Understanding the permeation testing requirements of the USP <671> Container Performance Testing chapter can be a challenge. Over the past 7-10 years there have been multiple revisions to the test methods and in some cases the actual method numbers have been changed only adding to the confusion. When determining the specific USP <671> permeation testing that your container and closure system is required to have, must start with an understanding of the various options outlined by the USP. This Part One “Blog” was drafted to provide an explanation of the permeation methods that are classified as “MVTR” methods (moisture vapor transmission rate). Utilizing these methods will provide data that equate to an actual rate of moisture permeation specific to your package system. There are eight (8) total permeation methods of which four (4) of them report results as MVTR. All methods listed are current and applicable per the December 1, 2020 USP revision. In part two of this document, we will review the four other methods that use the “Meets/ Does Not Meet” specification Method.
USP <671> Permeation Methods that Report MVTR (actual rate of permeation)
Method One (report results as MVTR)
Method 1, also called barrier protection, is applicable to multiple unit solid oral dosage form (SODF) plastic container (bottles) and closures with or without induction seals. Test sample size equals 15 containers and closures. Typically, testing is performed according to anticipated conditions of manufacture: if an induction seal is intended as part of the package system, it will be applied, and closures are torqued to assigned USP value based upon closure inner diameters or according to the final assembly specification. However, other study configurations may be performed to evaluate conditions of storage and use, such as broached seals or variable torque conditions. Desiccant used is anhydrous calcium chloride in granular form. Standard total test time is 35 days in storage at 40oC / 75% RH with standard 7 day weighing intervals at day 0, 7, 14, 21, 28, 35. MVTR Results are reported in average mg/day/container and must include the standard deviation of the 15 samples.
Method Two (report results as MVTR)
This method is similar to Method 1 and also referred to as barrier protection but is applicable to solid oral dosage form (SODF) single unit or unit-dose blister cards that are constructed of high barrier or ultra-high barrier materials. Sample size is 10 Test Units, with a test unit being defined as a minimum of 10 cavities. However, some test configurations benefit from additional cavities in a test unit, especially ultra-high barrier packaging such as foil-foil blisters, where up to 30 cavities may be included in a single test unit. Sorting out the actual required number of blister cards to be used is dependent on the total number of cavities per card and anticipated moisture transmission. As such, each configuration should be considered on an independent basis. USP Reference Standard Desiccants (molecular sieves of different sizes to fit different cavities) are sealed into each cavity of a blister card. Standard total test time is 35 days in storage at 40oC / 75% RH with standard weighing times at day 0, 7, 14, 21, 28, 35, though both weighing intervals and total test times may be modified to improve test sensitivity, especially in the case of ultra-high barrier packaging. The time between the first two timepoints, typically day 0 to day 7, is defined as the equilibrium period. MVTR Results are reported in average mg/day/cavity and must include the standard deviation of the 10 samples (test units).
Method Three (report results as MVTR)
This method is similar to Methods 1 and 2 but is applicable to solid oral dosage form (SODF) single unit or unit-dose blister cards that are constructed of low barrier materials, which quickly allow for desiccants to become saturated at test temperature and humidity conditions. Sample size is 10 Test Units with a test unit being defined as a minimum of 10 cavities. Sorting out the actual required number of blister cards to be used is dependent on the total number of cavities per card and should be considered on an individual basis. USP Reference Standard Desiccants (molecular sieves of different sizes to fit different cavities) are sealed into each cavity of a blister card. Total test time is 2 days (48 hours) in storage at 40oC / 75% RH with weigh times at day 0 and day 2. Longer test durations are likely to result in desiccant saturation, ultimately yielding meaningless results. Additional weighings within this shortened period are more likely to create variation than valuable data. MVTR Results are reported in average mg/day/cavity and must include the standard deviation of the 10 samples (test units).
Method Four (report results as MVTR)
Method 4 is applicable to solid oral dosage form (SODF) single unit or unit-dose blister cards that are constructed of low barrier, high barrier or ultra-high barrier materials, but relies on measuring the rate of moisture egress from water filled samples, as opposed to ingress to desiccant filled samples in Methods 1-3. Sample size is 10 Test Units with a test unit being defined as a minimum of 10 cavities. However, some test configurations benefit from additional cavities in a test unit, especially ultra-high barrier packaging such as foil-foil blisters, where up to 30 cavities may be included in a single unit. Sorting out the actual required number of blister cards to be used is dependent on the total number of cavities per card. In place of desiccant, water is used to fill the blister cavities prior to sealing. All weights must be taken with samples in a glove box that must maintain 25% RH. Standard total test time is 35 days in storage at 40oC / 25% RH with weigh times at day 0, 7, 14, 21, 28, 35, though both weighing intervals and total test times may be modified to improve test sensitivity, especially in the case of ultra-high barrier packaging. Because performance will not degrade the way desiccant becomes saturated, low-barrier containers can be properly measured over time assuming sufficient water is present in the cavity at test start. MVTR Results are reported in average mg/day/cavity and must include the standard deviation of the 10 samples (test units).