Pharmaceutical Manufacturing Handbook: Production and

888 PHARMACEUTICAL PREFORMULATION
TABLE 3
Granulating Agent
Starch
Pregelatinized starch
Acacia
Commonly Used Granulating (Binding) Agents
Polyvinylpyrrolidone
(PVP)
Hydroxypropyl
methylcellulose (HPMC)
Methylcellulose (MC)
Normal
Concentration
(%)
5 – 25
0.1 – 0.5
1 – 5
2 – 8
2 – 8
1 – 5
Comments
Was once the most commonly used binder;
starch has to be prepared as paste, which
is time consuming
Cold - water soluble so easier to prepare
than starch
Requires preparation of past prior to use;
can lead to prolonged disintegration
times if used at too high a concentration
Available in range of molecular weight/
viscosities; soluble in water and ethanol
Low - viscosity grades most widely used
wetting of hydrophobic drugs. However, if added at too great concentrations, the
fi lms can form viscous gels on the granule surface and will retard dissolution.
Disintegrant Tablets must have suffi cient strength to withstand the stresses of
subsequent manufacturing operations, such as the coating, packaging, and distribution
process. However, once the tablet is taken by the patient, it must break up
rapidly to ensure rapid dissolution of the active ingredient in immediate - release
preparations. To overcome the cohesive strength produced by the compression
process and to break down the tablet into the primary particles as rapidly as possible,
the disintegrants are combined with other excipients during the tableting process.
Starch was the fi rst disintegrant used in tablet manufacture. Recently, so - called
superdisintegrants, including croscarmellose sodium, sodium starch glycolate, and
crospovidone, display excellent disintegration activity at low concentrations and
have better compression properties than starches. Traditionally, swelling and rate of
swelling have been regarded as the most important characteristics of disintegrants.
With the aid of these superdisintegrants, sustained - release acetaminophen tablets
with biphasic patterns were successfully established to mimic the bilayered Tylenol
ER tablet [9]. As a general rule, soluble drugs are formulated with insoluble fi llers
to maximize the effect of disintegrants. The positioning of disintegrants within the
intragranular and extragranular portions of granulated formulations can affect their
water uptake and disintegration time.
Commonly used disintegrants are listed in Table 4 . The greater the level of disintegrant,
the faster the tablet will disintegrate. The compaction properties of many
disintegrants, including starch, are not satisfactory and use of high concentration
could also reduce tablet strength. Disintegrants are hygroscopic materials and will
absorb moisture from the atmosphere, which could negatively affect the stability of
moisture - sensitive drugs if the packaging does not provide adequate protection
from the environment. Disintegrant activity can be affected by mixing with hydrophobic
lubricants so that care needs to be taken to optimize the manufacturing
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