Shenyang Pharmaceutical University LAB 4: TABLETS PHARMACEUTICS I

LABORATORY 4: Preparation of tablets and factors

influencing tablets qualities

1. LABORATORY OBJECTIVES
a) To learn the preparation method of tablets by wet granulation.
b) To learn how to use a single punch tableting machine.
c) To know the evaluation methods for tablets.
d) To investigate the influence of compression pressure and types of disintegrants on
the hardness and disintegration time of tablets.

2. INTRODUCTION
Tablet is an important solid dosage form which is usually prepared with the aid of
suitable pharmaceutical excipients. Tablets may vary in size, shape, weight, hardness,
thickness, disintegration and dissolution characteristics and in other aspects, depending on
their intended use and method of manufacture.
Compressed tablets may be manufactured by three basic methods: wet granulation,
dry granulation, and direct compression. Wet granulation is a widely used method for the
production of compressed tablets. The steps are (a) weighing and blending of the
ingredients, (b) preparing a damp mass, (c) converting the damp mass into wet granules,
(d) drying the granules, (e) sizing the granules by dry screening, (f) adding lubricant and
blending, and (g) forming tablets by compression. Figure 1 is the schematic description of
the wet granulation method.
During the preparation process, each step may influence the quality of tablets
produced. Prior to processing, all the active ingredients and excipients must be dried,
milled, and sieved (80-100 mesh). Specified amounts of active ingredients, fillers, and
disintegrating agents are mixed by means of a powder blender or mixer until a
homogeneous mixture is formed. A liquid binder is subsequently added to the powder
mixture to facilitate agglomeration of the powder particles. A damp mass resembling a
dough is formed and further processed into granules. The amount of binding agent added is
usually determined by the operator based on the observation that the binder-powder
mixture forms a compact wet mass when being squeezed in the hands. However, care must
be exercised not to over-wet or under-wet the power. Over-wetting can result in granules
that are too hard for proper tablet formation and under-wetting can result in tablets that are
soft and prone to crumbling. The wet mass is forced through a screen to form wet granules.
This may be done by hand or with a granulation equipment which is used to prepare
granules by extruding the wet mass through a screen as part of the equipment. The
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Shenyang Pharmaceutical University LAB 4: TABLETS PHARMACEUTICS I

resultant wet granules are spread evenly on a large piece of paper in a shallow tray for
drying. Granules may be dried in a thermostatically controlled oven with the monitoring of
time, temperature, and humidity.

adjuvants Liquid binder

Drug Grind Sieve Blend Damp mass

Lubricants, disintegrants

Pellets/granule Dry Screen Weigh

s orgranulation

Blend Compress Tablet

Figure 1. Process of tablets preparation by the wet granulation method.

After drying, the granules are forced through a screen of a smaller mesh size than that used
to prepare the wet granulation. The degree to which the dried granules are reduced depends
on the size of the punch to be used for tablet compression. In general, the smaller the tablet
to be produced, the smaller the granules should be prepared as shown in Table 1. Screens
of 10 to 20 mesh size are generally used for this purpose. After dry screening, a lubricant
(sometime with a portion of the disintegrant) is added to the dried granules through a fine-
mesh screen, followed by proper powder mixing. It is essential to measure the drug content
in the final granules before tableting in order to calculate the weight of the tablet using the
following equation:
drug amount in each tablet the label claim
Tablet weight
the measured drug content in the mixture
Unless otherwise stated in the monograph of CP, the requirements for content
uniformity should be met if the amount of active ingredients in each dosage unit lies within
the range of 90% to 110% of the label claim.
The screen size and punch diameter can be selected based on the tablet weight
according to Table 1. However, the parameters should be adjusted with the change of drug
density.
In addition to the appearance, tablets must meet other physical specifications and
quality standards, including the criteria for weight variation, content uniformity, thickness,
hardness, disintegration, and dissolution. In-process controls must be performed during
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Shenyang Pharmaceutical University LAB 4: TABLETS PHARMACEUTICS I

production and these criteria must be verified after the production of a batch to ensure that
established product quality standards are met. Furthermore, the hardness and disintegration
time of tablets will be affected by the type and concentration of disintegrants and lubricants
added and the compression pressure applied during tablet preparation.

