
Kollidon CL-SF, BASF SE, Ludwigshafen, Germany),
alpha-lactose monohydrate (Tablettose ®
80, Meggle, Wasserburg, Germany), dicalcium
phosphate (Dicaphos ® AN, *Budenheim, Germany),
magnesium stearate (Welding, Hamburg,
Germany).
Methods / Particle size distribution The particle
size distribution of the various Kollidon CL
grades was analyzed using laser light diffraction
(Helos, Sympatec GmbH, Clausthal-Zellerfeld,
Germany). Measurements were performed in
triplicate with a dry dispersing unit (Vibri, Rhodos
T4.1, Sympatec GmbH, Claustha-Zellerfeld,
Germany) at 1.0 bar.
Flowability The flowability of the tabletting mixtures
was analyzed in duplicate with a ring shear
tester (RST-01.c, RST-CONTROL 95 Schulze
Schuettguttechnik, Wolfenbuettel, Germany).
Consolidation stress and unconfined yield
strength were used to characterize flowability.
Normal stress during pre-shearing was 5000 Pa.
Compression of tablets Table 1 shows tabletting
mixtures containing different ratios of filler
(Tablettose 80, Dicaphos AN) and disintegrant
(Kollidon CL; Kollidon CL-F, Kollidon CL-SF).
Each formulation was blended for 20 minutes in
a laboratory-scale Turbula mixer (Turbula T2F,
Bachofen AG Maschinenfabrik, Basel, Switzerland).
Afterwards, 0.5% w/w magnesium stearate
was added as a lubricant and the mixtures were
blended for two further minutes.
Each mixture was compressed to flat-faced tablets
of 12 mm diameter at 153 and 255 MPa, using
a rotary die press (Pressima, IMA Kilian, Cologne,
Germany). Crushing forces were determined with
a hardness tester (HT-1, Sotax, Basel, Switzerland)
and subsequently calculated as tensile
strength according to Fell and Newton [1].
TABLE 1
Fraction [%]
Filler 100 95 90 80 60 40 0
Disintegrant 0 5 10 20 40 60 100
Tabletting mixtures
Disintegration testing The disintegration time
for 12 tablets of each batch was measured with
a disintegration tester (Erweka ZT 32, Heusenstamm,
Germany) according to Ph.Eur. Because
of the extreme turbidity of the disintegration
medium after a few seconds, all batches were
analyzed without using a beaker.
RESULTS AND DISCUSSION | Discussion
The tensile strength of the lactose/crospovidone
tablets varied from 0.9 to 5.1 N/mm² (Figure 1).
Irrespective of the amount of Kollidon CL, the
tablets exhibited no increase in tensile strength.
In contrast, crospovidone grades with smaller
particle sizes led to improved tensile strength.
The higher the amount of Kollidon CL-F and
Kollidon CL-SF, the higher the tensile strength
of the resulting tablets. As the particle size of
crospovidone decreased, the detected tensile
strength increased (Figure 2). The tensile strength
of tablets is known to be affected by the variation
in particle size of the excipients used. Smaller
particles facilitate interparticulate bonding during
the compression process, resulting in tablets
with improved hardness [2]. Consequently, tablets
with Kollidon CL-SF exhibited the highest
values. Even 20% (w/w) almost doubled the determined
tensile strength.
All crospovidone grades could successfully
be compressed to tablets without filler; tablets
consisting of pure Kollidon CL-SF exhibited the
highest tensile strength.
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