U.S. PHARMACOPEIA

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661 CONTAINERS
Many Pharmacopeial articles are of such nature as to require the greatest attention to the containers in which they are stored or maintained even for short periods of time. While the needs vary widely and some of them are not fully met by the containers available, objective standards are essential. It is the purpose of this chapter to provide such standards as have been developed for the materials of which pharmaceutical containers principally are made, i.e., glass and plastic.
A container intended to provide protection from light or offered as a “light-resistant” container meets the requirements for Light Transmission, where such protection or resistance is by virtue of the specific properties of the material of which the container is composed, including any coating applied thereto. A clear and colorless or a translucent container that is made light-resistant by means of an opaque enclosure (see General Notices) is exempt from the requirements for Light Transmission.
Containers composed of glass meet the requirements for Chemical Resistance—Glass Containers, and containers composed of plastic and intended for packaging products prepared for parenteral use meet the requirements under Biological Tests—Plastics and Physicochemical Tests—Plastics.
Where dry oral dosage forms, not meant for constitution into solution, are intended to be packaged in a container defined in the section Polyethylene Containers, the requirements given in that section are to be met.
Guidelines and requirements under Repacking into Single-Unit Containers and Unit-Dose Containers for Nonsterile Solid and Liquid Dosage Forms apply to official dosage forms that are repackaged into single-unit or unit-dose containers or mnemonic packs for dispensing pursuant to prescription.

LIGHT TRANSMISSION
Apparatus1 Use a spectrophotometer of suitable sensitivity and accuracy, adapted for measuring the amount of light transmitted by either transparent or translucent glass or plastic materials used for pharmaceutical containers. For transparent glass or plastic pharmaceutical containers, use a spectrophotometer of suitable sensitivity and accuracy for measuring and recording the amount of light transmitted. For translucent glass or plastic pharmaceutical containers, use a spectrophotometer as described above that, in addition, is capable of measuring and recording light transmitted in diffused as well as parallel rays.
Preparation of Specimen—
Glass— Break the container or cut it with a circular saw fitted with a wet abrasive wheel, such as a carborundum or a bonded diamond wheel. Select sections to represent the average wall thickness in the case of blown glass containers, and trim them as necessary to give segments of a size convenient for mounting in the spectrophotometer. After cutting, wash and dry each specimen, taking care to avoid scratching the surfaces. If the specimen is too small to cover the opening in the specimen holder, mask the uncovered portion of the opening with opaque paper or masking tape, provided that the length of the specimen is greater than that of the slit in the spectrophotometer. Immediately before mounting in the specimen holder, wipe the specimen with lens tissue. Mount the specimen with the aid of a tacky wax, or by other convenient means, taking care to avoid leaving fingerprints or other marks on the surfaces through which light must pass.
Plastic— Cut circular sections from two or more areas of the container, and wash and dry them, taking care to avoid scratching the surfaces. Mount in the apparatus as described for Glass.
Procedure— Place the section in the spectrophotometer with its cylindrical axis parallel to the plane of the slit and approximately centered with respect to the slit. When properly placed, the light beam is normal to the surface of the section and reflection losses are at a minimum.
Measure the transmittance of the section with reference to air in the spectral region of interest, continuously with a recording instrument or at intervals of about 20 nm with a manual instrument, in the region of 290 to 450 nm.
Limits— The observed light transmission does not exceed the limits given in Table 1 for containers intended for parenteral use.
Table 1.Limits for Glass Types I, II, and III and Plastic Classes I–VI
Maximum Percentage of Light Transmission at Any Wavelength Between 290 and 450 nm
Nominal Size
(in mL)
Flame-sealed
Containers
Closure-sealed
Containers
1 50 25
2 45 20
5 40 15
10 35 13
20 30 12
50 15 10
NOTE—Any container of a size intermediate to those listed above exhibits a transmission not greater than that of the next larger size container listed in the table. For containers larger than 50 mL, the limits for 50 mL apply.
The observed light transmission for containers of Type NP glass and for plastic containers for products intended for oral or topical administration does not exceed 10% at any wavelength in the range from 290 to 450 nm.

CHEMICAL RESISTANCE—GLASS CONTAINERS
The following tests are designed to determine the resistance to water attack of new (not previously used) glass containers. The degree of attack is determined by the amount of alkali released from the glass under the influence of the attacking medium under the conditions specified. This quantity of alkali is extremely small in the case of the more resistant glasses, thus calling for particular attention to all details of the tests and the use of apparatus of high quality and precision. The tests should be conducted in an area relatively free from fumes and excessive dust.
Glass Types— Glass containers suitable for packaging Pharmacopeial preparations may be classified as in Table 2 on the basis of the tests set forth in this section. Containers of Type I borosilicate glass are generally used for preparations that are intended for parenteral administration. Containers of Type I glass, or of Type II glass (i.e., soda-lime glass that is suitably dealkalized) are usually used for packaging acidic and neutral parenteral preparations. Type I glass containers, or Type II glass containers (where stability data demonstrate their suitability), are used for alkaline parenteral preparations. Type III soda-lime glass containers usually are not used for parenteral preparations, except where suitable stability test data indicate that Type III glass is satisfactory for the parenteral preparations that are packaged therein. Containers of Type NP glass are intended for packaging nonparenteral articles, i.e., those intended for oral or topical use.
