An elastomeric closure may be of synthetic or natural origin. It is generally a complex mixture of many ingredients. These include the basic polymer, fillers, accelerators, vulcanizing agents, and pigments. The properties of the elastomeric closure are dependent not only upon these ingredients, but also on the processing procedure, such as mixing, milling, dusting agents used, molding, and curing.
Factors such as cleansing procedures, contacting media, and conditions of storage may also affect the suitability of an elastomeric closure for a specific use. Evaluation of such factors should be made by appropriate additional specific tests to determine the suitability of an elastomeric closure for its intended use. Criteria for the selection of an elastomeric closure should also include a careful review of all the ingredients to assure that no known or suspected carcinogens, or other toxic substances are added.
Physicochemical Test Procedures
The following tests are designed to determine pertinent physicochemical extraction characteristics of elastomeric closures. Since the tests are based on the extraction of the elastomer, it is essential that the designated amount of surface area of sample be available. In each case, the specified surface area is available for extraction at the designated temperature. The test methods are devised to detect the majority of expected variations.
Extraction Solvents—
A:
Purified Water.
B:
Drug product vehicle (where applicable).
C:
Isopropyl alcohol.
Apparatus—
Autoclave—
Use an autoclave capable of maintaining a temperature of 121 ± 2
, equipped with a thermometer, a pressure gauge, and a rack adequate to accommodate the test containers above the water level.
Oven—
Use an oven, preferably a forced-draft model, that will maintain an operating temperature of 105
± 2
.
Reflux Apparatus—
Use a suitable reflux apparatus having a capacity of about 500 mL.
Procedure—
Preparation of Sample—
Place in a suitable extraction container a sufficient number of elastomeric closures to provide 100 cm
2 of exposed surface area. Add 300 mL of purified water to each container, cover with a suitable inverted beaker, and autoclave at 121 ± 0.5
for 30 minutes.
[NOTE—Adjust so that the temperature rises rapidly, preferably within 2 to 5 minutes.
] Decant, using a stainless steel screen to hold the closures in the containers. Rinse with 100 mL of purified water, gently swirl, and discard the rinsings. Repeat with a second 100-mL portion of purified water. Treat all
blank containers in a similar manner.
Extracts (with use of Extraction Solvent A)—
Place a properly prepared
sample, having an exposed surface area of 100 cm
2, in a suitable container, and add 200 mL of purified water. Cover with a suitable inverted beaker, and extract by heating in an autoclave at 121
for 2 hours, allowing adequate time for the liquid within the container to reach the extraction temperature. Allow the autoclave to cool rapidly, and cool to room temperature. Treat the
blank container in a similar manner.
Extracts (with use of Extraction Solvent B or C)—
Place a properly prepared sample, having an exposed surface area of 100 cm2, in a suitable Reflux Apparatus containing 200 mL of Extraction Solvent, and reflux for 30 minutes. Treat the blank in a similar manner.
Turbidity—
[NOTE—Use
Extracts prepared with
Extraction Solvent A,
B, or
C.
] Agitate the container, and transfer a sufficient quantity of
Extract, diluted with
Extraction Solvent, if necessary, to a cell. Measure the turbidity in a suitable ratio turbidimeter (see
Spectrophotometry and Light-Scattering 
851
) against fixed reproducible standards.
* The turbidity is the difference between the values obtained for the blank and the sample expressed in Nephelometric Turbidity Units (NTU), an arbitrary linear numerical scale expressing a haze range from absolute clarity to the zone of turbidity.
Reducing Agents—
[NOTE—Use Extracts prepared with Extraction Solvent A.] Agitate the container, transfer 50 mL of sample extract to a suitable container, and titrate with 0.01 N iodine VS, using 3 mL of starch TS as the indicator. Treat the blank extract in a similar manner. The difference between the blank and the sample titration is expressed in mL of 0.01 N iodine.
Heavy Metals 231—
[NOTE—Use
Extracts prepared with
Extraction Solvent A or
B.
] Transfer 20 mL of the
blank and the
sample extracts to separate color-comparison tubes. Transfer 2, 6, and 10 mL of
Standard Lead Solution into separate color-comparison tubes, add 2 mL of 1 N acetic acid to each tube, and adjust the volume to 25 mL with purified water. Add 10 mL of freshly prepared
hydrogen sulfide TS to each tube, mix, allow to stand for 5 minutes, and view downward over a white surface. Determine the amount of heavy metals in the
blank and in the
sample. The heavy metals content is the difference between the
blank and the
sample.
pH Change—
[NOTE—Use Extracts prepared with Extraction Solvent A or B, adding to extracts obtained with Solvent A sufficient potassium chloride to provide a concentration of 0.1%.] Determine the pH of sample extracts A and B potentiometrically, performing blank determinations with blank extracts A and B, and making any necessary corrections. The pH change is the difference between the blank and the sample.
Total Extractables—
[NOTE—Use
Extracts prepared with
Extraction Solvent A,
B, or
C.
] Agitate the containers, and transfer 100-mL aliquots of the
blank and the
sample to separate, tared evaporating dishes. Evaporate on a steam bath to dryness (
Extracts prepared with
Extraction Solvent C) or in an oven at 100
, dry at 105
for 1 hour, cool in a desiccator, and weigh. Calculate the total extractables, in mg, by the formula:
2(
WU 
WB),
in which
WU is the weight, in mg, of residue found in the sample extract aliquot; and
WB is the weight, in mg, of residue found in the blank solution aliquot.
