Understanding the permeation testing requirements of the USP <671> Container Performance Testing chapter can be a challenge. Over the past 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, you must start with an understanding of the various options outlined by the USP. This summary sheet will provide an explanation of the eight different permeation methods that our currently outlined in the USP. The first four methods are classified as “MVTR” methods (moisture vapor transmission rate). Utilizing these methods will provide data that equates to an actual rate of moisture permeation specific to your package system. Results for the first four methods are reported as MVTR and there is no assigned USP specification. Methods five through eight report the results as “Meets/ Does Not Meet” against the USP assigned specification. In the summary for each method, the key factors that determine the methods applicability to a container system are highlighted. Understanding the key components of each method will help you to more clearly define the testing needed for your package with the understanding that two methods may be completed to meet the overall objective.
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).
Method Five (report results at Meets or Does Not Meet assigned specification)
Method 5 is a required classification test for multiple unit solid oral dosage form (SODF) plastic packages; either those without an impervious (induction) seal, or those that will have an end-use and storage period with an open (broached) induction seal. Test sample size equals 17 total containers and closures with 10 bottles defined as test samples, 2 defined as controls, and 5 containers used for volume determination. Closures must be torqued shut to the assigned USP value based upon closure inner diameters, though custom torque values can be applied to reflect actual manufacturing conditions. Desiccant used is 4-8 mesh anhydrous calcium chloride. Total test time is 14 days in storage at 23°C / 75% RH with weighing timepoints at day 0 and day 14. Moisture vapor transmission results are calculated in mg/day/liter and based upon calculations, containers are reported as meeting or not meeting specifications for “tight” or “well-closed” classifications.
Method Six (report results at Meets or Does Not Meet assigned specification)
Method 6 is a required classification test for multiple unit solid oral dosage form (SODF) plastic packages with an impervious seal, such as induction seal liners. The method may also be applied to evaluate permeation specifically through the bottle as opposed to the composite system. In place of an induction seal, other impervious seals may be utilized (glass plate and wax mixture) and when an induction seal is used, the closure can be removed to improve overall test precision. Test sample size equals 17 total containers and closures with 10 bottles defined as test samples, 2 defined as controls and 5 containers used for volume determination. Desiccant used is 4-8 mesh anhydrous calcium chloride. Total test time is 14 days in storage at 23°C / 75% RH with weighing timepoints at day 0 and day 14. Moisture vapor transmission results are calculated in mg/day/liter and based upon calculations, containers are reported as meeting or not meeting specifications for “tight” or “well-closed” classifications. Specifications to meet these standards are more stringent than those found in Method 5.
Method Seven (report results based upon specific classification A, B, C, D)
Method 7 is a classification test applicable to solid oral dosage form (SODF) single unit or unit dose containers, whether low barrier, high barrier, or ultra-high barrier. The actual number of cards to be used is dependent on the number of cavities per card, but also the materials of construction and anticipated moisture vapor transmission. However, the method requires not less than 4 packs (blister cards) and least a total of 10 units (in this case, a unit is a single cavity). The desiccant used are typically molecular sieve in pellet form and sealed in each cavity of the blister card. A corresponding number of blister cards are sealed empty to act as control samples. Storage requirements are 23oC / 75% RH with weights taken every 24 hours or suitable intervals. Moisture vapor transmission results are calculated in mg/day/cavity and based upon results, the blister card is a assigned a classification of A, B, C or D according to the package’s ability to meet specifications for each class.
Method Eight (report results based upon percent of weight loss)
Method 8 is a classification test applicable to multiple unit liquid oral dosage form (LODF) containers and operates on the principle of moisture egress from water-filled packages as opposed to moisture ingress in desiccant filled packages. Test sample size equals 12 total containers and closures with 10 sample defined as test samples and 2 defined as control samples that will be filled with glass beads. Closures must be torqued shut to the assigned USP value based upon closure diameters, though custom torque values can be applied to reflect actual manufacturing conditions. Water is used to fill the containers. Total test time is 14 days in storage at 25oC / 40% RH with weighing timepoints at day 0 and day 14. Moisture vapor transmission results are expressed as a percent of weight loss. Based upon results, containers are classified as “tight” if the assigned specification is met.