ASTM D7709-11
(Test Method)Standard Test Methods for Measuring Water Vapor Transmission Rate (WVTR) of Pharmaceutical Bottles and Blisters
Standard Test Methods for Measuring Water Vapor Transmission Rate (WVTR) of Pharmaceutical Bottles and Blisters
SIGNIFICANCE AND USE
The purpose of these test methods is to obtain reliable values for WVTR that can be used to discriminate among barrier packages for pharmaceutical products. These test methods will establish a WVTR value that represents the water vapor transmission of the container closure system being evaluated. They are intended for use in evaluating or comparing, or both, the water vapor barrier performance of alternative packages for use in packaging of pharmaceutical products.
While these methods were developed for a specific, limited application, they should be suitable for most types and sizes of consumer packages.
SCOPE
1.1 The three test methods described herein are for measurement of water vapor transmission rates (WVTRs) of high-barrier multiple-unit containers (bottles), high-barrier single-unit containers (blisters), and quasi-barrier single-unit containers used for packaging pharmaceutical products. The containers are tested closed and sealed. These test methods can be used for all consumer-sized primary containers and bulk primary containers of a size limited only by the dimensions of the equipment and the weighing capacity and sensitivity of the balance.
1.2 These test methods are intended to be of sufficient sensitivity and precision to allow clear discrimination among the levels of barrier packages currently available for pharmaceutical products.
1.3 There are three methods: Method A is for bottles, Method B is for formed barrier blisters, and Method C is for formed quasi-barrier blisters. Methods B and C can be adapted for use with flexible pouches.
1.4 These test methods use gravimetric measurement to determine the rate of weight gain as a result of water vapor transmission into the package and subsequent uptake by a desiccant enclosed within the package. The packages are exposed to environments typical of those used for accelerated stability testing of drug products in the package (typically 40°C/75 % relative humidity [RH]).
1.5 For these methods, balance sensitivity, amount of desiccant, number of blisters per test unit, and weighing frequency were developed in an experiment based on Test Methods E96/E96M.
1.6 Test Methods E96/E96M gives specific instruction on the interactions among weighing frequency, number of data points necessary to establish steady state, minimum weight gain in a weighing period, and balance sensitivity.
1.7 The test methods in this standard were developed specifically for pharmaceutical bottles and blisters as closed container-closure systems. The experiment from which the methods were developed provided an inter-laboratory study from which the precision and bias statement was written. The packages in the study were small bottles and blisters used regularly for pharmaceutical solid oral dosage forms.
1.8 In spite of the specific nature of their application, the test methods in this standard should be suitable for other pharmaceutical packages and most types and sizes of other consumer packages.
1.9 The values stated in SI units are to be regarded as the standard. No other units of measurement are included in this standard. The units of measure for bottles are milligrams per bottle per day (mg/bottle-day) and for blisters, milligrams per blister cavity per day (mg/cavity-day). These units may be used for both standard and referee testing.
1.10 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
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Designation:D7709–11
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 methods were developed provided an inter-laboratory study
from which the precision and bias statement was written. The
1.1 The three test methods described herein are for mea-
packages in the study were small bottles and blisters used
surement of water vapor transmission rates (WVTRs) of
regularly for pharmaceutical solid oral dosage forms.
high-barrier multiple-unit containers (bottles), high-barrier
1.8 Inspiteofthespecificnatureoftheirapplication,thetest
single-unit containers (blisters), and quasi-barrier single-unit
methods in this standard should be suitable for other pharma-
containers used for packaging pharmaceutical products. The
ceutical packages and most types and sizes of other consumer
containers are tested closed and sealed.These test methods can
packages.
be used for all consumer-sized primary containers and bulk
1.9 The values stated in SI units are to be regarded as the
primary containers of a size limited only by the dimensions of
standard. No other units of measurement are included in this
the equipment and the weighing capacity and sensitivity of the
standard. The units of measure for bottles are milligrams per
balance.
