TABLET
Disintegrant
Disintegrant is an excipient which is added to a tablet or capsule blend to aid in the break up of
the compacted mass when it is put into a fluid environment. This is especially important for
immediate release products where rapid release of drug substance is required.Disintegrant can
be used with products that are wet granulated, dry granulated and direct compression. In wet
granulation formulations, the disintegrant is normally effective when incorporated into the
granule (intragranularly). It may be more effective if added 50% intragranularly, and 50% extra-
granularly.
The simplest way to achieve quick disintegration is to use a superdisintegrant in concert with
suitable diluents. Superdisintegrants such as croscarmellose sodium, crospovidone, and sodium
starch glycolate are frequently used in tablet formulations to improve the rate and extent of
tablet disintegration and thereby increase the rate of drug dissolution.
There are three major mechanisms and factors affecting tablet disintegration as follows:
A: Swelling:
Although not all effective disintegrants swell in contact with water, swelling is believed to be a
mechanism in which certain disintegrating agents (such as starch) impart the disintegrating
effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is
overcome causing the tablet to fall apart.
B: Porosity and Capillary Action (Wicking):
Effective disintegrants that do not swell are believed to impart their disintegrating action through
porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into
tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to
enhance porosity and provide these pathways into the tablet. Liquid is drawn up or “wicked” into
these pathways through capillary action and rupture the interparticulate bonds causing the tablet
to break apart.
C: Deformation:
Starch grains are generally thought to be “elastic” in nature meaning that grains that are
deformed under pressure will return to their original shape when that pressure is removed. But,
with the compression forces involved in tableting, these grains are believed to be deformed
more permanently and are said to be “energy rich” with this energy being released upon
exposure to water. In other words, the ability for starch to swell is higher in “energy rich” starch
grains than it is for starch grains that have not been deformed under pressure.
It is believed that no single mechanism is responsible for the action of most disintegrants. But
rather, it is more likely the result of inter-relationships between these major mechanisms.
Disintegrants
1. Croscarmellose Sodium (Explotab, Primogel) : High swelling capacity with minimal
gelling, effective at low concentrations ( 2.0% - 6.0%). Above 8%, disintegration times
may actually increase due to gelling and its subsequent viscosity producing effects.
2. Crospovidone (Polyplasdone XL, Kollidon CL) : water insoluble and strongly
hydrophilic. Rapidly disperses and swells in water, but does not gel even after prolonged
exposure. Greatest rate of swelling compared to other disintegrants. Greater surface
area to volume ratio than other disintegrants. Recommended concentration: 1 to 3%.
Available in micronized grades if needed to improve uniform dispersion in the powder
blend. Sometimes, the surface of tablet after compression will be look “pimpled”,
especially in wet granulation.
3. L-HPC (Low-substituted hydroxypropyl cellulose) : Insoluble in water. Rapidly swells
in water. Grades LH-11 and LH-21 exhibit the greatest degree of swelling. Certain
grades can also provide some binding properties while retaining disintegration capacity.
Recommended concentration 1-5%. Sodium Starch Glycolate Absorbs water rapidly,
resulting in swelling which leads to rapid disintegration of tablets and granules.
Recommended concentration: 1.0 – 4.0% but may need to use up to 6.0%. Gels on
prolonged exposure to water. High concentrations may cause gelling and loss of
disintegration
4. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl
cellulose. (Accelerates Dissolution), Nymcel.Wicking due to fibrous structure,
swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 2-
4% (Wet Granulation)
ADVANTAGES:
Effective in lower concentrations than starch
Less effect on compressibility and flow ability
More effective intragranularly
DISADVANTAGES:
More hygroscopic (may be a problem with moisture sensitive drugs)
Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a
problem in-vivo.)
Working Through Disintegrant
The tablets of crospovidone exhibit significantly higher hardness than do those of
croscarmellose sodium. Croscarmellose sodium aids in the disintegration and dissolution
of pharmaceutical tablets, capsules, and granules. Coprocessing has been extensively
examined for diluents.
