Shimadzu Nexera FV - Ultra High Performance Liquid Chromatograph for Online Dissolution Testing

Significance of the Topic

The integration of online ultra high performance liquid chromatography (UHPLC) into pharmaceutical manufacturing enables real-time monitoring of chemical synthesis and dissolution processes. This approach supports Quality by Design (QbD) principles and Process Analytical Technology (PAT), ensuring consistent product quality and reducing human error and labor intensity.

Objectives and Study Overview

This document describes the development and capabilities of the Nexera FV UHPLC system coupled with LabSolutions FV software. The main goals are:

• Automate sample collection, analysis, and reporting in flow and batch reaction monitoring.
• Streamline dissolution testing with minimal operator intervention.
• Maximize system utilization by enabling both online and standalone UHPLC operation.

Methodology and Instrumentation

The system comprises:

• Nexera FV UHPLC with flow-through vial autosampler.
• LabSolutions FV software for automated scheduling and data processing.
• Flow synthesis and batch synthesis reactors or dissolution testers connected via sampling valves.

Two analytical modes are available:

• Direct Injection Mode for reactions or dissolution samples where analysis completes before the next sampling.
• Fraction Mode supporting high-frequency sampling (as fast as every 5 minutes) with automatic fractionation and dilution capabilities.

Key pretreatment functions:

• Online sample dilution with accuracy within ±10% across dilution ranges.
• Automated addition and mixing of internal standards with high repeatability (<0.3% RSD).

Main Results and Discussion

The integrated Nexera FV system demonstrated:

• Reliable real-time monitoring of flow synthesis, batch reactions, and dissolution testing, eliminating manual sampling errors.
• High sample throughput and data reliability through automatic dilution and internal standard addition.
• Efficient software-driven scheduling that exploits instrument idle times for data processing, saving over an hour in extended protocols.
• Long-lasting consumables enabling continuous operation (vial septa lasting up to 200 injections without leakage).

Benefits and Practical Applications

• Significant labor savings by automating sampling, analysis, and reporting tasks.
• Enhanced data accuracy and consistency supporting PAT and regulatory compliance.
• Flexibility to switch between online monitoring and conventional UHPLC analyses to maximize instrument utilization.
• Reduced risk and cost in batch reaction monitoring via automatic sample dilution and precise timing.

Future Trends and Potential Applications

• Integration with advanced process control systems for closed-loop feedback in manufacturing.
• Expansion into other industries requiring continuous quality monitoring, such as food and chemicals.
• Adoption of machine learning for predictive analytics using high-frequency chromatographic data.
• Further miniaturization and multiplexed sampling for higher throughput and lower footprint.

Conclusion

The Nexera FV UHPLC system combined with LabSolutions FV software offers a robust, automated platform for online analysis in pharmaceutical production. By reducing manual intervention and improving data reliability, this solution aligns with modern regulatory expectations and drives efficiency across synthesis and dissolution workflows.