bottle per day (mg/bottle-day) and for blisters, milligrams per
1.2 These test methods are intended to be of sufficient
blistercavityperday(mg/cavity-day).Theseunitsmaybeused
sensitivity and precision to allow clear discrimination among
for both standard and referee testing.
the levels of barrier packages currently available for pharma-
1.10 This standard does not purport to address all of the
ceutical products.
safety concerns, if any, associated with its use. It is the
1.3 There are three methods: Method A is for bottles,
responsibility of the user of this standard to establish appro-
Method B is for formed barrier blisters, and Method C is for
priate safety and health practices and determine the applica-
formed quasi-barrier blisters. Methods B and C can be adapted
bility of regulatory limitations prior to use.
for use with flexible pouches.
1.4 These test methods use gravimetric measurement to
2. Referenced Documents
determine the rate of weight gain as a result of water vapor
2.1 ASTM Standards:
transmission into the package and subsequent uptake by a
E96/E96M Test Methods for Water Vapor Transmission of
desiccant enclosed within the package. The packages are
Materials
exposed to environments typical of those used for accelerated
stability testing of drug products in the package (typically
3. Terminology
40°C/75 % relative humidity [RH]).
3.1 Definitions:
1.5 For these methods, balance sensitivity, amount of des-
3.1.1 barrier blister, n—blister made from high-barrier
iccant, number of blisters per test unit, and weighing frequency
material, formed and sealed so that the water vapor transmis-
were developed in an experiment based on Test Methods
sion rate (WVTR) (when tested at 40°C/75 % RH) is less than
E96/E96M.
1.0 mg/cavity-day.
1.6 Test Methods E96/E96M gives specific instruction on
3.1.2 blister, n—formed, lidded and sealed plastic dome
the interactions among weighing frequency, number of data
that contains the solid oral product (usually one unit).
points necessary to establish steady state, minimum weight
3.1.2.1 Discussion—Synonymous with cavity.
gain in a weighing period, and balance sensitivity.
3.1.3 card, n—contiguous group of blisters formed and
1.7 The test methods in this standard were developed
sealed with lid in place.
specifically for pharmaceutical bottles and blisters as closed
3.1.3.1 Discussion—The card is a production geometry that
container-closure systems. The experiment from which the
is a convenient quantity for a dosage regimen. The number of
This test method is under the jurisdiction of ASTM Committee D10 on
Packaging and is the direct responsibility of Subcommittee D10.32 on Consumer, For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Pharmaceutical and Medical Packaging. contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Current edition approved April 1, 2011. Published April 2011. DOI: 10.1520/ Standards volume information, refer to the standard’s Document Summary page on
D7709-11. the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
D7709–11
blisters per card commonly ranges from one to ten but may be containers (or cards). The desiccant-filled blister card is stored
more. From a marketing and production point of view, the card in an environment at 40°C/75 % RH. The desiccant-filled
is the basic, irreducible number of blisters in a market or blister card is weighed at zero time and 48 h (two days).At this
clinical trial package. The blister card may sometimes be time, the difference in weight (the weight gain) in mg/cavity-
referred to as the container. day is taken as the WVTR. The number of blisters tested
3.1.4 cavity, n—see blister. depends on the barrier characteristics of the material, the size
3.1.5 container, n—(1) bottle that contains multiple units of of the blister, and the sensitivity of the balance used in the test.
drug product, or (2) a card of blisters formed and sealed with
NOTE 1—For this test method, the requirement of five consecutive
lid.
weighings is waived because the desiccant quickly becomes saturated
3.1.6 quasi-barrier blister, n—blister made from low-
when packed in a quasi-barrier package and stored at 40°C/75 % RH.
barrier materials formed and sealed so that the WVTR (when
During development of this test method, it appeared that after the second
day the weight gain displayed a curvilinear profile typical of approaching
tested at 40°C/75 % RH) is greater than 1.0 mg/cavity-day.
saturation of the desiccant.To obtain five weighings within two days is an
3.1.6.1 Discussion—An example of this is 250 µm (10 mil)
unwieldy process and is likely to lack precision.
poly(vinyl chloride) (PVC) formed into size zero blisters and
sealed with aluminum foil lid.