Table 2.Glass Types and Test Limits
Type General
Description1
Type of Test Limits
Size,2
mL
mL of 0.020
N Acid
I Highly resistant,
borosilicate
glass
Powdered Glass All 1.0
II Treated soda-lime
glass
Water Attack 100 or less 0.7
Over 100 0.2
III Soda-lime glass Powdered Glass All 8.5
NP General-purpose
soda-lime glass
Powdered Glass All 15.0
1  The description applies to containers of this type of glass usually available.
2  Size indicates the overflow capacity of the container.
Apparatus—
Autoclave— For these tests, use an autoclave capable of maintaining a temperature of 121 ± 2.0, 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.
Mortar and Pestle— Use a hardened-steel mortar and pestle, made according to the specifications in the accompanying illustration.
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Special Mortar and Pestle for Pulverizing Glass2
Other Equipment— Also required are 20.3-cm (8-inch) sieves made of stainless steel including the Nos. 20, 40, and 50 sieves along with the pan and cover (see Sizes of Standard Sieve Series in Range of Interest under Particle Size Distribution Estimation by Analytical Sieving 786), 250-mL 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.
Reagents—
High-Purity Water— The water used in these tests has a conductivity at 25, 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 µm.3 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 5 drops of indicator, does not require more than 0.020 mL of 0.020 N sodium hydroxide to effect the color change of the indicator, which should occur at a pH of 5.6.
Powdered Glass Test
Rinse thoroughly with Purified Water 6 or more containers selected at random, and dry them with a current of clean, dry air. Crush the containers into fragments about 25 mm 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 3 or 4 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, 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 5 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 seconds 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 minutes at 140, transfer the grains to a weighing bottle, and cool in a desiccator. Use the test specimen within 48 hours after drying.
Procedure— Transfer 10.00 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 90 for at least 24 hours or at 121 for 1 hour. 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 minutes. Close the vent cock, and adjust the temperature to 121, taking 19 to 23 minutes to reach the desired temperature. Hold the temperature at 121 ± 2.0 for 30 minutes, counting from the time this temperature is reached. Reduce the heat so that the autoclave cools and comes to atmospheric pressure in 38 to 46 minutes, 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 5 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 Table 2 for the type of glass concerned.
Water Attack at 121
Rinse thoroughly 3 or more containers, selected at random, twice 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 minutes instead of 30 minutes, and ending with “to prevent the formation of a vacuum.” Empty the contents from 1 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 5 drops of Methyl Red Solution, and titrate, while warm, with 0.020 N sulfuric acid. Complete the titration within 60 minutes 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 2 for the type of glass concerned.
Arsenic
Arsenic 211 Use as the Test Preparation 35 mL of the water from one Type I glass container or, in the case of smaller containers, 35 mL of the combined contents of several Type I glass containers, prepared as directed for Procedure under Water Attack at 121: the limit is 0.1 µg per g.

BIOLOGICAL TESTS—PLASTICS AND OTHER POLYMERS
Perform the in vitro biological tests according to the procedures set forth under Biological Reactivity Tests, In Vitro 87. Materials that meet the requirements of the in vitro tests are not required to undergo further testing. No plastic class designation is assigned to these materials. Materials that do not meet the requirements of the in vitro tests are not suitable for containers for drug products.
If a plastic class designation is needed for plastics and other polymers that meet the requirements under Biological Reactivity Tests, In Vitro 87, perform the appropriate in vivo tests specified for Classification of Plastics under Biological Reactivity Tests, In Vivo 88.

PHYSICOCHEMICAL TESTS—PLASTICS
The following tests, designed to determine physical and chemical properties of plastics and their extracts, are based on the extraction of the plastic material, and it is essential that the designated amount of the plastic be used. Also, the specified surface area must be available for extraction at the designated temperature.
Extracting Medium— Unless otherwise directed in a specific test below, use Purified Water (see monograph) as the extracting medium, maintained at a temperature of 70 during the extraction of the prepared Sample.
Apparatus— Use a water bath and the Extraction Containers as described under Biological Reactivity Tests, In Vivo 88.
Preparation of Apparatus— Proceed as directed in the first paragraph of Preparation of Apparatus under Biological Reactivity Tests, In Vivo 88. [NOTE—The containers and equipment need not be sterile.]
Procedure—
Preparation of Sample— From a homogeneous plastic specimen, use a portion, for each 20.0 mL of extracting medium, equivalent to 120 cm2 total surface area (both sides combined), and subdivide into strips approximately 3 mm in width and as near to 5 cm in length as is practical. Transfer the subdivided Sample to a glass-stoppered, 250-mL graduated cylinder of Type I glass, and add about 150 mL of Purified Water. Agitate for about 30 seconds, drain off and discard the liquid, and repeat with a second washing.