Croscarmellose sodium and crospovidone were selected in the present investigation
since crospovidone acts by wicking action and croscarmellose sodium acts mainly by
swelling action. Therefore, the superdisintegrants complement each other, accelerating
the disintegration process when used together. The water uptake by the tablet is
facilitated by the wicking action of crospovidone, while the tablet disintegration is
facilitated by the swelling force exhibited by croscarmellose sodium.
WHAT ARE DISINTEGRANTS?
Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the
breakup of the tablet (and capsule “slugs’) into smaller fragments in an aqueous environment
thereby increasing the available surface area and promoting a more rapid release of the drug
substance.
There are three major mechanisms and factors affecting tablet disintegration as follows:
A: Swelling:
Although not all effective disintegrants swell in contact with water, swelling is believed to be a
mechanism in which certain disintegrating agents (such as starch) impart the disintegrating
effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is
overcome causing the tablet to fall apart.
B: Porosity and Capillary Action (Wicking):
Effective disintegrants that do not swell are believed to impart their disintegrating action through
porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into
tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to
enhance porosity and provide these pathways into the tablet. Liquid is drawn up or “wicked” into
these pathways through capillary action and rupture the interparticulate bonds causing the tablet
to break apart.
C: Deformation:
Starch grains are generally thought to be “elastic” in nature meaning that grains that are
deformed under pressure will return to their original shape when that pressure is removed. But,
with the compression forces involved in tableting, these grains are believed to be deformed
more permanently and are said to be “energy rich” with this energy being released upon
exposure to water. In other words, the ability for starch to swell is higher in “energy rich” starch
grains than it is for starch grains that have not been deformed under pressure.
It is believed that no single mechanism is responsible for the action of most disintegrants. But
rather, it is more likely the result of inter-relationships between these major mechanisms.
The classical example of the earliest known disintegrant is Starch. Corn Starch or Potato Starch
was recognized as being the ingredient in tablet formulations responsible for disintegration as
early as 1906 (even though tablet disintegration was itself not given much importance in tablet
formulations until much later).
Until fairly recently, starch was the only excipient used as a disintegrant. To be effective, corn
starch has to be used in concentrations of between 5-10%. Below 5%, there is insufficient
“channels” available for wicking (and subsequent swelling) to take place. Above 10%, the
incompressibility of starch makes it difficult to compress tablets of sufficient hardness.
Although the connection between bioavailability of drug and tablet disintegration took some time
to become appreciated, it is now accepted that the role of the disintegrant is extremely
important.
Other factors which affect the dissolution of Drugs from tablets are:
Type and Concentration of Active Ingredient
Type and Concentration of Binder Used
Type and Concentration of Fillers Used (soluble vs. insoluble)
Type and Concentration of Lubricant Used
Type of Dissolution testing Used (Apparatus, Speed, Media)
Manufacturing Process (wet granulation vs. compaction vs. direct compression)
In a direct compression process, drug is blended with a variety of excipients, subsequently
lubricated and directly compressed into a tablet. A disintegrant used in this type of formulation,
simply has to break the tablet apart to expose the drug substance for dissolution.
In a wet granulation process, the drug substance is combined with other excipients and
processed with the use of a solvent (aqueous or organic) with subsequent drying and milling to
produce granules. The resulting granules are then blended with additional excipients prior to
being compressed into a tablet. {Dry compaction is similar. But compression and milling are
used (rather than solvents) to make the granules}
A disintegrant used in granulated formulation processes can be more effective if used both
“intragranularly” and “extragranularly” thereby acting to break the tablet up into granules and
having the granules further disintegrate to release the drug substance into solution. However,
the portion of disintegrant added intragranularly (in wet granulation processes) is usually not as
effective as that added extragranularly due to the fact that it is exposed to wetting and drying
(as part of the granulation process) which reduces the activity of the disintegrant. Since a
compaction process does not involve its exposure to wetting and drying, the disintegrant used
intragranularly tends to retain good disintegration activity.
