POLYPROPYLENE CONTAINERS
The standards and tests provided in this section characterize polypropylene containers, produced from either homopolymers or copolymers, that are interchangeably suitable for packaging dry solid and liquid oral dosage forms.
Where suitable stability studies have been performed to establish the expiration date of a particular dosage form in the appropriate polypropylene container, then any other polypropylene container meeting these requirements may be similarly used to package such dosage form, provided that the appropriate stability programs are expanded to include the alternative container, in order to assure that the potency, identity, strength, quality, and purity of the dosage form are maintained throughout the expiration period.
Propylene polymers are long-chain polymers synthesized from propylene or propylene and other olefins under controlled conditions of heat and pressure, with the aid of catalysts. Examples of other olefins most commonly used include ethylene and butene. The propylene polymers, the ingredients used to manufacture the propylene polymers, and the ingredients used in the fabrication of the containers conform to the applicable sections of the Code of Federal Regulations, Title 21.
Factors such as plastics composition, processing and cleaning procedures, contacting media, inks, adhesives, absorption, adsorption and permeability of preservatives, and conditions of storage may also affect the suitability of a plastic for a specific use. The suitability of a specific polypropylene must be established by appropriate testing.
Polypropylene has a distinctive IR spectrum and possesses characteristic thermal properties. It has a density between 0.880 and 0.913 g per cm3. The permeation properties of molded polypropylene containers may be altered when reground polymer is incorporated, depending on the proportion of reground material in the final product. Other properties that may affect the suitability of polypropylene used in containers for packaging drugs are the following: oxygen and moisture permeability, modulus of elasticity, melt flow index, environmental stress crack resistance, and degree of crystallinity after molding. The requirements in this section are to be met when dry solid and liquid oral dosage forms are to be packaged in a container defined by this section.
Multiple Internal Reflectance
APPARATUS
Use an IR spectrophotometer capable of correcting for the blank spectrum and equipped with a multiple internal reflectance accessory and a KRS-5 internal reflection plate. A KRS-5 crystal 2-mm thick having an angle of incidence of 45
provides a sufficient number of reflections.
PREPARATION OF SPECIMEN
Cut 2 flat sections, representative of the average wall thickness of the container, and trim them as necessary to obtain segments that are convenient for mounting in the internal reflectance accessory. Taking care to avoid scratching the surfaces, wipe the specimens with dry paper, or if necessary with a soft cloth dampened with methanol, and permit them to dry. Securely mount the specimens on both sides of the KRS-5 internal reflection plate, ensuring adequate surface contact. Prior to mounting the specimens on the plate, they may be compressed to flat uniform films by exposure to temperatures between 220
and 240
. The specimen's time/temperature history during this operation should be limited to that necessary to mold the films.
PROCEDURE
Place the mounted specimen sections within the multiple internal reflectance accessory, and place the assembly in the specimen beam of the IR spectrophotometer. Adjust the specimen position and mirrors within the accessory to permit maximum light transmission of the unattenuated reference beam. (For a double beam instrument, upon completing the adjustment in the accessory, attenuate the reference beam to permit full-scale deflection during the scanning of the specimen.) Determine the IR spectrum from 3500 to 600 cm-1. The corrected spectrum of the specimen exhibits major absorption bands only at the same wavelengths as the spectrum of the USP Reference Standard for either a polypropylene homopolymer or copolymer, similarly determined.
Thermal Analysis
Cut a section weighing about 12 mg, and place it in the test specimen pan. Intimate contact between the pan and the thermocouple is essential for reproducible results. Determine the thermogram under nitrogen at temperatures ranging from ambient to 30
above the melting point. Maintain the temperature for 10 minutes, then cool to 50
below the peak crystallization temperature at a rate of 10
to 20
per minute, using equipment capable of performing the determinations as described under
Thermal Analysis 891. The thermogram of the specimen is similar to the thermogram of the appropriate USP Reference Standard for polypropylene. The temperatures of the endotherms and exotherms in the thermogram do not differ from those of the USP Reference Standard for homopolymers by more than 12.0
or from those of the USP Reference Standard for copolymers by more than 6.0
.
Light Transmission
Polypropylene containers intended to provide protection from light meet the requirements under Light Transmission.
Water Vapor Permeation
Fit the containers with impervious seals obtained by heat-sealing the bottles with an aluminum foil-polyethylene laminate or other suitable seal. Test the containers as described under
ContainersPermeation 671. The containers meet the requirements if the moisture permeability exceeds 15 mg per day per L in not more than one of the 10 test containers and exceeds 25 mg per day per L in none of them.
Heavy Metals and Nonvolatile Residue
Prepare extracts of specimens for these tests as directed for
Procedure under
Physicochemical TestsPlastics, except that for each 20 mL of
Extracting Medium the portion shall be 60 cm
2, regardless of thickness.
HEAVY METALS
Containers meet the requirements for
Heavy Metals under
Physicochemical TestsPlastics.
NONVOLATILE RESIDUE
Proceed as directed for
Nonvolatile Residue under
Physicochemical TestsPlastics, except that the blank shall be the same solvent used in each of the tests set forth below. The difference between the amounts obtained from the specimen and the blank does not exceed 10.0 mg when water maintained at a temperature of 70
is used as the extracting medium, does not exceed 60.0 mg when alcohol maintained at a temperature of 70
is used as the extracting medium, and does not exceed 225.0 mg when hexanes maintained at a temperature of 50
is used as the extracting medium. Containers meet these requirements for
Nonvolatile Residue for all of the above extracting media.
[NOTEHexanes and alcohol are flammable. When evaporating these solvents, use a current of air with the water bath; when drying the residue, use an explosion-proof oven.
]
Buffering Capacity
Prepare extracts of the specimen as described for Procedure under Physicochemical TestsPlastics. Containers meet the requirements for Buffering Capacity under Physicochemical TestsPlastics.