Transfer the prepared Sample to a suitable extraction flask, and add the required amount of Extracting Medium. Extract by heating in a water bath at the temperature specified for the Extracting Medium for 24 hours. Cool, but not below 20. Pipet 20 mL of the extract of the prepared Sample into a suitable container. Use this portion in the test for Buffering Capacity. Immediately decant the remaining extract into a suitably cleansed container, and seal.
Blank— Use Purified Water where a blank is specified in the following tests.
NONVOLATILE RESIDUE— Transfer, in suitable portions, 50.0 mL of the extract of the prepared Sample to a suitable, tared crucible (preferably a fused-silica crucible that has been acid-cleaned), and evaporate the volatile matter on a steam bath. Similarly evaporate 50.0 mL of the Blank in a second crucible. [NOTE—If an oily residue is expected, inspect the crucible repeatedly during the evaporation and drying period, and reduce the amount of heat if the oil tends to creep along the walls of the crucible.] Dry at 105 for 1 hour: the difference between the amounts obtained from the Sample and the Blank does not exceed 15 mg.
RESIDUE ON IGNITION 281[NOTE—It is not necessary to perform this test when the Nonvolatile Residue test result does not exceed 5 mg.] Proceed with the Nonvolatile Residue obtained from the Sample and from the Blank, using, if necessary, additional sulfuric acid but adding the same amount of sulfuric acid to each crucible: the difference between the amounts of residue on ignition obtained from the Sample and the Blank does not exceed 5 mg.
HEAVY METALS— Pipet 20 mL of the extract of the prepared Sample, filtered if necessary, into one of two matched 50-mL color-comparison tubes. Adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, using short-range pH paper as external indicator, dilute with water to about 35 mL, and mix.
Into the second color-comparison tube pipet 2 mL of Standard Lead Solution (see Heavy Metals 231), and add 20 mL of the Blank. Adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, using short-range pH paper as external indicator, dilute with water to about 35 mL, and mix. To each tube add 1.2 mL of thioacetamide-glycerin base TS and 2 mL of pH 3.5 Acetate Buffer (see Heavy Metals 231), dilute with water to 50 mL, and mix: any brown color produced within 10 minutes in the tube containing the extract of the prepared Sample does not exceed that in the tube containing the Standard Lead Solution, both tubes being viewed downward over a white surface (1 ppm in extract).
BUFFERING CAPACITY— Titrate the previously collected 20-mL portion of the extract of the prepared Sample potentiometrically to a pH of 7.0, using either 0.010 N hydrochloric acid or 0.010 N sodium hydroxide, as required. Treat a 20.0-mL portion of the Blank similarly: if the same titrant was required for both Sample and Blank, the difference between the two volumes is not greater than 10.0 mL; and if acid was required for either the Sample or the Blank and alkali for the other, the total of the two volumes required is not greater than 10.0 mL.

CONTAINERS FOR OPHTHALMICS—PLASTICS
Plastics for ophthalmics are composed of a mixture of homologous compounds, having a range of molecular weights. Such plastics frequently contain other substances such as residues from the polymerization process, plasticizers, stabilizers, antioxidants, pigments, and lubricants. Factors such as plastic 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.
Definition— For the purposes of this chapter, a container is that which holds the drug and is or may be in direct contact with the drug.
Biological Tests— Plastics and other polymers used for containers for ophthalmics meet the requirements set forth in the section Biological TestsPlastics and Other Polymers.

POLYETHYLENE CONTAINERS
The standards and tests provided in this section characterize high-density and low-density polyethylene containers that are interchangeably suitable for packaging dry oral dosage forms not meant for constitution into solution.
Where stability studies have been performed to establish the expiration date of a particular dry oral dosage form not meant for constitution into solution in a container meeting the requirements set forth herein for either high- or low-density polyethylene containers, then any other polyethylene container meeting the same sections of 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 identity, strength, quality, and purity of the dosage form are maintained throughout the expiration period.
Both high- and low-density polyethylene are long-chain polymers synthesized under controlled conditions of heat and pressure, with the aid of catalysts from not less than 85.0% ethylene and not less than 95.0% total olefins. The other olefin ingredients most frequently used are butene, hexene, and propylene. The ingredients used to manufacture the polyethylene, and those used in the fabrication of the containers, conform to the requirements in the applicable sections of the Code of Federal Regulations, Title 21.
High-density polyethylene and low-density polyethylene both have an IR absorption spectrum that is distinctive for polyethylene, and each possesses characteristic thermal properties. High-density polyethylene has a density between 0.941 and 0.965 g per cm3. Low-density polyethylene has a density between 0.850 and 0.940 g per cm3. The permeation properties of molded polyethylene containers may be altered when re-ground polymer is incorporated, depending upon the proportion of re-ground material in the final product. Other properties that may affect the suitability of polyethylene used in containers for packaging drugs are: oxygen and moisture permeability, modulus of elasticity, melt index, environmental stress crack resistance, and degree of crystallinity after molding. The requirements in this section are to be met when dry oral dosage forms, not meant for constitution into solution, are intended 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.4 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 multiple internal reflectance accessory. Taking care to avoid scratching the surfaces, wipe the specimens with dry paper or, if necessary, clean them 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 thin uniform films by exposing them to temperatures of about 177 under high pressures (15,000 psi or more).