Table 1. The relationship among tablet weight, screen size, and punch diameter
Tablet weight (mg) Screen size for wet Screen size for Punch diameter
granulation sizing (mm)
50 18 16-20 5-5.5
100 16 14-20 6-6.5
150 16 14-20 7-8
200 14 12-16 8-8.5
300 12 10-16 9-10.5
500 10 10-12 12

3. METHODS
3.1 Influence of compression pressure on the hardness and disintegration time of
aspirin tablets
3.1.1 Formulation:
Aspirin (acetylsalicylic acid) 20 g
Starch 2g
Citric acid q.s.
10% starch mucilage q.s.
Talc 1g

3.1.2 Procedures
a) Preparation of 10% starch mucilage: Dissolve 0.2 g of citric acid in 20 mL of
distilled water followed by adding and dispersing 2 g of starch. The final mixture is
heated on a water bath until the starch is gelatinized giving rise to mucilage.
b) Granulation: Mix the specified amount of aspirin and starch until uniform using the
geometric dilution method. A damp mass of this powder mixture is prepared by
adding appropriate amount of the 10% starch mucilage and kneading by hand. The
wet mass is subsequently forced through a 16-mesh screen to form the wet granules.
The resultant granules are spread evenly on a large piece of paper in a tray and dried
at 40-60oC in an oven. After drying, the granules are passed through a 16-mesh
screen and mixed with 5% talc.
c) Tableting under different pressures Using the aspirin granules prepared above,
tablets are prepared under a high and a low compression pressure. Measure the

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hardness and disintegration time of the tablets and record the results in Table 3.

3.1.3 Notes
a) Aspirin will be discolored (red) upon the contact with ironware particularly in the
presence of moisture. Therefore, ironware should not be used during the
preparation process. Nylon screens and stainless steel containers should be used
instead. Fast drying is advised but the drying temperature should not be too high to
avoid accelerating the hydrolysis of aspirin.
b) Preparation of the starch mucilageEither direct heating or water bath can be used.
When using direct heating, it is important to stir continuously to avoid over-heating
or burning.
c) Temperature of the mucilage: After preparation, the mucilage should be cooled
down before adding to the aspirin powder mixture. If it is too hot, the high
temperature will cause degradation of Aspirin. If it is cooled down too much, it
may be too thick and make the wet granulation process (kneading) difficult.

3.2 Influence of the types of disintegrants and surfactants on the disintegration time
of acetaminophen tablets
3.2.1 Formulation:
Acetaminophen 20 g
15% starch mucilage q.s.
Disintegrant q.s.
Magnesium stearate q.s.

3.2.2 Procedures
a) Preparation of a Starch-Tween mixture Dissolve 0.5g of Tween-80 in 15mL of
ethanol, add the solution to 15g of starch, and mix until uniform. Dry the mixture at
70 and then pass the dry mixture through a 100-mesh screen.
b) Preparation of 15% starch mucilage 6g starch is dispersed in 40mL of distilled
water and gelatinized using a water bath.
c) Preparation of acetaminophen granules Weigh 20g of acetaminophen and add
appropriate amount of 15% starch mucilage to prepare the damp mass. The wet
mass is subsequently forced through a 16-mesh screen by hand to give rise to wet
granules. The resultant granules are spread evenly on a large piece of paper in a tray
and dried at 60 in an oven. After drying, the granules are passed through a 16-
mesh screen.
d) Addition of different types of disintegrants or surfactants: The dried acetaminophen
granules (c) were divided into three equal portions. Add 6% dry starch, 6% sodium
carboxymethyl starch (CMS-Na) and 6% Tween-starch to each portion respectively.
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Add 1% magnesium stearate to the each mixture and mix until uniform. These three
granulations are subsequently tableted using the same compression pressure and the
disintegration times of the tablets are measured.

3.2.3 Notes
Dry starch: Starch should be dried for 2 hours at 105 and the water content should
be less than 8%.

3.3 Influence of hydrophobic lubricants on the disintegration time of sodium

bicarbonate tablets
3.3.1 Formulation:
Sodium bicarbonate 20 g
Starch 2g
10% Starch mucilage q.s.
Magensium stearate q.s.

3.3.2 Procedures
a) Preparation of 10% starch mucilage 2g starch is dispersed uniformly in 20mL of
distilled water and gelatinized using a water bath.
b) Preparation of sodium bicarbonate granules Mix 20g of sodium bicarbonate and
2g of starch until uniform using the geometric dilution method. Prepare the damp
mass by adding appropriate amount of 10% starch mucilage. The wet mass is forced
through a 16-mesh screen by hand to prepare the wet granules. The resultant
granules are dried at 50 in an oven. After drying, the granules are passed through
a 16-mesh screen.
c) Adding different percents of hydrophobic lubricants: Divide the dried sodium
bicarbonate granules (b) into two equal portions. Add 0.6% and 3% magnesium
stearate to each portion respectively and mix until uniform. The granules are
compressed under the same pressure. Measure the disintegration time of the tablets.

