CHEMICAL RESISTANCE—GLASS CONTAINERS
The following tests are designed to determine the resistance to water attack of
new (not previously used) glass containers. The degree of attack is determined
by the amount of alkali released from the glass under the influence of the
attacking medium under the conditions specified. This quantity of alkali is
extremely small in the case of the more resistant glasses, thus calling for
particular attention to all details of the tests and the use of apparatus of
high quality and precision. The tests should be conducted in an area relatively
free from fumes and excessive dust.
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Glass Types— Glass containers suitable for packaging Pharmacopeial preparations
may be classified as in Table 2 on the basis of the tests set forth in this
section. Containers of Type I borosilicate glass are generally used for
preparations that are intended for parenteral administration. Containers of Type
I glass, or of Type II glass (i.e., soda-lime glass that is suitably
dealkalized) are usually used for packaging acidic and neutral parenteral
preparations. Type I glass containers, or Type II glass containers (where
stability data demonstrate their suitability), are used for alkaline parenteral
preparations. Type III soda-lime glass containers usually are not used for
parenteral preparations, except where suitable stability test data indicate that
Type III glass is satisfactory for the parenteral preparations that are packaged
therein. Containers of Type NP glass are intended for packaging nonparenteral
articles, i.e., those intended for oral or topical use.
Table 2.Glass Types and Test Limits 
Apparatus—
Autoclave— For these tests, use an autoclave capable of maintaining a
temperature of 121 ± 2.0, equipped with a thermometer, a pressure gauge, a vent
cock, and a rack adequate to accommodate at least 12 test containers above the
water level.
Mortar and Pestle— Use a hardened-steel mortar and pestle, made according to the
specifications in the accompanying illustration.
Special Mortar and Pestle for Pulverizing Glass2
Other Equipment— Also required are 20.3-cm (8-inch) sieves made of stainless
steel including the Nos. 20, 40, and 50 sieves along with the pan and cover (see
Sizes of Standard Sieve Series in Range of Interest under Particle Size
Distribution Estimation by Analytical Sieving 786), 250-mL conical flasks made
of resistant glass aged as specified, a 900-g (2-lb) hammer, a permanent magnet,
a desiccator, and an adequate volumetric apparatus.
Reagents—
High-Purity Water— The water used in these tests has a conductivity at 25, as
measured in an in-line cell just prior to dispensing, of not greater than 0.15
µS per cm (6.67 Megohm-cm). There must also be an assurance that this water is
not contaminated by copper or its products (e.g., copper pipes, stills, or
receivers). The water may be prepared by passing distilled water through a
deionizer cartridge packed with a mixed bed of nuclear-grade resin, then through
a cellulose ester membrane having openings not exceeding 0.45 µm.3 Do not use
copper tubing. Flush the discharge lines before water is dispensed into test
vessels. When the low conductivity specification can no longer be met, replace
the deionizer cartridge.
Methyl Red Solution— Dissolve 24 mg of methyl red sodium in Purified Water to
make 100 mL. If necessary, neutralize the solution with 0.02 N sodium hydroxide
or acidify it with 0.02 N sulfuric acid so that the titration of 100 mL of
High-Purity Water, containing 5 drops of indicator, does not require more than
0.020 mL of 0.020 N sodium hydroxide to effect the color change of the
indicator, which should occur at a pH of 5.6.
Powdered Glass Test
Rinse thoroughly with Purified Water 6 or more containers selected at random,
and dry them with a current of clean, dry air. Crush the containers into
fragments about 25 mm in size, divide about 100 g of the coarsely crushed glass
into three approximately equal portions, and place one of the portions in the
special mortar. With the pestle in place, crush the glass further by striking 3
or 4 blows with the hammer. Nest the sieves, and empty the mortar into the No.
20 sieve. Repeat the operation on each of the two remaining portions of glass,
emptying the mortar each time into the No. 20 sieve. Shake the sieves for a
short time, then remove the glass from the Nos. 20 and 40 sieves, and again
crush and sieve as before. Repeat again this crushing and sieving operation.