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 adjustments 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 USP High-density Polyethylene RS or USP Low-density Polyethylene RS, similarly determined.
Thermal Analysis— Cut a section weighing about 12 mg, and place it in the test-specimen pan. Determine the thermogram under nitrogen at temperatures between 40 and 200 at a heating rate between 2 and 10 per minute followed by cooling at a rate between 2 and 10 per minute to 40, using equipment capable of performing the determinations described under Thermal Analysis 891.
High-Density Polyethylene— The thermogram of the specimen is similar to the thermogram of USP High-Density Polyethylene RS, similarly determined, and the temperatures of the endotherms and exotherms in the thermogram of the specimen do not differ from those of the standard by more than 6.0.
Low-Density Polyethylene— The thermogram of the specimen is similar to the thermogram of USP Low-Density Polyethylene RS, similarly determined, and the temperatures of the endotherms and exotherms in the thermogram of the specimen do not differ from those of the standard by more than 8.0.
Light Transmission— Polyethylene 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.5 Test the containers as described under Containers—Permeation 671: the high-density polyethylene containers so tested meet the requirements if the moisture permeability exceeds 10 mg per day per L in not more than 1 of the 10 test containers and exceeds 25 mg per day per L in none of them. The low-density polyethylene containers so tested meet the requirements if the moisture permeability exceeds 20 mg per day per L in not more than 1 of the 10 test containers and exceeds 30 mg per day per L in none of them.
Heavy Metals and Nonvolatile Residue— Prepare extracts of specimens for these tests as directed for Preparation of Sample in the Procedure under Physicochemical Tests—Plastics, except that for each 20.0 mL of Extracting Medium the portion shall be 60 cm2, regardless of thickness.
HEAVY METALS— Containers meet the requirements for Heavy Metals under Physicochemical Tests—Plastics.
NONVOLATILE RESIDUE— Proceed as directed for Nonvolatile Residue under Physicochemical Tests—Plastics, 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 12.0 mg when water maintained at a temperature of 70 is used as the extracting medium; does not exceed 75.0 mg when alcohol maintained at a temperature of 70 is used as the extracting medium; and does not exceed 100.0 mg for high-density polyethylene and does not exceed 350.0 mg for low-density polyethylene when hexanes maintained at a temperature of 50 are used as the extracting medium. Containers meet these requirements for Nonvolatile Residue for all of the above extracting media. [NOTE—Hexanes 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.]

POLYETHYLENE TEREPHTHALATE BOTTLES AND POLYETHYLENE TEREPHTHALATE G BOTTLES
The standards and tests provided in this section characterize polyethylene terephthalate (PET) and polyethylene terephthalate G (PETG) bottles that are interchangeably suitable for packaging liquid oral dosage forms.
Where stability studies have been performed to establish the expiration date of a particular liquid oral dosage form in a bottle meeting the requirements set forth herein for either PET or PETG bottles, any other PET or PETG bottle meeting these requirements may be similarly used to package such dosage form, provided that the appropriate stability programs are expanded to include the alternative bottle in order to assure that the identity, strength, quality, and purity of the dosage form are maintained throughout the expiration period.
The suitability of a specific PET or PETG bottle for use in the dispensing of a particular pharmaceutical liquid oral dosage form must be established by appropriate testing.
PET resins are long-chain crystalline polymers prepared by the condensation of ethylene glycol with dimethyl terephthalate or terephthalic acid. PET copolymer resins are prepared in a similar way, except that they may also contain a small amount of either isophthalic acid (not more than 3 mole percent) or 1,4-cyclohexanedimethanol (not more than 5 mole percent). Polymerization is conducted under controlled conditions of heat and vacuum, with the aid of catalysts and stabilizers.
PET copolymer resins have physical and spectral properties similar to PET and for practical purposes are treated as PET. The tests and specifications provided in this section to characterize PET resins and bottles apply also to PET copolymer resins and to bottles fabricated from them.
PET and PET copolymer resins generally exhibit a large degree of order in their molecular structure. As a result, they exhibit characteristic composition-dependent thermal behavior, including a glass transition temperature of about 76 and a melting temperature of about 250. These resins have a distinctive IR absorption spectrum that allows them to be distinguished from other plastic materials (e.g., polycarbonate, polystyrene, polyethylene, and PETG resins). PET and PET copolymer resins have a density between 1.3 and 1.4 g per cm3 and a minimum intrinsic viscosity of 0.7 dL per g, which corresponds to a number average molecular weight of about 23,000 daltons.
PETG resins are high molecular weight polymers prepared by the condensation of ethylene glycol with dimethyl terephthalate or terephthalic acid and 15 to 34 mole percent of 1,4-cyclohexanedimethanol. PETG resins are clear, amorphous polymers, having a glass transition temperature of about 81 and no crystalline melting point, as determined by differential scanning calorimetry. PETG resins have a distinctive IR absorption spectrum that allows them to be distinguished from other plastic materials, including PET. PETG resins have a density of approximately 1.27 g per cm3 and a minimum instrinsic viscosity of 0.65 dL per g, which corresponds to a number average molecular weight of about 16,000 daltons.