3.4 Preparation of Vitamin C tablets

3.4.1 Formulation:
Vitamin C 50.0 g
Starch 20.0 g
Dextrin 30.0 g
Tartaric acid 1.0 g
50% alcohol q.s.
Magnesium stearate 1.0 g

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3.4.2Procedures
Mix a specified amount of Vitamin C, starch, and dextrin until uniform using the
geometric dilution method. Dissolve tartaric acid in an appropriate amount of 50% alcohol
and add to the powder mixture to prepare the damp mass by hand kneading. The wet mass
is forced through a 18~20 mesh screen to prepare the wet granules. The resultant granules
are dried at 60 and the final water content of the dry granules should be less than 1.5%.
After drying, the granules are passed through a screen of 18~20 mesh. The fine powder in
the granules (separated by sieving) is first mixed with the specified amount of magnesium
stearate, and then combines with the dry granules prior to tableting.

3.4.3 Notes
a) Vitamin C will decompose and change its color in the presence of moisture,
especially upon the contact with metals such as copper and iron. To avoid this from
happening, the granulation process should be fast and the granules should be dried
below 60.
b) In the formulation, tartaric acid is used as a chelating agent which can prohibit the
discoloration of vitamin C upon the contact with metal ions. Similarly, 2% citric acid
can be used as a chelating agent. Due to the small amount of tartaric acid in the
formulation, it should be dissolved in 50% alcohol before adding to the powder to
ensure its uniform distribution.

3.5 Quality test and evaluation

Tablet hardness, friability, disintegration and weight variation should be tested using
the methods described in the attachment 1 and results should be recorded in Table 2 and
Table 3.

4. RESULTS AND DISCUSSION

4.1 Record the results in Table 2 and 3.

Table 2. Influence of compression pressure on the hardness

and disintegration time of tablets
Hardness (kg) Disintegration time (min)
No Pressure
1 2 3 4 5 6 average 1 2 3 4 5 6 average
1 High
2 Low
Conclusion

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Shenyang Pharmaceutical University LAB 4: TABLETS PHARMACEUTICS I

Table 3. Influence of types of disintegrants and surfactants

on the disintegration time of tablets
No Hardness (kg) Disintegration time (min)

1 2 3 4 5 6 average 1 2 3 4 5 6 average

3 6% dry starch
4 6% CMS-Na
5 6% Tween-starch
6 Vitamin C tablet
7 Compound liquorice tablet

4.2 Based on the experimental results, summarize the factors influencing tablet
disintegration time and the possible disintegration mechanism.
4.3 Based on the experimental results, summarize the relationship between the properties
of the active ingredient and the selection of excipients.

5. QUESTIONS
a) How to avoid the hydrolysis of aspirin during tablet preparation? What type of
lubricants should be selected?
b) If tablets disintegrate within the prescribed time, is it necessary to determine the
dissolution rate?
c) What is the difference between the preparation method for traditional Chinese
extract tablets and tablets of chemical drugs?

Attachment 1
All the following parameters should be tested according to CP 2005.
1. Hardness test
A tablet should possess some degree of mechanical strength to withstand the
mechanical shocks caused by handling during manufacturing, packaging, shipping, and
dispensing.
The main principle of hardness measurement of a tablet involves subjecting the tablet
to an increasing load until the tablet breaks or fractures. A method of testing the hardness
of a circular tablet is performed by placing the tablet on its edge in a vertical position
between the two tablet holding plates (jaws) of the hardness tester. A controlled pressure is
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applied to the tablet by one plate and transmitted to the other plate which is connected to a
pressure gauge. The maximum pressure is recorded when the tablet breaks. Oral tablets
normally have a hardness of 4 to 10 kg; however, hypodermic and chewable tablets are
much softer (3 kg) and some sustained release tablets are much harder (10-20 kg).