5. Significance and Use
3.1.7 test specimen (or specimen), n—(1) for bottles, the
5.1 The purpose of these test methods is to obtain reliable
bottle is the test specimen and (2) for blisters, the blister card
values for WVTR that can be used to discriminate among
is the test specimen.
barrier packages for pharmaceutical products. These test meth-
3.1.7.1 Discussion—For blisters, more than one card (or
ods will establish a WVTR value that represents the water
specimen) may be grouped into a test unit for conducting the
vapor transmission of the container closure system being
test.
evaluated. They are intended for use in evaluating or compar-
3.1.8 test unit, n—(1) for bottles, the bottle is the test unit as
ing, or both, the water vapor barrier performance of alternative
well as being the test specimen and (2) for blisters, the test unit
packages for use in packaging of pharmaceutical products.
is a group of test specimens (cards) processed together for
5.2 While these methods were developed for a specific,
temperature and humidity exposure and weighing at each time
limited application, they should be suitable for most types and
point.
sizes of consumer packages.
3.1.8.1 Discussion—The purpose of the test unit for blisters
is to gain the advantage of additive weight gain resulting from
6. Apparatus
more blisters than are on a single card. Detailed discussion of
6.1 For weighing the test units in Method A, use a balance
this point is available in Test Methods E96/E96M. The term
that has sufficient capacity to weigh the total of bottle, cap, and
test unit when applied to bottles is simply to maintain congru-
desiccant throughout the period of the test. The balance shall
ence of naming among the three test methods.
have sensitivity adequate to measure small differences in
4. Summary of Test Method
weight from one time point to the next. The balance sensitivity
4.1 In MethodAfor bottles, desiccant is placed in the bottle shall be smaller than5%ofthedifferences in weight from one
which is then closed in the normal manner including any time point to the next. (For example, during development of
membrane (tamper-evident or otherwise) sealed in place. The this test method, a balance with capacity of 110 g and
desiccant-filledbottleisstoredinanenvironmentat40°C/75% sensitivity of 0.1 mg was found to be acceptable for a 60 CC
RH. The desiccant-filled bottle is weighed at prescribed time bottle.)
intervals until steady-state weight gain is obtained. Once 6.2 For weighing the test specimens in Methods B and C,
steady state is obtained, the bottles are weighed at five use a balance that has sufficient capacity to weigh the closed,
consecutive time points. sealed blister test unit throughout the period of use. The
balance shall have sensitivity adequate to measure small
4.2 In Method B for barrier blisters, desiccant is placed in
the blister and the lid material is sealed in place using differences in weight from one time interval to the next. The
balance sensitivity shall be smaller than5%ofthedifferences
equipment that is capable of filling and properly sealing the
containers (or cards). The desiccant-filled blister card is stored in weight from one time interval to the next. (For example,
in an environment at 40°C/75 % RH. The card of desiccant during development of this method, a balance with capacity of
filled blisters is weighed at prescribed time intervals until 110 g and sensitivity of 0.1 mg was found to be acceptable.
steady-state weight gain is obtained. Once steady-state is Test Methods B and C may require that the blister cards
obtained, the blister cards are weighed at five consecutive time (containers) be bundled in multiples to achieve periodic weight
points. gains of sufficient magnitude to use the balance sensitivity.
4.3 WVTR for Methods A or B is calculated using linear When so bundled, these cards are called test units. Test
regression of the weight versus time. The number of blisters Methods E96/E96M specify that the weight gain in each
tested depends on the barrier characteristics of the material, the weighingperiodshallbe20timesthesensitivityofthebalance.
size of the blister, and the sensitivity of the balance used in the 6.3 For exposure of packages to the test environment for
test. MethodsA,B,andC,useachambercapableofmaintaining40
4.4 4.4 In Method C for quasi-barrier blisters, desiccant is 6 2°C and 75 6 5 % RH. The humidification should be
placed in the blister and the lid material is sealed in place using achieved with de-ionized water, or equivalent means, to limit
equipment that is capable of correctly filling and sealing the contamination from water impurities.