PET and PETG resins, and other ingredients used in the fabrication of these bottles, conform to the requirements in the applicable sections of the Code of Federal Regulations, Title 21, regarding use in contact with food and alcoholic beverages. PET and PETG resins do not contain any plasticizers, processing aids, or antioxidants. Colorants, if used in the manufacture of PET and PETG bottles, do not migrate into the contained liquid.
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.6 A KRS-5 crystal having a thickness of 2 mm and 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 bottle, and trim them as necessary to obtain segments that are convenient for mounting in the multiple internal reflectance accessory. Taking care to avoid scratching the surfaces, wipe the specimens with dry paper or, if necessary, clean them 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.
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 beams. (For a double-beam instrument, upon completing the adjustments in the accessory, attenuate the reference beam to permit full-scale deflection during the scanning of the specimen.) Determine the IR spectrum from 4000 to 400 cm1. The corrected spectrum of the specimen exhibits major absorption bands only at the same wavelengths as the spectrum of the USP Polyethylene Terephthalate RS, or the USP Polyethylene Terephthalate G RS, similarly determined.
Thermal Analysis— Cut a section weighing about 12 mg from the bottle, and place it in the test-specimen pan. Determine the thermogram under nitrogen, using the heating and cooling conditions as specified for the resin type and using equipment capable of performing the determinations as described under Thermal Analysis 891.
Polyethylene Terephthalate— Heat the specimen from room temperature to 280 at a heating rate of about 20 per minute. Hold the specimen at 280 for 1 minute. Quickly cool the specimen to room temperature, and reheat it to 280 at a heating rate of about 5 per minute. The thermogram of the specimen is similar to the thermogram of USP Polyethylene Terephthalate RS, similarly determined: the melting point (Tm) of the specimen does not differ from that of the Standard by more than 9.0, and the glass transition temperature (Tg) of the specimen does not differ from that of the Standard by more than 4.0.
Polyethylene Terephthalate G— Heat the specimen from room temperature to 120 at a heating rate of about 20 per minute. Hold the specimen at 120 for 1 minute. Quickly cool the specimen to room temperature, and reheat it to 120 at a heating rate of about 10 per minute. The thermogram of the specimen is similar to the thermogram of USP Polyethylene Terephthalate G RS, similarly determined: the glass transition temperature (Tg) of the specimen does not differ from that of the Standard by more than 6.0.
Light Transmission— PET and PETG bottles intended to provide protection from light meet the requirements under Light Transmission.
Water Vapor Permeation— [NOTE—Throughout the following procedure, determine the weights of bottles and closures, both as tare weights and weights of filled bottles, to the nearest 0.1 mg if the bottle volume is less than 200 mL; to the nearest mg if the bottle volume is 200 mL or more but less than 1000 mL; or to the nearest centigram (10 mg) if the bottle volume is 1000 mL or more.] Select 10 bottles of a uniform size and type, clean the sealing surfaces with a lint-free cloth, and close and open each bottle 30 times. Apply the closure firmly and uniformly each time the bottle is closed. Close screw-capped bottles with a torque that is within the range of tightness specified in the table provided under Containers—Permeation 671. Weigh each empty bottle and its closure. Fill ten bottles with water at 25 ± 2 until the meniscus is tangent to the top of the bottle opening. Record the weight of each bottle and its closure, and determine the average bottle volume, in L, taken by the following formula:
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where Woi is the total weight, in g, of bottle i and its closure, Wti is the tare weight, in g, of bottle i and its closure, and 9970 is the density of water at 25 times 10,000 (the number of bottles tested times the conversion factor for converting milliliters to liters).
Using a pipet, adjust the water level in the bottles to the fill point. Apply the closures using a torque that is within the range specified in the table provided under Containers—Permeation 671, and store the bottles at a temperature of 25 ± 2 and a relative humidity of 50 ± 2%. After 168 ± 1 hours (7 days), record the weight of the individual bottles. Return the bottles to storage for another 168 ± 1 hours. After the second 168 ± 1 hours, remove the bottles, record the weights of the individual bottles, and calculate the water vapor permeation rate, in mg per day per L, for each bottle taken by the formula:
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in which Wli is the weight, in mg, of bottle i at 14 days, Wfi is the weight, in mg, of bottle i at 7 days, 7 is the test time, in days, after the 7-day equilibration period, and Va is the average bottle volume, in L.
The bottles so tested meet the requirements and are tight containers if the water vapor permeation rate exceeds 100 mg per day per L in not more than 1 of the 10 test bottles and exceeds 200 mg per day per L in none of them.