2. Tablet friability
This test is performed to determine, under defined testing conditions, the friability of
uncoated tablets, which is extent of damage of the tablet surfaces, lamination or
fragmentation caused by the impact of falling and attrition between tablets. Commercially
available apparatuses known as friability testers are used for the test. Basically, it consists
of a drum with a diameter between 283 mm and 291mm and a width of 36 mm40 mm and
is made of transparent plastic material (Fig. 1). The drum is attached to the horizontal axis
of a rotating device that rotates at 25 1 rpm. The tablets are tumbled at each turn of the
drum by following a curve projection with an inside radius of 75.5 mm85.5 mm that
extends from middle of the drum to the outer wall. Thus, at each turn, the tablets roll or
slide and fall onto the drum wall or onto each other. Usually, a sample of 10 tablets are
tested at a time, unless the tablet weight is 0.65 g or less, where 20 tablets are tested. The
tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample
and place the tablets in the drum. After 100 turns, remove any loose dust from the tablets
and reweigh the tablet sample. If the reduction in the total mass of the tablets is more than
0.8% (1% in USP), the tablet sample fails the friability test. Generally, the test is done
once. If cracking, capping, or fragmentation of the tablets is observed, the sample also fails
the test.

Fig. 1 Schematic of a friability Fig. 2 Schematic of a tablet

testing apparatus. disintegration apparatus.

3. Disintegration test
A disintegration test is performed to determine how fast a tablet disintegrates into
aggregates and/or finer particles. This test allows the determination of whether the tablets
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disintegrate within the prescribed time when placed in a liquid medium under the
experimental conditions. However, disintegration does not imply complete dissolution of
the active ingredient(s) from the tablet. Complete disintegration is defined as the state in
which any residue of the unit, except fragments of insoluble coating or capsule shell,
remaining on the screen of the test apparatus or adhering to the lower surface of the disk, if
used, is a soft mass having no palpably firm core.
The basket-rack assembly method: The apparatus consists of a basket-rack assembly,
a 1000-mL beaker for the immersion fluid, an heating element for thermostatic heating of
the fluid between 35 and 39C, and a device for raising and lowering the basket in the
immersion fluid at a constant frequency rate between 29 and 32 cycles per minute through
a distance of not less than 53 mm and not more than 57 mm (Figure 2). The volume of the
fluid in the vessel is kept at a level that at the highest point of the upward stroke the wire
mesh remains at least 15 mm below the surface of the fluid and descends to not less than
25 mm from the bottom of the vessel on the downward stroke. At no time should the top of
the basket-rack assembly become submerged. The time required for the upward stroke is
equal to the time required for the downward stroke and the change in stroke direction is a
smooth transition, rather than an abrupt reversal of motion. The basket-rack assembly
moves vertically along its axis. There is no appreciable horizontal motion or movement of
the axis away from the vertical position.
The basket-rack assembly consists of six open-ended transparent tubes, each 77.5 2.5
mm long and having an inside diameter of 20.7 to 23 mm and a wall 1.0 to 2.8 mm thick;
the tubes are held in a vertical position by two plates, each 88 to 92 mm in diameter and 5
to 8.5 mm in thickness, with six holes, each 22 to 26 mm in diameter, equidistant from the
center of the plate and equally spaced from one another. Attached to the under surface of
the lower plate is a woven stainless steel wire cloth, which has a plain square weave with
1.8- to 2.2mm apertures and with a wire diameter of 0.57 to 0.66 mm.
Place 1 tablet in each of the six tubes of the basket, and operate the apparatus, using
water maintained at 37 1C as the immersion fluid. At the end of the time limit specified
(15min. for uncoated tablets), lift the basket from the fluid and observe the tablets to see
whether all of the tablets have disintegrated completely. If 1 or 2 tablets fail to disintegrate
completely, repeat the test on 12 additional tablets. The requirement is met if not less than
16 of the total of 18 tablets tested pass the test.
Although this test is prescribed for some products in the pharmacopeias, its use is
generally diminishing in favor of drug dissolution testing.

4. Weight variation
Weigh individually 20 tablets and calculate the average weight. The requirements are
met if the weights of not more than 2 of the tablets differ from the average weight by more
than the percentage listed in Table 4 and no tablet differs in weight by more than double
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that percentage.

Table 4. Weight variation tolerance for uncoated tablets

Average weight of tablets Percentage difference
Less than 0.30g 7.5%
0.30g or more than 0.30g 5%

References
[1] H. C. Ansel, N. G. Popovich and L. V.Allen, Jr. Pharmaceutical Dosage Forms and
Drug Delivery Systems, , 8th ed., Williams and Wilkins, Baltimore, 2005.
[2] M.E. Aulton. Pharmaceutics: The science of dosage form design. 1988.

(Shirui MAO)

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