Quality control of suppositories

I. Uniformity of weight (weight Variation) (B.P. 1980):

1. Weigh 20 suppositories individually. w1, w2, w3….w20
2. Weigh all the suppositories together = W.
3. Calculate the average weight = W/20.
4. Limit: not more than 2 suppositories differ from the average weight by more than
5%, and no suppository differs from the average weight by more than 10%.
5 * avg.wt.
 Upper limit = average weight +
100
5 * avg.wt.
 Lower limit = average weight -
100
Not more than two of the suppositories differ from the average weight by more than the %
error listed. If more than two suppositories are different from the average weight by 5%,
calculate double the percent error as follows:

10 * avg.wt.
 Upper limit = average weight +
100
10 * avg.wt.
 Upper limit = average weight -
100
1. No suppository differs by more than double that percentage.

II. Hardness of Suppositories (Breaking Test)

1. The suppository is placed in the instrument.
2. Add 600 g; leave it for one min. (use a stop watch).
3. If not broken, add 200 g every one min. until the suppository is broken.
Calculations:

The hardness of the suppository is calculated by adding the weights together. But if
the suppository is broken before the end of the last min. the last weight is canceled.
 Results:

 Using polyethylene suppositories  H = 1.7 kg.

 Using Indocid suppositories _ H = 4 kg.
 Using Glycerin suppositories  H = 1.4 kg.

III. Melting Range Test:

 This test is also called the Macromelting range test and is a measure of the time it
takes for the entire suppository to melt when immersed in a constant-temperature
(37oC) water bath.
 The apparatus commonly used for measuring the melting range of the entire
suppository is the USP Tablet Disintegration Apparatus.
Procedure:

The suppository is completely immersed in the constant temperature water bath, and the
time for the entire suppository to melt or disperse in the surrounding water is measured.

The suppository is considered disintegrated when:

2. It is completely dissolved or
3. Dispersed into its component part.
4. Become soft “change in shape” with formation of core which is not resistant to
pressure with glass rod.

Disintegration test for suppositories (WHO Procedure)

The disintegration test determines whether suppositories soften or disintegrate within a
prescribed time when placed in an immersion fluid using the experimental conditions
described below.

Disintegration is considered to be achieved when:

- dissolution is complete;

- the components of the suppositories have separated, e.g. melted fatty substances have
collected on the surface of the liquid, insoluble powders have fallen to the bottom, and
soluble components have dissolved or are distributed in one or more of the ways described
in Methods 1 and 2;

- there is softening of the test sample, usually accompanied by an appreciable change of

shape without complete separation of the components. The softening process is such that a
solid core no longer exists when pressure is applied with a glass rod; or

- rupture of the gelatin shell or rectal capsule occurs resulting in release of the contents.

Method 1 (for water-soluble, hydrodispersible and fat-based suppositories):

This test measures the time elapsed for a suppository placed in water to disintegrate.

Apparatus

The apparatus (Fig. 1) consists of a 60-mm long cylinder of glass or transparent plastic and
a metal device consisting of two perforated stainless steel discs, held about 30 mm apart.
These discs each have 39 holes, 4mm in diameter, which are evenly spaced in a concentric
pattern. The diameter of the discs is marginally inferior to that of the interior of the
cylinder. Once inserted into the cylinder, the metal device is attached to the rim of the
cylinder by means of three spring clips. The test is carried out using three such
apparatuses, each containing a single test sample. Each apparatus is placed in a beaker with
a minimum capacity of 4 litres filled with water unless otherwise prescribed. The beaker is
fitted with a slow stirrer and a support that holds the apparatus vertically 90 mm below
the surface of the water so that it can be inverted without emerging from the water.
Figure 1. Apparatus for water-soluble, hydrodispersible, and fat-based suppositories
A. Horizontal view

B. Vertical view

Measurements in mm.

British Pharmacopoeia, 1999, Crown copyright material. Reproduced with the permission
of the Controller of Her Majesty's Stationery Office.

Recommended procedure

Unless otherwise described in the individual monograph, use water maintained at a

temperature of 36-37°C as the immersion fluid. The test requires three suppositories and
the procedure is applied to each of the suppositories.

Place the sample on the lower disc of the metal device and then insert it into the cylinder.
Place the apparatus into the beaker and invert it every 10 minutes without removing it
from the liquid. Repeat the operation with the remaining two suppositories. Record the
time required for the disintegration of the suppositories.