Colorant Extraction— Select 3 test bottles. Cut a relatively flat portion from the side wall of one bottle, and trim it as necessary to fit the sample holder of the spectrophotometer. Obtain the visible spectrum of the side wall by scanning the portion of the visible spectrum from 350 to 700 nm. Determine, to the nearest 2 nm, the wavelength of maximum absorbance. Fill the remaining two test bottles, using 50% alcohol for PET bottles and 25% alcohol for PETG bottles. Fit the bottles with impervious seals, such as aluminum foil, and apply closures. Fill a glass bottle having the same capacity as that of the test bottles with the corresponding solvent, fit the bottle with an impervious seal, such as aluminum foil, and apply a closure. Incubate the test bottles and the glass bottle in a constant temperature room or in an oven at 49 for ten days. Remove the bottles, and allow them to equilibrate to room temperature. Concomitantly determine the absorbances of the test solutions in 5-cm cells at the wavelength of maximum absorbance (see Spectrophotometry and Light-Scattering 851), using the corresponding solvent from the glass bottle as the blank. The absorbance values so obtained are less than 0.01 for both test solutions.
Heavy Metals, Total Terephthaloyl Moieties, and Ethylene Glycol—
EXTRACTING MEDIA
Purified Water— (see monograph).
50 Percent Alcohol— Dilute 125 mL of alcohol with water to 238 mL, and mix.
25 Percent Alcohol— Dilute 125 mL of 50 Percent Alcohol with water to 250 mL, and mix.
n-Heptane.
PROCEDURE[NOTE—Use the 50 Percent Alcohol Extracting Medium with PET bottles. Use the 25 Percent Alcohol Extracting Medium with PETG bottles.] For each Extracting Medium, fill a sufficient number of test bottles to 90% of their nominal capacity to obtain not less than 30 mL of extract. Fill a corresponding number of glass bottles with Purified Water Extracting Medium, a corresponding number of glass bottles with 50 Percent Alcohol Extracting Medium or 25 Percent Alcohol Extracting Medium, and a corresponding number of glass bottles with n-Heptane Extracting Medium for use as Extracting Media blanks. Fit the bottles with impervious seals, such as aluminum foil, and apply closures. Incubate the test bottles and the glass bottles in a constant temperature room or in an oven at 49 for ten days. Remove the test bottles with the Extracting Media samples and the glass bottles with the Extracting Media blanks, and store them at room temperature. Do not transfer the Extracting Media samples to alternative storage vessels.
HEAVY METALS— Pipet 20 mL of the Purified Water extract of the test bottles, filtered if necessary, into one of two matched 50-mL color-comparison tubes, and retain the remaining Purified Water extract in the test bottles for use in the test for Ethylene Glycol. Adjust the extract with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, using short-range pH paper as an external indicator. Dilute with water to about 35 mL, and mix.
Into the second color-comparison tube, pipet 2 mL of freshly prepared (on day of use) Standard Lead Solution (see Heavy Metals 231), and add 20 mL of Purified Water. Adjust with 1 N acetic acid or 6 N ammonium hydroxide to a pH between 3.0 and 4.0, using short-range pH paper as an external indicator. Dilute with water to about 35 mL, and mix.
To each tube add 1.2 mL of thioacetamide-glycerin base TS and 2 mL of pH 3.5 Acetate Buffer (see Heavy Metals 231), dilute with water to 50 mL, and mix: any color produced within 10 minutes in the tube containing the Purified Water extract of the test bottles does not exceed that in the tube containing the Standard Lead Solution, both tubes being viewed downward over a white surface (1 ppm in extract).
Total Terephthaloyl Moieties Determine the absorbance of the 50 Percent Alcohol or 25 Percent Alcohol extract in a 1-cm cell at the wavelength of maximum absorbance at about 244 nm (see Spectrophotometry and Light-Scattering 851), using the corresponding Extracting Medium blank as the blank: the absorbance of the extract does not exceed 0.150, corresponding to not more than 1 ppm of total terephthaloyl moieties.
Determine the absorbance of the n-Heptane extract in a 1-cm cell at the wavelength of maximum absorbance at about 240 nm (see Spectrophotometry and Light-Scattering 851), using the n-Heptane Extracting Medium blank as the blank: the absorbance of the extract does not exceed 0.150, corresponding to not more than 1 ppm of total terephthaloyl moieties.
ETHYLENE GLYCOL
Periodic Acid Solution— Dissolve 125 mg of periodic acid in 10 mL of water.
Dilute Sulfuric Acid— To 50 mL of water add slowly and with constant stirring 50 mL of sulfuric acid, and allow to cool to room temperature.
Sodium Bisulfite Solution— Dissolve 0.1 g of sodium bisulfite in 10 mL of water. Use this solution within seven days.
Disodium Chromotropate Solution— Dissolve 100 mg of disodium chromotropate in 100 mL of sulfuric acid. Protect this solution from light, and use within seven days.
Standard Solution— Dissolve an accurately weighed quantity of ethylene glycol in water, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 1 µg per mL.
Test Solution— Use the Purified Water extract.
Blank— Use the Purified Water Extracting Medium blank.
