BP506-P INDUSTRIAL PHARMACY I

AHNIK SANJIB KASHYAP

EXPERIMENT-10

Aim:
Evaluation of glass ampules as per IP

Reference:
European pharmacopoeia 7.0, page- 363-367 Indian Pharmacopoeia 2207, Volume 1, page no. 363-
365

Theory:
Glass articles are intended to come into direct contact with pharmaceutical preparations.
Colourless glass is highly transparent in visible spectrum. Coloured glass is obtained by addition of
small amount of metal oxides, chosen according to the desired spectral absorbance.
Neutral glass is a borosilicate glass containing significance amount of boric acid, aluminium oxide
alkali or alkaline earth oxides.
Due to its composition, neutral glass has a high hydrolytic resistance and a high thermal shock
resistance.
Hydrolytic stability for glass ampules for pharmaceutical use is expressed by the resistance to release
of soluble mineral substances into water under prescribed conditions of contact between inner
surface of container/ glass grains and water. Hydrolytic resistance is evaluated by titrating released
alkali. As per hydrolytic resistance, glass containers are classified as follows:
Type 1 glass ampules: Neutral glass, with a high hydrolytic resistance to the composition of glass
itself.
Type 2 glass ampules: Usually made of soda lime silica glass with a high hydrolytic resistance
resulting from suitable treatment of surface.
Type 3 glass ampules: Usually of soda lime silica glass with only moderate hydrolytic resistance.
APPLICATION OF DIFFERENT TYPE OF GLASS AMPULES-

• Type 1 glass ampule: Suitable for most preparation whether or not for parenteral
preparation.

• Type 2 glass ampule: Suitable for most acidic and neutral, aqueous preparation whether or
not parenteral administration.

• Type 3 glass ampule: Suitable for non-aqueous preparation for parenteral preparation, for
powders for parenteral administration and for preparation not for parenteral administration.

To define the quality of glass ampules according to intended use, one or more of the following tests
are necessary-

Type of container Tests to be performed

Type I and II glass ampules Test A (surface test)

Type I glass container (to distinguish from Test B (glass grain test) or test C (etching
type II and type III glass containers) test)
Test I & II glass containers to determine
Test A and B
whether the hydrolytic resistance is due to
OR
chemical composition or due to surface
Test A and C
treatment

Test A: hydrolytic resistance of the inner surfaces of glass containers (surface test)
(Determination is done on unused containers)

Procedure:
1. Cleaning: Shortly before test, remove any debris or dust and rinse each am- pule with water.
Heat closed ampule on water bath or in an air oven at about 50 ℃ for 2 minutes.

2. Filling and heating: Fill the ampules with freshly prepared distilled water to the maximum
volume compatible with sealing them by fusion of glass and seal them.
 3. Fill the bottles or vials to 90% of their calculated overflow volume and cover them with
borosilicate glass dishes/ aluminium foil previously rinsed with freshly prepared distilled
water.

4. Place the container in an autoclave containing water and heat the container at 121 ℃ for 60
minutes and reduce the temperature to 100 ℃ over 40 minutes.

5. Remove the containers from autoclave and cool them in tap water.

6. Carry out the titration within one hour.

7. Combine the liquids from container and measure the volume of test solution in conical flask
and add 0.15 mL of methyl red solution for each 50 mL liquid.

8. Titrate with 0.01M hydrochloric acid taking as the end point the colour obtained by repeating
the operation using same volume of freshly prepared dis- tilled water.

9. Calculate the volume of 0.01M hydrochloric acid required for each 100mL of test solution.

Capacity of container (corresponding to 90%

Type I/II glass (mL) Type III glass (mL)

Not more than 1 2 20

More than 1 but not less than 2 1.8 17.6

More than 2 but not less than 5 1.3 13.2

More than 5 but not less than 10 1 10.2

More than 10 but not less than 20 0.8 8.1

More than 20 but not less than 50 0.6 6.1

More than 50 but not less than 100 0.5 4.8

More than 100 but not less than 200 0.4 3.8

More than 200 but not less than 500 0.3 2.9

More than 500 0.2 2.2

Procedure:

1. Rinse the containers to be tested with water and dry in oven.

2. Wrap 3 glass articles in clean paper and crush to produce 2 samples of about 100 gm each.

3. place 30 - 40gm of pieces from 1 of the samples in mortar and strike it heavily once only with
hammer.

4. Transfer the contents of mortar, to the coarset sieve number 710

5. Shake the set of sieves a short time by hand and removed the unpassed glass. Set of sieves –
a. sieve no. 710
b. sieve no. 425
c. sieve no. 300

6. Submit the removed portion to further fracture, repeating the operation until about log of
glass remains on sieve a.

7. Reject this portion and the portion which passes through sieve c.

8. Reasonable the set of sieve and shake for 5 minutes.

9. Transfer to a weighing bottle those glass grains which passes through sieve b and retain in
sieve c.

10. Repeat the crushing and sieving process with another glass sample and thus, 2 samples of
grains, each of which shall be in excess of 10 gm, are obtained.

11. Spread each sample on a piece of clean glazed paper and remove any iron particle by passing
magnet over them.

12. Transfer each sample into a beaker for cleaning. Add to the grains in each beaker 30 mL of
acetone and scour the grain and allow to settle and decant as much acetone as possible.

13. Fill the both of ultrasonic vessel with water at room temperature and immerse it with acetone
up to water level.

14. Apply ultrasound for 1 minute.

15. Remove excess of acetone and dry the grains.

17. Weigh 10.00 g in 2 separate conical flask and add 50 mL of water in each. Pipette 50 mL water
in 3rd flask as blank.

18. Cover the flask and place them in autoclave at ambient temperatures. Maintain the
temperature at 121℃ for 30±1 minute.

19. Remove the flask and cool them in running tap water.

20. Add 0.05 mL of methyl red solution to each and titrate the blank solution with 0.02M
hydrochloric acid.

21. Titrate the test solution until the colour matches with that obtained with blank.

22. Subtract the titration volume for blank solution from that for the test solution.

23. Calculate the main value in millilitres of 0.02M HCl per g of sample.

LIMITS:
• Type I glass containers require not more than 0.1mL of 0.02M HCl per gram of glass.

• Type II and Type III glass containers require not more than 0.85mL of 0.02M HCl per gram of
glass.

Test C: To determine whether the containers have been surface-treated

Procedure:

1. Rinse the container with water and fill to the brim-full point with a mixture of 1 volume
hydrofluoric acid and 9 volume of hydrochloric acid and allow to stand for 10 minutes.

2. Empty the containers and rinse carefully 5 times with water.

3. Immediately before test, rinse once again with water.

5. If the results are considerably higher than those obtained from original surfaces (by about a
factor of 5-10), the samples are surface treated.

6. If the ampules are not treatment, the new values are slightly lower than those obtained in
previous tests.

Distinction between type I and type II glass containers-

Type 1 Type II

Values are closely similar to those found in the Values greatly exceed those found in the test
test for surface hydrolytic resistance for type I for surface hydrolytic resistance and similar
glass containers but not larger than those for type III glass
container.

Conclusion:
Hence, the glass containers were evaluated for various parameters with the help of SURFACE
TEST, GLASS GRAIN TEST and ETCHING TEST. It was found that the glass container for
pharmaceutical use have capacity hydrolytic resistance which differs them from one another. This
makes their application ’vary’ for storage of different pharmaceutical preparations.

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