How to Test Blister Cards by USP <661.2>: The CS Analytical Approach

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Testing blister cards according to USP <661.2> requires careful preparation because blister configurations vary in cavity size, shape, lidding material, and sealing requirements. At CS Analytical, this process includes drawing interpretation, tooling creation, fill volume determination, filling and sealing, and extraction and analysis. This laboratory-scale approach allows blister cavities to be filled with USP-grade water and sealed in-house, eliminating the need for clients to prepare water-filled blister samples on their manufacturing lines. 

Step 1: How Are Blister Drawings Reviewed? 

The first step is reviewing the technical drawing and samples to confirm the blister configuration and identify the cavity or section that must be filled. 

Technical drawings provide important information about the dimensions and layout of the blister package. The laboratory uses this information to confirm that the samples received correspond to the intended configuration and to identify the appropriate test area. 

Correct interpretation at this stage is important because the blister configuration affects tooling, nominal volume, sample quantity, and subsequent sample preparation. 

Step 2: Why Is Custom Tooling Needed? 

Custom tooling allows each blister configuration to be sealed using laboratory-scale blister-sealing equipment. 

Because blister dimensions and configurations, like their contents, vary, the tooling must accommodate the particular blister being tested. After reviewing the blister configuration, CS Analytical works with a third-party tooling manufacturer to obtain a tooling suited to its specifications. Once available, the tooling enables samples to be filled and sealed using CS Analytical's in-house blister sealer, rather than requiring clients to prepare water-filled samples using their manufacturing equipment. 

Step 3: Why Is Nominal Volume Important? 

Nominal volume determines how much USP-grade water each blister cavity can hold and helps establish how many cavities are needed to produce sufficient extract for testing. Blister cavities typically hold much smaller volumes than bottles and other pharmaceutical containers and oftentimes, do not have explicit volumes established as would be the case with, say, a 4 oz or 60 mL bottle. Many cavities are therefore required to generate enough extract to complete all analyses.  

Determining volume early also helps establish whether sufficient blister material has been provided. Nominal volume may be determined before or alongside tooling creation. 

Step 4: How Are Blister Cavities Filled and Sealed? 

Before filling, the blister cavities are checked to ensure they are clean. They are then filled with USP-grade water and sealed using an in-house blister sealer. 

Clean cavities are important because the USP-grade water sealed inside them becomes the extract used for analytical testing. Sealing requires configuration-specific preparation as differences in blister cavity and lidding materials can affect the conditions needed to produce an appropriate seal. For each new configuration, sealing parameters are evaluated and adjusted as needed before samples proceed to extraction. 

This ability to prepare samples in the laboratory allows CS Analytical to accommodate different blister configurations without requiring clients to submit pre-filled blister cards, which can present challenges. Samples may be provided as pre-cut cards or webbing and sheets or rolls of lidding.  

Step 5: How Are Blister Cards Extracted and Tested? 

Prepared blister cards are extracted with USP-grade water most commonly at 50°C for 72 hours, after which the resulting solution is combined for USP <661.2> testing. 

During extraction, the water remains in contact with the applicable packaging surfaces inside the sealed cavities. After 72 hours, the extracts from the required cavities are collected and pooled as necessary to provide sufficient volume for analysis. 

The resulting blister extract is evaluated using four tests: 

These analyses evaluate different characteristics of the solution generated from the blister packaging. 

What Does the Complete Blister Testing Process Look Like? 

The CS Analytical approach can be summarized in five stages: 

Why does blister testing require careful planning? 

Cavity volume, tooling requirements, sample quantity, and sealing conditions can vary among blister configurations, meaning that analysts need to be prepared for these differences. Successful USP <661.2> testing, therefore, begins well before the final analytical measurements are performed. 

Accurate drawing interpretation, appropriate tooling, nominal volume determination, clean sample preparation, effective sealing, and controlled extraction all contribute to a successful study. For example, a small nominal cavity volume may increase the number of cavities needed to generate sufficient extract, while a new blister configuration may require new tooling and evaluation of sealing conditions before extraction can begin, increasing the time a study takes to complete. By filling and sealing blister cards in-house, CS Analytical provides a practical approach to USP <661.2> testing while reducing the need for clients to prepare specialized water-filled blister samples themselves. 

Addressing these factors early helps ensure sufficient material is available and supports an efficient testing process from initial sample preparation through final analysis. 

Frequently Asked Questions About USP <661.2> Blister Testing 

Do blister cards need to arrive already filled and sealed? 

No. CS Analytical can fill the appropriate cavities with USP-grade water and seal them using an in-house blister sealer and configuration-specific tooling. Cavities can be provided as cut cards or as webbing. Lidding material can be provided in sheets or on a roll. 

How much blister material is required? 

The quantity depends partly on the nominal volume of the individual cavities. A total of 120 mL of extract is required for USP <661.2> testing. 

What extraction conditions are used? 

Blister cards are most commonly extracted with USP-grade water at 50°C for 72 hours. Higher temperatures allowable by the chapter may cause melting / deterioration of common blister materials under test. 

What tests are performed on the blister extract? 

The extract is evaluated for appearance of solution (color), appearance of solution (clarity), absorbance, and total organic carbon (TOC).