Procedure— Transfer 1.0 mL of Standard Solution to a 10-mL volumetric flask. Transfer 1.0 mL of Test Solution to a second 10-mL volumetric flask. Transfer 1.0 mL of Purified Water Extracting Medium blank to a third 10-mL volumetric flask. To each of the three flasks, add 100 µL of Periodic Acid Solution, swirl to mix, and allow to stand for 60 minutes. Add 1.0 mL of Sodium Bisulfite Solution to each flask, and mix. Add 100 µL of Disodium Chromotropate Solution to each flask, and mix. [NOTE—All solutions should be analyzed within one hour after addition of the Disodium Chromotropate Solution.] Cautiously add 6 mL of sulfuric acid to each flask, mix, and allow the solutions to cool to room temperature. [Caution—Dilution of sulfuric acid produces substantial heat and can cause the solution to boil. Perform this addition carefully. Sulfur dioxide gas will be evolved. Use of a fume hood is recommended. ] Dilute each solution with Dilute sulfuric acid to volume, and mix. Concomitantly determine the absorbances of the solutions from the Standard Solution and the Test Solution in 1-cm cells at the wavelength of maximum absorbance at about 575 nm (see Spectrophotometry and Light-Scattering 851), using the solution from the Purified Water Extracting Medium blank as the blank: the absorbance of the solution from the Test solution does not exceed that of the solution from the Standard solution, corresponding to not more than 1 ppm of ethylene glycol.

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 Containers—Permeation 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 Tests—Plastics, except that for each 20 mL of Extracting Medium the portion shall be 60 cm2, regardless of thickness.
HEAVY METALS— Containers meet the requirements for Heavy Metals under Physicochemical Tests—Plastics.
NONVOLATILE RESIDUE— Proceed as directed for Nonvolatile Residue under Physicochemical Tests—Plastics, 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. [NOTE—Hexanes 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 Tests—Plastics. Containers meet the requirements for Buffering Capacity under Physicochemical Tests—Plastics.

REPACKAGING INTO SINGLE-UNIT CONTAINERS AND UNIT-DOSE CONTAINERS FOR NONSTERILE SOLID AND LIQUID DOSAGE FORMS
An official dosage form is required to bear on its label an expiration date assigned for the particular formulation and package of the article. This date limits the time during which the product may be dispensed or used. Because the expiration date stated on the manufacturer's or distributor's package has been determined for the drug in that particular package and is not intended to be applicable to the product where it has been repackaged in a different container, repackaged drugs dispensed pursuant to a prescription are exempt from this expiration date labeling requirement. It is necessary, therefore, that other precautions be taken by the dispenser to preserve the strength, quality, and purity of drugs that are repackaged for ultimate distribution or sale to patients.
The following guidelines and requirements are applicable where official dosage forms are repackaged into single-unit or unit-dose containers or mnemonic packs for dispensing pursuant to prescription.
Labeling— It is the responsibility of the dispenser, taking into account the nature of the drug repackaged, any packaging and beyond-use dating information in the manufacturer's product labeling, the characteristics of the containers, and the storage conditions to which the article may be subjected, to place a suitable beyond-use date on the label. Repackaged dosage forms must bear on their labels beyond-use dates as determined from information in the product labeling. Each single-unit or unit-dose container bears a separate label, unless the device holding the unit-dose form does not allow for the removal or separation of the intact single-unit or unit-dose container therefrom.
Storage— Store the repackaged article in a humidity-controlled environment and at the temperature specified in the individual monograph or in the product labeling. Where no temperature or humidity is specified in the monograph or in the labeling of the product, controlled room temperature and a relative humidity corresponding to 75% at 23 are not to be exceeded during repackaging or storage.
A refrigerator or freezer shall not be considered to be a humidity-controlled environment, and drugs that are to be stored at a cold temperature in a refrigerator or freezer shall be placed within an outer container that meets the monograph requirements for the drug contained therein.
Reprocessing— Reprocessing of repackaged unit-dose containers (i.e., removing dosage unit from one unit-dose container and placing dosage unit into another unit-dose container) shall not be done. However, reprocessing of the secondary package (e.g., removing the blister card from the cardboard carrier and placing the blister card into another cardboard carrier) is allowed provided that the original beyond-use date is maintained.

CUSTOMIZED PATIENT MEDICATION PACKAGES
In lieu of dispensing two or more prescribed drug products in separate containers, a pharmacist may, with the consent of the patient, the patient's caregiver, or a prescriber, provide a customized patient medication package (patient med pak).7
A patient med pak is a package prepared by a pharmacist for a specific patient comprising a series of containers and containing two or more prescribed solid oral dosage forms. The patient med pak is so designed or each container is so labeled as to indicate the day and time, or period of time, that the contents within each container are to be taken.
It is the responsibility of the dispenser to instruct the patient or caregiver on the use of the patient med pak.
Label— The patient med pak shall bear a label stating:
  1. the name of the patient;
  2. a serial number for the patient med pak itself and a separate identifying serial number for each of the prescription orders for each of the drug products contained therein;
  3. the name, strength, physical description or identification, and total quantity of each drug product contained therein;
  4. the directions for use and cautionary statements, if any, contained in the prescription order for each drug product therein;
  5. any storage instructions or cautionary statements required by the official compendia;
  6. the name of the prescriber of each drug product;
  7. the date of preparation of the patient med pak and the beyond-use date or period of time assigned to the patient med pak (such beyond-use date or period of time shall be not longer than the shortest recommended beyond-use date for any dosage form included therein or not longer than 60 days from the date of preparation of the patient med pak and shall not exceed the shortest expiration date on the original manufacturer's bulk containers for the dosage forms included therein); alternatively, the package label shall state the date of the prescription(s) or the date of preparation of the patient med pak, provided the package is accompanied by a record indicating the start date and the beyond-use date;
  8. the name, address, and telephone number of the dispenser (and the dispenser's registration number where necessary); and
  9. any other information, statements, or warnings required for any of the drug products contained therein.
