A Robust, Automated Karl Fischer Titration System - Pharmaceutical Technology

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A Robust, Automated Karl Fischer Titration System
The authors developed a robust, automated system to conduct Karl Fischer moisture assays for lyophilized products.


Pharmaceutical Technology
Volume 33, Issue 11, pp. 52-60

The DL31 titrator includes a small vacuum pump for withdrawing and dispensing solvent from the titration cell. However, that setup is not sufficiently powerful to ensure the full removal of the cell contents and accurate dispensing of solvent. Hence, the automated system performs the fluid handling (e.g., waste removal and solvent dispensing) with a pair of Masterflex L/S computer-compatible peristaltic pumps that also offer RS-232 serial connectivity. The fluid-path contact surface includes PTFE and chemical-resistant Masterflex Tygon Chemical tubing.

The samples are shuttled between the various stations by a Mitsubishi RV-2AJ-511 five-axis industrial robot arm equipped with a set of custom triposition grippers. This robot has a proven track record in industrial settings, is reliable, is widely used, and also is controlled through RS-232 serial communication. Furthermore, the robot arm controller provides several digital input–output lines that can power solenoid valves, thus permitting the actuation of pneumatic cylinders for the decapping station and the titration cell cap.

AB Controls (Irvine, CA) integrated all the components and placed them aboard a compact, custom-fabricated aluminum frame. The Focus software, AB Controls's automation and robotics application, was customized to control all operations from a standard computer equipped with the Windows operating system and a multiport serial-communication card.


Figure 2: Automated Karl Fischer titration system components. Side view (a) and top view (b) of the titration deck. The footprint is approximately 95 x 110 cm. Components include the result line printer (1), UPS for entire robotic system (2), Windows XP computer (3), Mitsubishi robot controller (4), sample tube rack that includes 105 positions (5), titration-cell pneumatic sealing mechanism assembly (6), Mitsubishi robot arm (7), Mettler–Toledo XP analytical balance (8), Mettler–Toledo DL 31 volumetric Karl Fischer titrator (9), solvent-delivery and waste-removal peristaltic pumps (10) and (11), waste bottle (12), solvent bottle (13), pneumatic decapping station (14), cap holder (15), spent-sample tube chute to trash bin (16), hydranal reagent bottle and holder (17), and ionizer for static charge control (18). (IMAGE IS COURTESY OF PHILIPPE LAM)
Figure 2 shows the entire setup, including the sample rack, which holds a total of 105 samples contained in standard 15-cm3 screw-cap polypropylene centrifuge tubes. The system was designed primarily for robustness and reduces the potential for operator and hardware errors by minimizing the number and complexity of operational steps. In addition, numerous step-completion verification and safety checks are included in the run sequence. For example, before starting a run, the system verifies that the balance chamber is empty to prevent placing a sample tube in a location that is already occupied. At the decapping station, the system ensures that the cap has been removed from the sample tube before attempting to dispense the sample into the titration cell.


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