USP-Compliant Online Dissolution Testing of Antipyretic Analgesic: Automatic Addition of Internal Standard

Significance of the Topic

The measurement of drug dissolution profiles is a cornerstone in pharmaceutical development and quality control. Automated online dissolution testing enhances reproducibility, reduces human error, and accelerates throughput, ensuring compliance with pharmacopeial standards while freeing skilled analysts from routine tasks.

Study Objectives and Overview

This work demonstrates a USP-compliant online dissolution test of a combined antipyretic-analgesic tablet containing acetaminophen, acetylsalicylic acid, and caffeine. Key aims were to integrate automatic sampling, dilution, and internal standard (ISTD) addition using the Shimadzu Nexera FV HPLC platform and to compare overall workflow efficiency against conventional manual processes.

Methodology and Instrumentation

The online system employed the Nexera FV in fraction analysis mode coupled with DT-Solution software for method control and report generation. A Shimadzu SIL-30ACFV autosampler executed sample preparation, including:

• Fraction collection of dissolution medium at defined time points
• Automated suction of fraction and ISTD solution (benzoic acid in methanol)
• Mixing, dilution, and injection into the HPLC

Instruments and conditions:

• Dissolution tester: NTR-6600AST, paddle method, 900 mL pure water, 100 rpm, 37 °C
• HPLC column: Shim-pack Scepter C18-120, 100 × 4.6 mm, 5 µm
• Mobile phase: methanol/glacial acetic acid/water = 28/3/69
• Flow rate: 2 mL/min; column temperature: 45 °C; detection at 275 nm

Main Results and Discussion

System suitability tests (n=6) met USP43-NF38 criteria for resolution, tailing factor, retention time precision, and area reproducibility for all analytes and the ISTD. Online testing reduced total process time by approximately 25 % (from 6.0 h to 4.5 h). Dissolution rates at 60 min exceeded 75 % for all compounds across six vessels, satisfying pharmacopeial requirements.

Benefits and Practical Applications

• Significant labor and time savings through full automation of sampling, dilution, and ISTD addition
• Enhanced reproducibility and elimination of manual errors
• Simultaneous report generation with multi-data integration via LabSolutions DB/CS
• Scalable solution for routine QC, formulation development, and bioequivalence studies

Future Trends and Potential Uses

Advancements may include integration with laboratory information management systems (LIMS), real-time data analytics, and AI-driven predictive dissolution modeling. Miniaturization and use of green solvents could further streamline workflows and reduce environmental impact. Expansion to more complex formulations and immediate release profiling in biorelevant media are anticipated.

Conclusion

The Shimadzu Nexera FV system enabled a USP-compliant online dissolution test of a multi-component analgesic tablet with high efficiency and accuracy. Automation of ISTD addition and sample handling reduced process time by 25 % and delivered robust, reproducible results, illustrating a practical path to modernize dissolution laboratories.

Reference

USP43-NF38-49 “Acetaminophen, Aspirin, and Caffeine Tablets Dissolution”