In addition to starch, the following are some of the disintegrants which were available prior to
the use of the “super-disintegrants” to be discussed later:
Pregelatinized Starch (Starch 1500)
Pregelatinized starch is a directly compressible form of starch consisting of intact and partially
hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a
binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 5-
10%. It’s major mechanism of action as a disintegrant is thought to be through swelling.
Microcrystalline Cellulose (Avicel)
Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because of
its excellent flow and binding properties. It is also an effective tablet disintegrant when used in a
concentration of between 10-20%.
Others
Sodium Bicarbonate in combination with citric or tartaric acids is used as an “effervescent”
disintegrant.
Alginic Acid at a concentration of between 5-10% is an effective, but very expensive
disintegrant.
Ion Exchange Resins (Amberlite 88) has disintegrant properties at a concentration of between
1-5%. But this type of disintegrant is rarely used.
SUPER DISINTEGRANTS:
Because of the increased demands for faster dissolution requirements, there are now available,
a new generation of “Super Disintegrants” in addition to the disintegrants discussed earlier.
Three major groups of compounds have been developed which swell to many times their
original size when placed in water while producing minimal viscosity effects:
1. Modified Starches- Sodium Carboxymethyl Starch (Chemically treated Potato Starch)
i.e. Sodium Starch Glycolate (Explotab, Primogel)
Mechanism of Action: Rapid and extensive swelling with minimal gelling.
Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to
gelling and its subsequent viscosity producing effects.
2. Cross-linked polyvinylpyrrolidone- water insoluble and strongly hydrophilic.
i.e. crospovidone (Polyplasdone XL, Kollidon CL)
Mechanism of Action: Water wicking, swelling and possibly some deformation recovery.
Effective Concentration: 2-4%
3. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose.
i.e. Ac-Di-Sol (Accelerates Dissolution), Nymcel
Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling.
Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation)
ADVANTAGES:
Effective in lower concentrations than starch
Less effect on compressibility and flow ability
More effective intragranularly
DISADVANTAGES:
More hygroscopic (may be a problem with moisture sensitive drugs)
Some are anionic and may cause some slight in-vitro binding with cationic drugs
(not a problem in-vivo.)
BINDER USED in WET GRANULATION
• Binder can be a sugar and polymer.
• Natural polymers binder: starch, gum (Acacia, tragacanth, gelatin)
• Synthetic polymers binder: PVP, methylcellulose, ethylcellulosa, hidroxypropylcellulosa\
• Can be used in dry or wet granulation. Wet method requires less material.\
• The amount of binder solution required for the 3 kg of filler are listed in the table
1. Starch (Amylum)
• Can be used as a filler, binder, and the disintegrant
• In the form of starch amili 5-10%
• Preparation :suspend starch 1:1 / 2-1 in cold water, add boiling water 2-4 times with constant
stirring until the starch that can expand into a transparent diluted
• Another way: a suspension of starch in water heated
• Contains 11-14% water content, will cause the tablet disintegrated quickly - The making must
be careful in order to obtain a good starch, is not hydrolyzed, and not making
• Best Use of a maximum of 30%. If a large dose of active ingredient, starch was replaced with a
better disintegrant, namely Avicel.
• Tablets containing a high concentration of starch tablets showed a fragile and difficult to be
dried
• Unmodified starch does not have good compressibility properties and have a great friability,
and the occurrence of capping in tablets if used in large quantities
As disintegrant:
• Usage: 1-20%, is the most commonly used disintegrant
• Mechanism of action by forming hydrogen bonds during compression and rupture or expand
when water entered Mell pore (capillary)
• Use is tailored to the type of starch, compression pressure, and water content of the mass
• Caution: C to remove absorbedbefore use, starch must be dried at a temperature of 80-90
water
2. Starch 1500
• Can be used as a binder in wet & dry granulation, and disintegrant
• Starch 1500 containing 20% maximum water-soluble fraction that functions as a binder while
the rest are as disintegrant
• Starch 1500 takes ± 3-4 times as much starch amylum to produce tablets with the same
hardness
• Should not be used as a filler in wet granulation because it will produce a gel that serves as a
powerful binder
• As disintegrant, can be added in dry state, in the outer phase.