Empty the receiving pan, reassemble the nest of sieves, and shake by mechanical
means for 5 minutes or by hand for an equivalent length of time. Transfer the
portion retained on the No. 50 sieve, which should weigh in excess of 10 g, to a
closed container, and store in a desiccator until used for the test.
Spread the specimen on a piece of glazed paper, and pass a magnet through it to
remove particles of iron that may be introduced during the crushing. Transfer
the specimen to a 250-mL conical flask of resistant glass, and wash it with six
30-mL portions of acetone, swirling each time for about 30 seconds and carefully
decanting the acetone. After washing, the specimen should be free from
agglomerations of glass powder, and the surface of the grains should be
practically free from adhering fine particles. Dry the flask and contents for 20
minutes at 140, transfer the grains to a weighing bottle, and cool in a
desiccator. Use the test specimen within 48 hours after drying.
Procedure— Transfer 10.00 g of the prepared specimen, accurately weighed, to a
250-mL conical flask that has been digested (aged) previously with High-Purity
Water in a bath at 90 for at least 24 hours or at 121 for 1 hour. Add 50.0 mL of
High-Purity Water to this flask and to one similarly prepared to provide a
blank. Cap all flasks with borosilicate glass beakers that previously have been
treated as described for the flasks and that are of such size that the bottoms
of the beakers fit snugly down on the top rims of the containers. Place the
containers in the autoclave, and close it securely, leaving the vent cock open.
Heat until steam issues vigorously from the vent cock, and continue heating for
10 minutes. Close the vent cock, and adjust the temperature to 121, taking 19 to
23 minutes to reach the desired temperature. Hold the temperature at 121 ± 2.0
for 30 minutes, counting from the time this temperature is reached. Reduce the
heat so that the autoclave cools and comes to atmospheric pressure in 38 to 46
minutes, being vented as necessary to prevent the formation of a vacuum. Cool
the flask at once in running water, decant the water from the flask into a
suitably cleansed vessel, and wash the residual powdered glass with four 15-mL
portions of High-Purity Water, adding the decanted washings to the main portion.
Add 5 drops of Methyl Red Solution, and titrate immediately with 0.020 N
sulfuric acid. If the volume of titrating solution is expected to be less than
10 mL, use a microburet. Record the volume of 0.020 N sulfuric acid used to
neutralize the extract from 10 g of the prepared specimen of glass, corrected
for a blank. The volume does not exceed that indicated in Table 2 for the type
of glass concerned.
Water Attack at 121
Rinse thoroughly 3 or more containers, selected at random, twice with
High-Purity Water.
Procedure— Fill each container to 90% of its overflow capacity with High-Purity
Water, and proceed as directed for Procedure under Powdered Glass Test,
beginning with “Cap all flasks,” except that the time of autoclaving shall be 60
minutes instead of 30 minutes, and ending with “to prevent the formation of a
vacuum.” Empty the contents from 1 or more containers into a 100-mL graduated
cylinder, combining, in the case of smaller containers, the contents of several
containers to obtain a volume of 100 mL. Place the pooled specimen in a 250-mL
conical flask of resistant glass, add 5 drops of Methyl Red Solution, and
titrate, while warm, with 0.020 N sulfuric acid. Complete the titration within
60 minutes after opening the autoclave. Record the volume of 0.020 N sulfuric
acid used, corrected for a blank obtained by titrating 100 mL of High-Purity
Water at the same temperature and with the same amount of indicator. The volume
does not exceed that indicated in Table 2 for the type of glass concerned.
Arsenic
Arsenic 211— Use as the Test Preparation 35 mL of the water from one Type I
glass container or, in the case of smaller containers, 35 mL of the combined
contents of several Type I glass containers, prepared as directed for Procedure
under Water Attack at 121: the limit is 0.1 µg per g.
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