The majority of chemical testing is required on primary component. The type of testing required depends on the type of component used.
- Glass vials and ampules – the USP XXII requirements for glass containers are chemical and light resistant.
- Plastic primary components – the testing is more extensive with plastic components, requiring both biological and physicochemical test.
Water Attack Test
This test is used only with containers that have been exposed to sulphur dioxide fumes under controlled humidity conditions. Such treatment neutralizes the surface alkali. The glass becomes chemically more resistant. The principle involved in the water attack test is to determine whether the alkali leached from the surface of a container is within the specified limits or not. Since the inner surface is under test the entire container has to be used. The amount of acid that is necessary to neutralize the released alkali from the surface is estimated, the leaching of alkali is accelerated using elevated temperature for a specified time. Methyl red indicator is used to determine the end point.
Powdered Glass Test
It is done to estimate the amount of alkali leached from the powdered glass which usually happens at the elevated temperatures. When the glass is powdered, leaching of alkali is enhanced, which can be titrated with 0.02 N sulphuric acid using methyl red as indicator.
- Step 1: Preparation of glass specimen – Few containers are rinsed thoroughly with purified water and dried with stream of clean air. Grind the containers in a mortar to a fine powder and pass through sieve no.20 and 50.
- Step 2: Washing the specimen: 10 grams of the above specimen is taken into 250 mL conical flask and was it with 30 mL acetone. Repeat the washing, decant and dried after which it is used within 48 hour.
10 grams of sample is added with 50 mL of high purity water in a 250 mL flask. Place it in an autoclave at 121°C +/- 2°C for 30 minutes. Cool it under running water. Decant the solution into anther flask, wash again with 15 mL high purity water and again decant. Titrate immediately with 0.02 N sulphuric acid using methyl red as indicator and record the volume.
Hydrolytic Resistance of Glass Containers
- Rinse each container at least three times with C02 free water and fill with the same to their filling volume. Also fill and cover the vials and bottles and keep in autoclave. Heat to 100°C for 10 minutes and allow the steam to issue from the vent cork. Rise the temperature from 100°C to 121°C over 20 minutes. Maintain the temperature at 121°C to 100°C over 40 minutes venting to prevent vacuum.
- Remove the container from autoclave, cool and combine the liquids being examined. Measure the volume of test solution into a conical flask and titrate with 0.01 M HCl using methyl red as an indicator. Perform blank with water and the difference between the titration represents the volume of HCl consumed by the test solution.
- This test is for glass containers intended for aqueous parenteral. Wash the inner and outer surface of container with fresh distilled water for 5 minutes. Preparation test as described in the test for hydrolytic resistance for an adequate number of samples to produce 50 mL pipette out of the 10 mL solution all the combined contents of all the containers to the flask.
- Add 10 mL of nitric acid to dryness on the water bath, dry the residue in oven at 130°C for 30 minutes. Cool and add 10 mL hydrogen molybdate reagent. Swirl to dissolve and heat under water bath and reflux for 25 minutes. Cool to room temperature and determine the absorbance at 840 nm.
- Do the blank with 10 mL hydrogen molybdate. The absorbance of the test solution should not exceed the absorbance obtained by repeating the determination using 0.1 mL of arsenic standard solution.
Thermal Shock Test
- Place the samples in upright position in a tray. Immerse the tray into a hot water for a given time and transfers to cold water bath, temperature of both are closely controlled. Examine cracks or breaks before and after the test. The amount of thermal shock a bottle can withstand depends on its size, design and glass distribution. Small bottles withstand a temperature differential of 60 to 80°C and 1 pint bottle 30 to 40° C. A typical test uses 45°C temperature difference between hot and cold water.
Internal Bursting Pressure Test
The most common instrument used is American glass research increment pressure tester.
- The test bottle is filled with water and placed inside the test chamber.
- A scaling head is applied and the internal pressure automatically raised by a series of increments each of which is held for a set of time.
- The bottle can be checked for predetermined pressure level and the test continues until the container finally bursts.
Drug filled container is placed in a container filled with colored solution (due to addition of dye) which is at high pressure compared to the pressure inside the glass container so that the colored solution enters the container if any cracks or any breakage is present.