On-line Dissolution Test of Loxoprofen Sodium Tablets

Significance of the Topic

The dissolution rate of oral dosage forms is a critical quality attribute in pharmaceutical development and manufacturing. Automated on-line dissolution testing minimizes manual sampling errors, accelerates data collection, and ensures compliance with pharmacopoeial standards, enhancing throughput and reproducibility in research laboratories and quality control environments.

Objectives and Study Overview

This study evaluates the Shimadzu Nexera™ FV on-line HPLC system for automated dissolution testing of loxoprofen sodium tablets. Two analysis modes—fraction analysis and direct injection—are compared to demonstrate labor savings, data quality, and cost efficiency while meeting the Japanese Pharmacopoeia (JP) 18th Edition dissolution criteria.

Methodology and Instrumentation

A dissolution tester equipped with a dedicated sampling and filtration device was interfaced directly with the Nexera FV autosampler. Key elements include:

• Fraction Analysis Mode: Sample collection into vials or microtiter plates at 5-minute intervals; options for post-test batch HPLC runs; automated dilution and internal standard addition.
• Direct Injection Mode: Continuous sample transfer from flow vials to the HPLC system without intermediate fractionation vials, reducing consumable costs.

The chromatographic conditions were optimized for high-speed analysis based on JP methods:

• Column: Shim-pack XR-ODS II (75 × 3.0 mm I.D., 2.2 µm)
• Mobile Phase: Methanol / Water / Acetic Acid / Triethylamine = 600 : 400 : 1 : 1
• Flow Rate: 0.8 mL/min; Column Temp: 40 °C; Injection Volume: 2 µL
• Detection: UV at 222 nm

Main Results and Discussion

In fraction analysis mode, six sequential injections of a 60 mg/L loxoprofen sodium standard yielded retention time and peak area RSDs below 0.1 %, demonstrating excellent reproducibility. Time-dependent dissolution profiles from six vessels showed >85 % drug release within 30 minutes, satisfying JP requirements. Direct injection mode also achieved over 100 % dissolution at the 30-minute mark, confirming data consistency without the need for fractionation vials. Streamlined workflows eliminated manual sampling steps and maintained high accuracy.

Benefits and Practical Applications

• Labor Efficiency: Automated sampling and analysis reduce man-hours between dissolution run and HPLC measurement.
• Error Reduction: Elimination of manual transfer steps lowers risk of sample handling mistakes.
• Cost Savings: Direct injection mode removes the need for fractionation vials and associated consumables.
• Regulatory Compliance: Fully traceable, reproducible data aligned with JP and USP dissolution specifications.

Future Trends and Potential Applications

Integration of on-line dissolution systems with process analytical technology (PAT) platforms and machine-learning algorithms can enable real-time monitoring and predictive modeling of drug release. Miniaturized flow-through designs and multi-analyte capability will expand applications to complex formulations, biosimilars, and continuous manufacturing environments.

Conclusion

The Shimadzu Nexera FV on-line HPLC dissolution system effectively automates loxoprofen sodium tablet testing with high-speed, reproducible results. Both fraction analysis and direct injection modes meet pharmacopoeial dissolution criteria while offering distinct advantages in flexibility, throughput, and cost reduction, demonstrating its suitability for modern pharmaceutical quality control.

References

• Japanese Pharmacopoeia, 18th Edition.
• Shimadzu Corporation. Nexera™ FV Application Note, First Edition: Dec. 2023.