ASTM D7709-12(2017)

NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: D7709 − 12 (Reapproved 2017)
Standard Test Methods for
Measuring Water Vapor Transmission Rate (WVTR) of
Pharmaceutical Bottles and Blisters
This standard is issued under the fixed designation D7709; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.7 The test methods in this standard were developed
specifically for pharmaceutical bottles and blisters as closed
1.1 The three test methods described herein are for mea-
container-closure systems. The experiment from which the
surement of water vapor transmission rates (WVTRs) of
methods were developed provided an inter-laboratory study
high-barrier multiple-unit containers (bottles), high-barrier
from which the precision and bias statement was written. The
single-unit containers (blisters), and quasi-barrier single-unit
packages in the study were small bottles and blisters used
containers used for packaging pharmaceutical products. The
regularly for pharmaceutical solid oral dosage forms.
containers are tested closed and sealed. These test methods can
be used for all consumer-sized primary containers and bulk 1.8 In spite of the specific nature of their application, the test
primary containers of a size limited only by the dimensions of methods in this standard should be suitable for other pharma-
the equipment and the weighing capacity and sensitivity of the ceutical packages and most types and sizes of other consumer
balance. packages.
1.2 These test methods are intended to be of sufficient 1.9 The values stated in SI units are to be regarded as the
sensitivity and precision to allow clear discrimination among standard. No other units of measurement are included in this
the levels of barrier packages currently available for pharma- standard. The units of measure for bottles are milligrams per
ceutical products. bottle per day (mg/bottle-day) and for blisters, milligrams per
blister cavity per day (mg/cavity-day). These units may be used
1.3 There are three methods: Method A is for bottles,
for both standard and referee testing.
Method B is for formed barrier blisters, and Method C is for
1.10 This standard does not purport to address all of the
formed quasi-barrier blisters. Methods B and C can be adapted
safety concerns, if any, associated with its use. It is the
for use with flexible pouches.
responsibility of the user of this standard to establish appro-
1.4 These test methods use gravimetric measurement to
priate safety, health and environmental practices and deter-
determine the rate of weight gain as a result of water vapor
mine the applicability of regulatory limitations prior to use.
transmission into the package and subsequent uptake by a
1.11 This international standard was developed in accor-
desiccant enclosed within the package. The packages are
dance with internationally recognized principles on standard-
exposed to environments typical of those used for accelerated
ization established in the Decision on Principles for the
stability testing of drug products in the package (typically
Development of International Standards, Guides and Recom-
40 °C ⁄75 % relative humidity [RH]).
mendations issued by the World Trade Organization Technical
1.5 For these methods, balance sensitivity, amount of
Barriers to Trade (TBT) Committee.
desiccant, number of blisters per test unit, and weighing
frequency were developed in an experiment based on Test
2. Referenced Documents
Methods E96/E96M.
2.1 ASTM Standards:
1.6 Test Methods E96/E96M gives specific instruction on
E96/E96M Test Methods for Water Vapor Transmission of
the interactions among weighing frequency, number of data
Materials
points necessary to establish steady state, minimum weight
gain in a weighing period, and balance sensitivity.
3. Terminology
3.1 Definitions:
These test methods are under the jurisdiction of ASTM Committee F02 on
Primary Barrier Packaging and is the direct responsibility of Subcommittee F02.10
on Permeation. For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Current edition approved Aug. 1, 2017. Published August 2017. Originally contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
approved in 2011. Last previous edition approved in 2012 as D7709 – 12. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/D7709-12R17. the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
D7709 − 12 (2017)
3.1.1 barrier blister, n—blister made from high-barrier containers (or cards). The desiccant-filled blister card is stored
material, formed and sealed so that the water vapor transmis- in an environment at 40 °C ⁄75 % RH. The card of desiccant
sion rate (WVTR) (when tested at 40 °C ⁄75 % RH) is less than filled blisters is weighed at prescribed time intervals until
1.0 mg/cavity-day. steady-state weight gain is obtained. Once steady-state is
obtained, the blister cards are weighed at five consecutive time
3.1.2 blister, n—formed, lidded and sealed plastic dome that
points.
contains the solid oral product (usually one unit).
