Comparaison of native starches as tablet disintegrant

COMPARAISON OF NATIVE STARCHES AS TABLET
DISINTEGRANT
O. Häusler1 , Ch. Brockmann2, H. Rein2
1 Roquette Frères, 62080- Lestrem, France
Email olaf.haeusler@roquette.com, Tel +33 (321) 63-3753
2 Rheinische Friedrich-Wilhelms-Universität Bonn, Germany Institute of Pharmacy
Native starches are extensively used as a
disintegrant in tablets. Their action passes via an
immediate swelling when wetted with aqueous
liquids. Starches are isolated from raw materials
of different botanical origin and they have
therefore different physicochemical properties
such as particle size or humidity. These
differences could modify their functionality as
tablet filler and disintegrant. The new EP edition
(2009) completes the range of pharmacopeial
starches with pea starch, isolated from pea (Pisum
sativum L.). Comparative trials between several
starches could assist the excipient choice. Tests
were done with a soluble (lactose) and a non
soluble (phosphate) tablet binder system.
EXPERIMENTAL METHODS
Materials
Commercial excipients Dicalcium phosphate
dihydrate (Emcompress® from JRS, Germany),
agglomerated lactose (Tablettose® 70, Meggle
GmbH, Germany), commercial pea, potato and
maize starch from Roquette Frères, France, and Mg
stearate from Bärlocher GmbH, Germany were used
without further purification. All products are in
conformity with the EP monographs.
Tableting and Tablet Analysis
The powders were blended for 2 min in a Turbula
mixer (Type T2C, Willy A. Bachofen AG,
Switzerland) and compressed on a pneumo­
hydraulic press FlexiTab® 2080 (Röltgen GmbH,
Solingen, Germany) equipped with flat punches,
diameter 10 mm. The filling depth was constant
with 8 mm causing minor tablet weight variations
due to difference in powder flow. Generally three
different starch concentrations (5%, 10% and 15%)
were tested using 0.5 % Mg stearate as lubricant.
The tablet crushing strength was measured with a
TBH 210WTD (Erweka GmbH, Germany) with
fresh tablets (one day after compression) and also
after one week and three month of storage at 25°C
and 60% relative humidity.
Tablet porosity was calculated from the dimension
of the tablet using the relative density of the powder
blend, measured with helium in a pycnometer
(Ultrapycnometer 1000 T, Quantachrome, Germ.).
Disintegration, according to the EP methods, was
carried out, using the Erweka ZT 72 (Erweka
GmbH, Germany) equipment. The mean value for 8
tablets was calculated.
RESULTS AND DISCUSSION
Tablet Crushing Strength
Hard Tablettose 70 tablets were obtained with all
starches and all tested concentration with a min.
tableting force of 20kN. The observed weight
variation of the tablets was between 2.5 and 5.5
mg (for a mean tablet weight of 420-440 mg),
increasing with the starch concentration. The
starch ratio had no major impact on the initial
tablet crushing strength at a given compression
force. Tablets made with maize starch had
generally lower tablet hardness than those made
with pea or potato starch.
Storing lactose tablets (with or without starch) for
1 week or 3 month showed a post hardening
effect. It was much more significant in presence
of maize starch but minor for pea and potato
starch (see figure 1).
Figure 1: Post hardening of Tablettose 70 tablets
containing either 15% pea starch or 15% maize
starch
250
Tablet Hardness [N]
INTRODUCTION
200
150
15% Maize starch -fresh
100
15% Maize starch - 3 month
15% pea starch - fresh
50
15% pea Starch - 3 month
0
0
10
20
30
40
50
60
Compression Force [kN]
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Similar observation has been made with the
insoluble phosphate. Sufficient hard tablets were
obtained above a compression force of 15kN.
Modifying the maize starch concentration had no
influence on the tablet hardness, similar to that of
starch free tablets. Increasing the potato starch
concentration reduces progressively the tablet
crushing strength. The observed tablet weight
variation was between 2.5 and 6 mg (for a mean
tablet weight of 650-700 mg), increasing with the
starch concentration. This is due to an improved
powder flow when adding starches. A post
hardening effect in presence of starches was
detectable, but lower than that for lactose.
Maize starch and pea starch turned out to be the
best disintegrants for the insoluble phosphate.
Very short disintegrations times were always
obtained with 5% starch. Increasing its ratio up to
15% did not significantly accelerate the tablet
disintegration. Potato starch shortened the
disintegration time as well, but in a lower extend
(see figure 4). The reason could be a partial
pregelatinization of potato starch during tableting
and storage, creating soluble parts.
Figure 4: Disintegration of Emcompress tablets
containing 15% of maize, pea or potato starch, fresh
and after 3 month storage
180
15% Maize starch -fresh
Figure 2: Disintegration of Tablettose 70 tablets
containing 15% of maize, pea or potato starch, fresh and after 3 month storage.
Disintegration time [s]
70
60
50
15% Pea starch - fresh
120
15% pea Starch - 3 month
100
15% Potato starch - fresh
15% Potato starch - 3 month
80
60
40
0
0
10
0
10
20
30
40
Compression Force [kN]
50
60
20
18
16
14
12
10
8
15% potato starch - fresh
6
4
15% potato starch - 3 month
10
20
30
40
50
60
Summary
60
18
16
14
12
10
15% Maize starch -fresh
15% Maize starch - 3 month
15% pea starch - fresh
2
50
Compression Force [kN]
Figure 3: Porosity of Tablettose 70 tablets
containing 15% of maize or pea starch, fresh and
after 3 month storage.
4
30
40
Compression Force [kN]
Figure 5: Porosity of Emcompress tablets containing
15% potato starch, fresh and after 3 month storage.
0
15% Maize starch -fresh
15% Maize starch - 3 month
15% pea starch - fresh
15% pea Starch - 3 month
15% potato starch - fresh
15% potato starch - 3 month
20
6
20
0
30
8
10
The porosity of phosphate tablets increases when
adding granular starches. This is the effect of an
elastic recovery of the starch particles.
With storage at 60% relative humidity, the
porosity of the tablets increased slightly. The
higher porosity does not explain the observed
reduction of the tablets disintegration speed.
2
40
0
Tablet Porosity [%]
15% Maize starch - 3 month
140
20
Tablet Porosity [%]
The used starch type had no major influence on the disintegration time of fresh lactose tablets.
The disintegration times were comparable for all
starch concentrations. Nevertheless, with storage
occurs a prolongation of the disintegration time
(see figure 2), especially at higher compression
forces. The rank order was potato starch > maize
starch > pea starch.
The starch origin and its used concentration had
no influence on the porosity of fresh lactose
tablets. During storage, the porosity of lactose
tablets remained in the same range. The
progressive prolongation of the disintegration
time can therefore not be correlated with eventual
modifications of the porosity. It could be
attributed to the observed post hardening.
Disintegration Time [s]
160
Tablet Disintegration
All three tested pharmacopeial starches are
valuable tablet disintegrants. The concentration of
5% was sufficient for guaranteeing short tablet
disintegration. However there are significant
application differences, depending on the used
tablet excipients. A careful selection of the most
adapted starch type and its concentration is
recommended. Pea starch is an interesting
alternative to the widely used maize and potato
starch.
15% pea Starch - 3 month
0
0
10
20
30
40
50
60
Compression Force [kN]
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