GLASS: PACKAGING MATERIAL USED IN PHARMA
American Society for Testing and Materials (ASTM) defines glass as an inorganic product of fusion that has cooled to a rigid condition without crystallizing. ASTM further states that glass is typically hard and brittle and has a conchoidal fracture. Glass may be colorless or colored. It is transparent but may be made opaque or translucent. Glass is non-crystalline, is amorphous in structure, and may be formed from both organic and inorganic materials.
The USP and EP have provided similar classifications that are summarized below:-
TYPE I GLASS:- Type I glass containers comprise a borosilicate glass with about 80% SiO2 and 10% B2O3 and smaller amounts of Al2O3 and Na2O. It is inert and has the lowest coefficient of thermal expansion. It is least likely to crack when a sudden temperature differential occurs. It is commonly used to make ampules and vials for parenteral use. It is used for solutions that can dissolve basic oxides to cause an increase in pH that could alter the efficacy or potency of the drug.
- USP describes Type I glass as:- highly resistant borosilicate glass, and usually used for packaging acidic and neutral parenteral preparations. Also, where stability data demonstrates their suitability, Type I are used for alkaline parenteral preparations.
- EP describes Type I glass as:- neutral glass with high hydrolytic resistance owing to the chemical composition of the glass itself. Type I is suitable for all preparations whether or not for parenteral use and for human blood and blood components.
TYPE II GLASS:- A dealkalized form of soda-lime glass with higher levels of Na2O and CaO. It is less resistant to leaching than Type I but more than Type III. However, to make Type II and other types more resistant to leaching, the surface can be treated with SO2 to convert surface oxides present to soluble salts that are then washed off.
This surface treatment is effective for containers used once and those repeatedly exposed to heat. Type II has a lower melting point than Type I and, therefore, is easier to fabricate. It has a higher coefficient of thermal expansion, and is used in solutions that can be buffered to maintain a pH below 7.
- USP:- Soda-lime glass that is suitably dealkalized and is used for packaging acidic and neutral parenteral preparations, and, also where stability data demonstrates their suitability, is used for alkaline parenteral preparations.
- EP:- Soda-lime silica glass with high hydrolytic resistance resulting from suitable treatment of the surface. These containers are suitable for acidic and neutral aqueous preparations for parenteral use.
TYPE III GLASS:- A soda-lime glass containing same amount of sodium and oxide levels as in Type II but contains more leachable oxides of other elements. And because of its high reactivity, it is used to package anhydrous liquids and other dry products.
- USP:- These are soda-lime glass containers that are usually not used for parenteral preparations, except where suitable sensitivity test data indicates that Type III is satisfactory for the parenteral preparations that are packaged therein.
- EP:- These are soda-lime glasses with only moderate hydrolytic resistance. They are suitable for non-aqueous preparations for parenteral use, for powders for parenteral use, and for preparations not for parenteral use.
TESTS:- These glass containers for pharmaceutical use have to comply with relevant tests such as tests for hydrolytic resistance for EP and tests chemical resistance for USP. The test procedure and methods are slightly different for each of the pharmacopeias. For the four types of glasses, there are designated relevant test types and expected limits.
USP has provided procedure and test requirements for three types of tests. These are the:-
- Powdered glass test,
- The water attack test, and
- The arsenic test.
Apparatus used for these tests:-
- Autoclave:- An autoclave capable of maintaining a temperature of 121±20C, 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 is used.
- Mortar and Pestle:- A hardened-steel mortar and pestle, made according to the specifications in the accompanying illustration.
- Other Equipment:-
- Sieves, about 20.3cm (8 in.), made of stainless steel including the Nos. 20, 40, and 50 sieves, along with the pan and cover (Openings of Standard Sieves 811).
- 250ml 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 are used.
Reagents used for these tests:-
- High-Purity Water:- The water used in these tests has conductivity at 25OC, 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 µ 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 five drops of indicator, does not require more than 0.020 ml of 0.020 N-sodium hydroxide to affect the color change of the indicator, which should occur at a pH of 5.6.
POWDERED GLASS TESTS FOR TYPES I AND II:-
- Rinse thoroughly with purified water six or more containers selected at random, and dry them with a current of clean, dry air.
- Crush the containers into fragments about 25mm 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 three or four 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, and 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 five 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 sec 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 min at 1400C, transfer the grains to a weighing bottle, and cool in a desiccator. Use the test specimen within 48 hr. after drying.
- Transfer 10.0 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 900C for at least 24 hr or at 1210C for 1 hr.
- 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 min.
- Close the vent cock, and adjust the temperature to 1210C, taking 19–23 min to reach the desired temperature.
- Hold the temperature at 121±20C for 30 min, counting from the time this temperature is reached.
- Reduce the heat so that the autoclave cools and comes to atmospheric pressure in 38–46 min, 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 five 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 given standard document.
LIGHT TRANSMISSION TEST:- In addition to the above-mentioned tests, compendial limits are provided for light transmission for colored light protecting glass containers. These containers intended to provide protection from light or supplied as ‘‘light resistant’’ are expected to meet the requirements for ‘‘light transmission’’ in this section. In this test, a spectrophotometer of suitable sensitivity is used to cut a section of the glass container. The transmittance of the section is measured, and the observed light transmission is not expected to exceed the limits provided in Table below.
- There are differences in testing glass as a container compared to glass as a material (glass-grain tests). The glass surface area-to-solution volume ratio is higher in grain tests, resulting in higher concentrations of glass constituents in solution after autoclaving. This facilitates solution analysis and differentiation between glasses.
- The other major difference is the presence of forming deposits, in the case of containers made from tubing, which influences test results. Blow-molded container test results are not affected by deposits.
- WATER ATTACK AT 1210C FOR TYPE II GLASSES:- Rinse thoroughly twice three or more containers, selected at random, 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 min instead of 30 min, and ending with ‘‘to prevent the formation of a vacuum.’’
- Empty the contents from one 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 five drops of methyl red solution, and titrate, while warm, with 0.020 N-sulfuric acid.
- Complete the titration within 60 min 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 1 for the type of glass concerned.
- Remove any debris or dust from six or more containers. Shortly before the test, rinse each container carefully at least twice with purified water and allow standing. Immediately before testing, empty the containers rinse once and allow them to drain.
- The containers are then filled with purified water up to the filling volume, for vials and bottles 90% of capacity and for ampoules up to the shoulder.
- Place the containers on the tray in the autoclave and heat the autoclave to 1000C while allowing the steam to issue from the vent cock for 10 min.
- The temperature is then raised from 1000C to 1210C at a rate of 10C per min, once at 1210C the temperature is then maintained for 60 min. After the 60 min timeframe, the temperature is lowered from 1210C to 1000C at a rate of 0.50C per min. Once the autoclave has cooled down to 950C, the containers are removed and placed in a water bath at 800
- For the test, the contents of the autoclaved containers are combined into a conical flask. The same volume of purified water is placed into a second similar flask as a blank. Add to each flask 0.05 ml of methyl red solution for each 25 ml of liquid.
- Then titrate the blank with 0.01M hydrochloric acid and the test liquid until the color of the testing solution is the same as that obtained for the blank. Subtract the value found for the blank titration from that found for the test liquid, and express the results in milliliters of 0.01M hydrochloric acid per 100 ml.
- The results, or the average of the results if more than one titration is performed, are not greater than the values stated in Table below.
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