3.1.2.1 Discussion—Synonymous with cavity.
4.3 WVTR for Method A or B is calculated using linear
regression of the weight versus time. The number of blisters
3.1.3 card, n—contiguous group of blisters formed and
tested depends on the barrier characteristics of the material, the
sealed with lid in place.
size of the blister, and the sensitivity of the balance used in the
3.1.3.1 Discussion—The card is a production geometry that
test.
is a convenient quantity for a dosage regimen. The number of
blisters per card commonly ranges from one to ten but may be
4.4 4.4 In Method C for quasi-barrier blisters, desiccant is
more. From a marketing and production point of view, the card
placed in the blister and the lid material is sealed in place using
is the basic, irreducible number of blisters in a market or
equipment that is capable of correctly filling and sealing the
clinical trial package. The blister card may sometimes be
containers (or cards). The desiccant-filled blister card is stored
referred to as the container.
in an environment at 40 °C ⁄75 % RH. The desiccant-filled
blister card is weighed at zero time and 48 h (two days). At this
3.1.4 cavity, n—see blister.
time, the difference in weight (the weight gain) in mg/cavity-
3.1.5 container, n—(1) bottle that contains multiple units of
day is taken as the WVTR. The number of blisters tested
drug product, or (2) a card of blisters formed and sealed with
depends on the barrier characteristics of the material, the size
lid.
of the blister, and the sensitivity of the balance used in the test.
3.1.6 quasi-barrier blister, n—blister made from low-barrier
NOTE 1—For this test method, the requirement of five consecutive
materials formed and sealed so that the WVTR (when tested at
weighings is waived because the desiccant quickly becomes saturated
40 °C ⁄75 % RH) is greater than 1.0 mg/cavity-day.
when packed in a quasi-barrier package and stored at 40 °C ⁄75 % RH.
3.1.6.1 Discussion—An example of this is 250 µm (10 mil)
During development of this test method, it appeared that after the second
poly(vinyl chloride) (PVC) formed into size zero blisters and day the weight gain displayed a curvilinear profile typical of approaching
saturation of the desiccant. To obtain five weighings within two days is an
sealed with aluminum foil lid.
unwieldy process and is likely to lack precision.
3.1.7 test specimen (or specimen), n—(1) for bottles, the
bottle is the test specimen and (2) for blisters, the blister card 5. Significance and Use
is the test specimen.
5.1 The purpose of these test methods is to obtain reliable
3.1.7.1 Discussion—For blisters, more than one card (or
values for WVTR that can be used to discriminate among
specimen) may be grouped into a test unit for conducting the
barrier packages for pharmaceutical products. These test meth-
test.
ods will establish a WVTR value that represents the water
3.1.8 test unit, n—(1) for bottles, the bottle is the test unit as
vapor transmission of the container closure system being
well as being the test specimen and (2) for blisters, the test unit evaluated. They are intended for use in evaluating or
is a group of test specimens (cards) processed together for
comparing, or both, the water vapor barrier performance of
temperature and humidity exposure and weighing at each time alternative packages for use in packaging of pharmaceutical
point.
products.
3.1.8.1 Discussion—The purpose of the test unit for blisters
5.2 While these methods were developed for a specific,
is to gain the advantage of additive weight gain resulting from
limited application, they should be suitable for most types and
more blisters than are on a single card. Detailed discussion of
sizes of consumer packages.
this point is available in Test Methods E96/E96M. The term
test unit when applied to bottles is simply to maintain congru-
6. Apparatus
ence of naming among the three test methods.
6.1 For weighing the test units in Method A, use a balance
that has sufficient capacity to weigh the total of bottle, cap, and
4. Summary of Test Method
desiccant throughout the period of the test. The balance shall
4.1 In Method A for bottles, desiccant is placed in the bottle
have sensitivity adequate to measure small differences in
which is then closed in the normal manner including any weight from one time point to the next. The balance sensitivity
membrane (tamper-evident or otherwise) sealed in place. The
shall be smaller than 5 % of the differences in weight from one
desiccant-filled bottle is stored in an environment at 40 °C ⁄75 time point to the next. (For example, during development of
% RH. The desiccant-filled bottle is weighed at prescribed time
this test method, a balance with capacity of 110 g and
intervals until steady-state weight gain is obtained. Once sensitivity of 0.1 mg was found to be acceptable for a 60 CC
steady state is obtained, the bottles are weighed at five
bottle.)
consecutive time points.