Unless otherwise stated in the individual monograph, for each of the three suppositories,
examine the state of the sample after 30 minutes for fat-based suppositories and rectal
capsules, and after 60 minutes for water-soluble suppositories.
Method 2 (alternative for fat-based suppositories):

This test measures the time elapsed for a suppository placed in water to soften to the
extent that it no longer offers resistance when a defined weight is applied.

Apparatus

The apparatus (Fig. 2) consists of a flat-bottomed glass tube about 140mm long with an
internal diameter of 15.5 mm and a two-part rod. The tube is closed with a removable
plastic cover that has an opening 5.2mm in diameter. The rod has two parts: both made of
plastic, or the lower part made of plastic and the upper of metal. The rod is 5 mm in
diameter and widens at the lower end to a diameter of 12mm. To the bottom of the lower
end is fixed a metal needle 2mm long and 1mm in diameter. The upper part of the rod has
an adjustable sliding ring and a weighted disc is attached to the top. The two parts are held
tightly together for the manual version or separated for the automatic version. The weight
of the entire rod should be 30 g ± 0.1 g.

Recommended procedure

Unless otherwise described in the individual monograph, use water maintained at a

temperature of 36-37°C as the immersion fluid. The test requires three suppositories and
the procedure is applied to each of the suppositories.

Figure 2. Alternative apparatus for fat-based suppositories

Measurements in mm.
Reproduced with the permission of the European Pharmacopoeia Commission, European
Directorate for the Quality of Medicines, Council of Europe.

Place the glass tube containing 10 ml of water in the water-bath and equilibrate at 36.5 ±
0.5 °C. Fix the glass tubes vertically and immerse to a depth of at least 7 cm below the
surface but without touching the bottom of the waterbath. Introduce a suppository, tip
first, into the tube followed by the rod with the free gliding plastic cover into the glass tube
until the metal needle touches the flat end of the suppository. Put the cover on the tube.
Note the time which elapses until the rod sinks down to the bottom of the glass tube and
the mark ring reaches the upper level of the plastic cover.

Each of the three suppositories should melt within 30 minutes, unless otherwise stated in
the individual monograph.

Quality control of suppositories (Cont.)

1. Appearance:
This includes odour, colour, surface condition and shape.

2. Weight Uniformity:

- Weigh 20 suppositories individually. w1, w2, w3….w20

- Weigh all the suppositories together = W.
- Calculate the average weight = W/20.
Limit: Not more than 2 suppositories differ from the average weight by more than 5%, and
no suppository differs from the average weight by more than 10%.

3. Melting range test:

- Determines the time taken by an entire suppository to melt when it is immersed in a

constant temperature bath at 37°C.
-The experiment done by using the USP Tablet Disintegration Apparatus.

Procedure:
1-The suppository is completely immersed in the constant temperature water bath, and the
time for the entire suppository to melt or disperse in the surrounding water is measured.
- The suppository is considered disintegrated when:
A- It is completely dissolved or
B- Dispersed into its component part.
C- Become soft “change in shape” with formation of core which is not resistant to pressure
with glass rod.
 4. Liquefaction Time or Softening Time Test:

- In this test a U tube is partially immersed in a constant temperature bath and is

maintained at a temperature between 35 to 37°C. There is a constriction in the tube in
which the suppository is kept and above the suppository, a glass rod is kept. The time taken
for the glass rod to go through the suppository and reach the constriction is known as the
liquefaction time or softening time. - Another apparatus is there for finding “softening
time” which mimics in vivo conditions. It uses a cellophane tube, and the temperature is
maintained by water circulation. Time taken for the suppository to melt is noted.

5. Breaking Test (Hardness):

- The breaking test is designed as a method for measuring the fragility or brittleness of
suppository.
1-The suppository is placed in the instrument.
2- Add 600 g; leave it for one min. (use a stop watch).
3- If not broken, add 200 g every one min. until the suppository is broken.

Calculations:

 The hardness of the suppository is calculated by adding the weights together.

 But if the suppository is broken before the end of the last min. the last weight is
canceled.

6. Dissolution test:
By using different types of apparatus such as wire mesh basket, or dialysis tubing is used to
test for in vitro release from suppositories.
 7. Stability testing:

-Cocoa butter suppositories on storage, “bloom”; i.e., they form a white powdery deposit on
the surface. This can be avoided by storing the suppositories at uniform cool temperatures
and by wrapping them in foils.
- Fat based suppositories harden on storage, i.e., there is an upward shift in melting range
due to slow crystallization to the more stable polymorphic forms of the base.
- The softening time test and differential scanning calorimetry can be used as stability
indicating test methods.
- If we store the suppositories at an elevated temperature, just below its melting range,
immediately after manufacture, the aging process is speeded up.