2.9.23. Gas pycnometric density of solids EUROPEAN PHARMACOPOEIA 11.

APPARATUS A 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.
APPARATUS B
The apparatus (see Figure 2.9.22.-2) consists of a
water-bath (B) into which an inner tube (A) is inserted and
fixed with a stopper. The inner tube is closed by a stopper
at the bottom. The apparatus is fitted with a thermometer.
2 insets are available :
– a glass rod (C1) in the form of a tube sealed at both ends,
carrying a rim at its lower end weighed with lead shot,
which has a weight of 30 ± 0.4 g,
– a penetration inset (C2) consisting of a rod (7.5 ± 0.1 g) in
a tube which has an enlargement for the suppository, both
made of stainless steel.
Method. Pour 5 mL of water at 36.5 ± 0.5 °C into the inner
tube (A), introduce a suppository with the tip downwards and
onto that, place the inset (C1 or C2). Note the time which
elapses between this moment and the moment when the
lower, rimmed end of the glass rod (C1) or the steel rod (C2)
reaches the narrowed part of the inner glass tube. Melting or
dissolution is then considered as complete.

Figure 2.9.22.-1. – Apparatus A for measuring the softening

time of lipophilic suppositories
Dimensions in millimetres
The apparatus (see Figure 2.9.22.-1) consists of a glass tube
15.5 mm in internal diameter with a flat bottom and a length
of about 140 mm. The tube is closed by a removable plastic
cover having an opening 5.2 mm in diameter. The apparatus
comprises a rod 5.0 mm in diameter which becomes wider Figure 2.9.22.-2. – Apparatus B for measuring the softening
towards the lower end, reaching a diameter of 12 mm. A metal time of lipophilic suppositories
needle 2 mm in length and 1 mm in diameter is fixed on the Dimensions in millimetres
flat underside.
The rod consists of 2 parts, a lower part made of plastic
material and an upper part made of plastic material or metal 04/2019:20923
with a weight disk. The upper and lower parts are either fitted
together (manual version) or separate (automated version).
The weight of the entire rod is 30 ± 0.4 g. The upper part of the
rod carries a sliding mark ring. When the rod is introduced
into the glass tube so that it touches the bottom, the mark ring 2.9.23. GAS PYCNOMETRIC DENSITY
is adjusted to coincide with the upper level of the plastic cover.
Method. Place the glass tube containing 10 mL of water in a
OF SOLIDS(10)
water-bath and equilibrate at 36.5 ± 0.5 °C. Fix the glass tube Gas pycnometric density is determined by measuring the
vertically and immerse to a depth of at least 7 cm below the volume occupied by a known mass of powder, which is
surface but without touching the bottom of the water-bath. equivalent to the volume of gas displaced by the powder using
Introduce a suppository, tip first, into the tube followed by a gas displacement pycnometer. In gas pycnometric density
the rod with the free gliding plastic cover into the glass tube measurements, the volume determined excludes the volume
until the metal needle touches the flat end of the suppository. occupied by open pores ; however, it includes the volume
Put the cover on the tube (beginning of time measurement). occupied by sealed pores or pores inaccessible to the gas.
(10) This chapter has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

386 See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 11.0 2.9.25. Dissolution test for medicated chewing gums

Usually, helium is used as a test gas due to its high diffusivity under vacuum. Because volatiles may be evolved during the
into small open pores. If gases other than helium are used, measurement, weighing of the sample is carried out after the
different values would be obtained, since the penetration of pycnometric measurement of volume.
the gas is dependent on the size of the pore as well as the
cross-sectional area of the gas molecules. Weigh the test cell of the pycnometer and record the mass. Fill
the test cell with a given mass of powder of the substance to
The measured density is a volume-weighted average of the be examined. Seal the test cell in the pycnometer. Record the
densities of individual powder particles. It is called the particle system reference pressure (Pr) as indicated by the manometer
density, distinct from the true density of a solid or the bulk while the valve that connects the expansion cell with the test
density of a powder. The density of solids is expressed in grams cell is open. Close the valve to separate the expansion cell from
per cubic centimetre (g/cm3), although the International Unit the test cell. Pressurise the test cell with the gas to an initial
is the kilogram per cubic metre (1 g/cm3 = 1000 kg/m3). pressure (Pi) and record the value obtained. Open the valve to
connect the expansion cell with the test cell. Record the final
APPARATUS pressure (Pf). Repeat the measurement sequence for the same
The apparatus (see Figure 2.9.23.-1) consists of the following : powder sample until consecutive measurements of the sample
volume (Vs) agree to within 0.2 per cent. Unload the test cell
– a sealed test cell, with empty cell volume Vc, connected and measure the final powder mass (m), expressed in grams.
through a valve to an expansion cell, with volume Vr ; If the pycnometer differs in operation or construction from
– a system capable of pressurising the test cell with the the one shown in Figure 2.9.23.-1, follow the instructions of
measurement gas until a defined pressure (P) indicated by the manufacturer of the pycnometer.
a manometer ;
– the system is connected to a source of measurement gas, EXPRESSION OF THE RESULTS
preferably helium, unless another gas is specified. The sample volume (Vs) is given by the equation :
The gas pycnometric density measurement is performed at a
temperature between 15 °C and 30 °C that does not vary by Vr
Vs = Vc -
more than 2 °C during the course of measurement. Pi - Pr
-1
The apparatus is calibrated, which means that the volumes Vc Pf - Pr
and Vr are determined using a suitable calibration standard
whose volume is known to the nearest 0.001 cm3. The The density (ρ) is given by the equation :
procedure described below is followed in 2 runs, firstly with m
an empty test cell, and secondly with the calibration standard ρ=
placed in the test cell. The volumes Vc and Vr are calculated Vs
using the equation for the sample volume (Vs), taking into The sample conditioning is indicated with the results. For
account that Vs is zero in the first run. example, indicate whether the sample was tested as is or dried
under specific conditions such as those described for loss on
drying.

04/2012:20925

2.9.25. DISSOLUTION TEST FOR

MEDICATED CHEWING GUMS
PRINCIPLE
The test is used to determine the dissolution rate of active
substances in medicated chewing gums. This is done by
applying a mechanical kneading procedure to a piece of gum
placed in a small chamber designed to simulate the process
of chewing.
A = valve ;
Vr expansion volume, in cubic centimetres ; APPARATUS A
=
Vc cell volume, in cubic centimetres ; Chewing apparatus A (Figure 2.9.25.-1) consists of :
=
Vs sample volume, in cubic centimetres ; – 1 chewing chamber ;
=
M manometer. – 1 vertical piston ;
=
– 2 horizontal pistons with O-rings and sealing rings.
Figure 2.9.23.-1. – Schematic diagram of a gas pycnometer
The chewing chamber consists of 4 individual parts :
METHOD – 1 central chamber ;
Volatile contaminants in the powder are removed by degassing
– 1 funnel (Figure 2.9.25.-2);
the powder under a constant purge of helium prior to the
measurement. Occasionally, powders may have to be degassed – 2 guides with bushes (Figure 2.9.25.-3).

General Notices (1) apply to all monographs and other texts 387
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