In this two-part series, we are providing detailed information and test method highlights to help you understand the permeation testing requirements as outlined in the USP <671> Container Performance Testing chapter. As previously noted, this can be a challenge as over the past 7-10 years there have been multiple revisions to these test methods including changes to the method numbering system and in some cases the application requirements of the individual methods. In part-one of this “Blog”, we provided an overview of the four (4) permeation methods that are classified as “MVTR” results methods (moisture vapor transmission rate). In this part-two document, we will review the four other methods that use the “Meets/ Does Not Meet” specification Method. These methods are current per the USP December 1, 2020 published revision. Ultimately, these “Meets/ Does Not Meet” methods enable a designation for a package system to be defined as either “tight” or “well-closed”. In the case of blister cards or single unit dose systems, a classification of A, B, C, or D is used.
USP <671> Permeation Methods that Report results as MEETS / DOES NOT MEET Specification
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 sample 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 sample 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.