If the patient med pak allows for the removal or separation of the intact containers therefrom, each individual container shall bear a label identifying each of the drug products contained therein.
Labeling— The patient med pak shall be accompanied by a patient package insert, in the event that any medication therein is required to be dispensed with such insert as accompanying labeling. Alternatively, such required information may be incorporated into a single, overall educational insert provided by the pharmacist for the total patient med pak.
Packaging— In the absence of more stringent packaging requirements for any of the drug products contained therein, each container of the patient med pak shall comply with the moisture permeation requirements for a Class B single-unit or unit-dose container (see Containers—Permeation 671). Each container shall be either not reclosable or so designed as to show evidence of having been opened.
Guidelines— It is the responsibility of the dispenser, when preparing a patient med pak, to take into account any applicable compendial requirements or guidelines and the physical and chemical compatibility of the dosage forms placed within each container, as well as any therapeutic incompatibilities that may attend the simultaneous administration of the medications. In this regard, pharmacists are encouraged to report to USP headquarters any observed or reported incompatibilities. Once a medication has been placed in a patient med pak with another solid dosage form, it may not be returned to stock, redistributed, or resold if unused.
Recordkeeping— In addition to any individual prescription filing requirements, a record of each patient med pak shall be made and filed. Each record shall contain, as a minimum:
  1. the name and address of the patient;
  2. the serial number of the prescription order for each drug product contained therein;
  3. the name of the manufacturer or labeler and lot number for each drug product contained therein;
  4. information identifying or describing the design, characteristics, or specifications of the patient med pak sufficient to allow subsequent preparation of an identical patient med pak for the patient;
  5. the date of preparation of the patient med pak and the beyond-use date that was assigned;
  6. any special labeling instructions; and
  7. the name or initials of the pharmacist who prepared the patient med pak.

1  For further detail regarding apparatus and procedures, reference may be made to the following publications of the American Society for Testing and Materials, 100 Barr Harbor Drive, West Conshohocken, PA19428-2959: “Standard Method of Test for Haze and Luminous Transmittance of Transparent Plastics,” ASTM Designation D-1003-61; “Tentative Method of Test for Luminous Reflectance, Transmittance, and Color of Materials,” ASTM E 308-66.
2  A suitable mortar and pestle is available (catalog No. H-17280) from Humboldt Manufacturing Co., 7300 West Agatite, Norridge, Chicago, IL 60656.
3  A suitable nuclear-grade resin mixture of the strong acid cation exchanger in the hydrogen form and the strong base anion exchanger in the hydroxide form, with a one-to-one cation to anion equivalence ratio, is available from the Millipore Corp., Bedford, MA 01730; Barnstead Co., 225 Rivermoor St., Boston, MA 02132; Illinois Water Treatment Co., 840 Cedar St., Rockford, IL 61105; and Vaponics, Inc., 200 Cordage Park, Plymouth, MA 02360.
A suitable in-line filter is available from the Millipore Corp.; Gelman Instrument Co., 600 S. Wagner Rd., Ann Arbor, MI 48106; and Schleicher and Schuell, Inc., 540 Washington St., Keene, NH 10003.
4  The multiple internal reflectance accessory and KRS-5 plate are available from several sources, including Beckman Instruments, Inc., 2500 Harbor Blvd., Fullerton, CA 92634, and from Perkin Elmer Corp., Main Ave., Norwalk, CT 06856.
5  A suitable laminate for sealing has as the container contact layer polyethylene of not less than 0.025 mm (0.001 inch) and a second layer of aluminum foil of not less than 0.018 mm (0.0007 inch), with additional layers of suitable backing materials. A suitable seal can be obtained also by using glass plates and a sealing wax consisting of 60% of refined amorphous wax and 40% of refined crystalline paraffin wax.
6  The multiple internal reflectance accessory and KRS-5 plate are available from several sources, including Beckman Instruments, Inc., 2500 Harbor Boulevard, Fullerton, CA 92634, and from Perkin Elmer Corporation, 761 Main Ave., Norwalk, CT 06859-01560.
7  It should be noted that there is no special exemption for patient med paks from the requirements of the Poison Prevention Packaging Act. Thus the patient med pak, if it does not meet child-resistant standards, shall be placed in an outer package that does comply, or the necessary consent of the purchaser or physician, to dispense in a container not intended to be child-resistant, shall be obtained.

Auxiliary Information—
Staff Liaison : Desmond G. Hunt, Ph.D., Senior Scientific Associate
Expert Committee : (PS05) Packaging and Storage 05
USP29–NF24 Page 2655
Pharmacopeial Forum : Volume No. 29(2) Page 490
Phone Number : 1-301-816-8341