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36 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m Lyophilization vents the generated iodine at the anode from being reduced back to iodide at the cathode. Two differ- ent reagents, an anolyte and catholyte, are required. In a fritless cell, only one reagent containing all the necessary components is used, and through the design of the cell, the iodine will not react at the cathode and be reduced back to iodide (Figure 5). In both systems, the cathode and anode are platinum electrodes, which induce a current through the cell. Both ty pes of reaction cells a r e a p pr o pr i a t e for t e s t i n g lyophilized product. The fritted cell is preferred when the sample being tested is known to interact w it h const ituents w it hin t he reagents, a nd t herefore, t wo different Karl Fischer reagents are required. Reactions with the Karl Fischer reagents are discussed in more detail in the "Points to Consider" section. The fritless cell requires only one reagent and is easier to maintain. Over the years, improvements have been made to the Karl Fisher reagents to remove pyridine, a noxious carcinogen. Currently, the reagents generally contain im- idazole or other primary amines. Sample preparation and intro- duction into the reaction cell may entail using an anhydrous solvent, such as methanol, to dissolve the dried product or extract the water when a suspension forms. An al- ternate method employs evapo- ration: The sample is heated and a dried gas such as nitrogen is used as a carrier, passing the gas over the heated sample then per- colating the carrier gas through the reagent in the reaction cell. A suitable method should be developed to yield confidence in the accuracy and precision across the range of possible moisture levels for a mate- rial. A significant amount of time and effort is often required to develop a specific water extrac- Figure 4: Fritted cell. Figure 5: Fritless cell.