D7709–11
TABLE 1 Closing Torque for Screw-type Containers
7. Reagents and Materials
Suggested Tightness Suggested Tightness
7.1 Purity of Reagents—Reagent-grade chemicals shall be
Closure
Range with Manually Range with Manually
A
Diameter, mm
used in all tests. Unless otherwise indicated, it is intended that
Applied Torque, N · m Applied Torque, in. · lbf
all reagents conform to the specifications of the Committee of
80.56 5
Analytical Reagents of the American Chemical Society where
10 0.68 6
13 0.90 8
such specifications are available. Other grades may be used,
15 0.56 – 1.02 5 – 9
provided it is first ascertained that the reagent is of sufficiently
18 0.79–1.13 7–10
high purity to permit its use without lessening the accuracy of
20 0.90–1.36 8–12
22 1.02–1.58 9–14
the determination.
24 1.13–2.03 10–18
7.2 Desiccant for Method A—During development of
28 1.36–2.37 12–21
Method A, anhydrous calcium chloride in granular form was
30 1.47–2.60 13–23
33 1.69–2.82 15–25
used as the desiccant. Other desiccants may be suitable; for
38 1.92–2.94 17–26
example, a molecular sieve or silica gel. If calcium chloride is
43 1.92–3.05 17–27
1 1
used, it shall be pre-dried at 215 65°C for 7 ⁄4 6 ⁄4)hto 48 2.15–3.39 19–30
53 2.37–3.39 21–30
ensure that any calcium hexahydrate present is fully converted
58 2.60–4.52 23–40
to the anhydrate. Cool the desiccant in a desiccator for at least
63 2.82–4.86 25–43
2 h before use. 66 2.94–5.08 26–45
A
7.3 Desiccant for Methods B and C—During development
For a closure having diameter between two diameters listed, use the torque
range for the next larger diameter.
of Method B, silica gel was used as the desiccant. It was used
in a molded form to fit the size and shape of the blister used.
Other desiccants may be suitable, for example, a molecular
9. Calibration
sieve. If silica gel is used, it shall be pre-dried in a circulating
9.1 Theweighingbalanceusedtoweighthecontainersshall
1 1
hot air oven at one of two conditions: 155 6 5°C for 3 ⁄4 6 ⁄4
be appropriately calibrated.
1 1
hor150 6 5°C for 4 ⁄4 6 ⁄4 h. Dry molecular sieve in a muffle
9.2 The environmental chamber shall be appropriately cali-
1 1
furnace at 595 6 25°C. Dry the 4Aand 3Asieves for 3 ⁄4 6 ⁄4
brated.
1 1
h. Dry the 13X sieve for 5 ⁄4 6 ⁄4 h. Cool the desiccant in a
9.3 The oven(s) used for drying desiccant shall be appro-
desiccator for at least 2 h before use.
priately calibrated.
8. Sampling, Test Specimens, and Test Units
10. Procedure
8.1 Method A (Bottles)—Use 15 bottles and 15 closures
NOTE 2—All samples should be handled in a manner that prevents
chosen to represent the package form to be tested. Reserve the
contact with skin or skin secretions and contaminants. Tweezers, forceps,
bottles for preparation at the time of testing. The bottles and
and powder-free laboratory gloves have been used successfully.
closures should be stored such that they will not be damaged;
10.1 Method A—Bottles:
particularly the mating surfaces of bottle and closure. Prepare
10.1.1 Bottles shall be received in the test laboratory, filled,
the test specimens by filling each bottle ⁄3 with desiccant then
and closed in accordance with Section 8.
close the container in the appropriate manner as quickly as
10.1.2 Mark each container with a unique identifier. Mark
possible, including any membrane seal (tamper-evident or
with indelible ink on the container. Do not use a label.
otherwise), if appropriate. Filling of bottles shall be done in a
10.1.3 Weigh each container at ambient temperature and
low-humidity atmosphere (as low as possible, but not g
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