• The good flow is directly compressible starch
• Can be compressed own, but if mixed with 5-10% of drugs requires additional lubricant (eg,
0.25% colloidal silicon dioxide)
• Containing 10% moisture and cause the tablets become soft when combined with magnesium
stearate> 0.5%, stearic acid used as a substitute
As disintegrant:
• Represents good disintegrant and added to the dry mixture (in inner phase or outer phase in
dry granulation or direct compression, or in the external phase on the wet granulation method)
• Caution: should not be given to the wet mass
3. Pregelatinized Starch
• It is a starch that has been cooked and dried again. Can be used as a substitute for starch
paste is more easily soluble in warm water without heating
• Can be added to dry into a powder and then moistened with water to form moist mass
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Labels: Artesunate and Amodiaquine Tablet Formulation, Binder, Excipients, Extended Release Formulations of
Metformin HCl 1000 mg by Wet Granulation
The Application of Starch 1500 (Pregelatinized
Starch) in Solid Dosage Form
Pregelatinized starches have been used for a long time in the food industry, so does in
Pharmaceutical industries. Starch 1500 is a unique pharmaceutical excipient combining several
properties in a single product.
Starch 1500 had multiple functions, such as binder, disintegrant, and flow-aid while having
lubricant properties. It is extremely versatile, being effective in a variety of processing methods
for solid oral dosage forms, such as direct compression, wet granulation, dry granulation/roller
compaction and encapsulation. Starch 1500 is particularly effective with moisture sensitive
actives and low dose applications and exhibits synergy, enhancing the functionality of other
commonly used excipients in formulations.
The Advantages of Pregelatinized Starch (Starch 1500)
Starch 1500 also has self-lubricating properties, which reduces the need for high levels of
lubricants, thus improving mechanical strength and dissolution of the product.
Pregelatinized starches had ability to thicken or gel promptly without the application of a
substantial amount of heat necessary with normal starches. However, this ability to rapidly
thicken or gel creates problems when these materials are used in dry products to be
reconstituted in small portions by the ultimate consumer.
DISINTEGRANT USED IN WET GRANULATION
Function: to split tablets
How to use: - when granulation
- Before compressing (the best)
1. Starch (Amylum)
2. Starch 1500
3. Sodium starch glycolate (primogel, explotab)
• Usage: 1-20% with optimum concentration : 4%
• Explotab can not be use as disintegrant in inner phase
• Mechanism similar to starch in general, is a modified starch that can absorb water 200-300%
• Disintegration time is determined also by the amount of compression pressure
• Attention: at high temperature and high humidity can prolong disintegration time, slowing down
the dissolution time
4. Cellulose (cellulose, methylcellulose, CMC, CMC-Na, Avicel, Acdisol)
• Acdisol is crosslinking of CMC-Na and excellent for use as disintegrant because water soluble
and has a great affinity to water.
• Acdisol is listed on the super disintegrant. Usage: 2-5%.
The Important Parameter in Tablet Coating Process
Parameters Influences in Tablet Coating Process
Tablet coating is a complex process that is affected by many variables. Some of those variables
can be evaluated or controlled, others can’t.
Here are some of the parameters you should check when evaluating coating process to
determine the source of defective coated tablets.
1. Control. Many problems occur in coating when you can’t control every important parameter,
such as temperature, pan pressure, spray rates, and atomization pressure. But, the tablet’s
surface temperature can be measure with additional tools (out from the coating equipment) by
using infra red thermometer (laser thermometer).
2. Tablet quality. Tablets must have the proper porosity, surface, hardness, and moisture
content. You can’t have consistent coating without consistent tablet quality.
3. Waiting period. Most tablets cannot be coated immediately after they’ve been compressed.
The energy within the tablets is still fairly high and they are still warm. In addition, tablet
hardness changes over 24 to 48 hours. Let the tablets rest at least that long before you coat
them meanwhile you can check the uncoated tablet for assay, dissolution or other specification
by quality control. After the QC released the tablet, then you can start the coating process.