6.2 For weighing the test specimens in Methods B and C,
4.2 In Method B for barrier blisters, desiccant is placed in use a balance that has sufficient capacity to weigh the closed,
the blister and the lid material is sealed in place using sealed blister test unit throughout the period of use. The
equipment that is capable of filling and properly sealing the balance shall have sensitivity adequate to measure small
D7709 − 12 (2017)
TABLE 1 Closing Torque for Screw-Type Containers
differences in weight from one time interval to the next. The
balance sensitivity shall be smaller than 5 % of the differences Suggested Tightness
Suggested Tightness
Closure Range with Manually
in weight from one time interval to the next. For example,
Range with Manually
A
Diameter, mm Applied Torque, in. ·
Applied Torque, N · m
during development of this method, a balance with capacity of
lbf
8 0.56 5
110 g and sensitivity of 0.1 mg was found to be acceptable.
10 0.68 6
Test Methods B and C may require that the blister cards
13 0.90 8
(containers) be bundled in multiples to achieve periodic weight
15 0.56 – 1.02 5 – 9
gains of sufficient magnitude to use the balance sensitivity. 18 0.79 – 1.13 7 – 10
20 0.90 – 1.36 8 – 12
When so bundled, these cards are called test units. Test
22 1.02 – 1.58 9 – 14
Methods E96/E96M specify that the weight gain in each
24 1.13 – 2.03 10 – 18
28 1.36 – 2.37 12 – 21
weighing period shall be 20 times the sensitivity of the balance.
30 1.47 – 2.60 13 – 23
6.3 For exposure of packages to the test environment for
33 1.69 – 2.82 15 – 25
38 1.92 – 2.94 17 – 26
Methods A, B, and C, use a chamber capable of maintaining 40
43 1.92 – 3.05 17 – 27
6 2 °C and 75 6 5 % RH. The humidification should be
48 2.15 – 3.39 19 – 30
achieved with de-ionized water, or equivalent means, to limit
53 2.37 – 3.39 21 – 30
58 2.60 – 4.52 23 – 40
contamination from water impurities.
63 2.82 – 4.86 25 – 43
66 2.94 – 5.08 26 – 45
7. Reagents and Materials
A
For a closure having diameter between two diameters listed, use the torque range
7.1 Purity of Reagents—Reagent-grade chemicals shall be
for the next larger diameter.
used in all tests. Unless otherwise indicated, it is intended that
all reagents conform to the specifications of the Committee of
Analytical Reagents of the American Chemical Society where
such specifications are available. Other grades may be used,
bottles for preparation at the time of testing. The bottles and
provided it is first ascertained that the reagent is of sufficiently
closures should be stored such that they will not be damaged;
high purity to permit its use without lessening the accuracy of
particularly the mating surfaces of bottle and closure. Prepare
the determination.
the test specimens by filling each bottle ⁄3 with desiccant then
7.2 Desiccant for Method A—During development of close the container in the appropriate manner as quickly as
Method A, anhydrous calcium chloride in granular form was
possible, including any membrane seal (tamper-evident or
used as the desiccant. Other desiccants may be suitable; for otherwise), if appropriate. Filling of bottles shall be done in a
example, a molecular sieve or silica gel. If calcium chloride in
low-humidity atmosphere (as low as possible, but not greater
any form, including anhydrous, is used it shall be pre-dried at
than 50 % RH). Close screw caps in accordance with the torque
1 1
215 6 5 °C for 7 ⁄4 6 ⁄4 h to ensure that any hexahydrate
recommendations in Table 1.
present is fully converted to the anhydrate. Cool the desiccant
8.2 Methods B and C (Blisters)—Fill with pre-dried desic-
in a desiccator for at least 2 h before use.
cant and seal the blisters on equipment that is capable of
NOTE 2—It has been shown that anhydrous calcium chloride may
correctly filling and sealing the market or clinical trial package.
contain calcium hexahydrate, which loses water only when the tempera-
The desiccant tablet should fill the cavity, but for practical
ture reaches 200 °C.
considerations, multiple fragments may be used. If fragments
7.3 Desiccant for Methods B and C—During development
are used, the total weight of desiccant shall be enough to meet
of Method B, silica gel was used as the desiccant. It was used
the quantity required to avoid partial saturation of the desiccant
in a molded form to fit the size and shape of the blister used.
before completion o
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