Automating Dissolution Testing with an Agilent Online LC System

Importance of Topic

Dissolution testing is a fundamental quality-control method in pharmaceutical development and manufacturing, providing key insights into drug release rates and ensuring batch-to-batch consistency. Automating this process reduces manual intervention, minimizes human error, and delivers real-time dissolution profiles essential for rapid decision-making.

Objectives and Study Overview

This study demonstrates a fully automated dissolution testing workflow by integrating an Agilent InfinityLab Online LC system with an Agilent 1290 Infinity Flexible Cube module. The goal was to enable unattended, real-time sampling and analysis of dissolution samples from six vessels, improving accuracy and efficiency for both sustained-release and immediate-release dosage forms.

Instrumentation

• Agilent 708-DS dissolution apparatus
• Agilent InfinityLab Online LC system comprising:
  • 1260 Infinity II Flexible Pump
  • 1260 Infinity II Online Sample Manager
  • 1260 Infinity II Multicolumn Thermostat with heat exchanger
  • 1260 Infinity II Diode Array Detector (Max-Light flow cell)
• Agilent 1290 Infinity Flexible Cube (reciprocating piston pump, 12-port stream selector, quick-change valves)
• Software: Agilent OpenLab CDS v2.7 and Agilent Online LC Monitoring v1.1

Methodology

• Standard Preparation: Sodium valproate solutions (0.3 mg/mL) in HPLC-grade water.
• LC Conditions: Poroshell EC C18 3.0 × 50 mm, 2.7 μm; 45 °C; mobile phase 10 mM phosphate pH 2.0/acetonitrile (60:40); 2.0 mL/min; detection at 210 nm; 1 min run time.
• Tubing Validation: Flushing for ≥82.5 s to achieve >99.5% analyte recovery in transfer lines before each injection.
• Automated Workflow: The Flexible Cube switches sampling valves and pumps dissolution solution to the LC for direct injection at scheduled intervals. Synchronization of dissolution apparatus dosing and LC acquisition is managed by the CDS software.
• Sampling Schedules:
  • Sustained-release tablets: 1, 3, 6, 12 h intervals (minimum 5 min between vessels).
  • Immediate-release tablets: 3, 15, 30, 45 min intervals (2 min between sample points).

Main Results and Discussion

• Sustained-release tablets: Six-vessel replicate sampling at 1, 3, 6, 12 h produced RSD ≤2.4% for peak area. Mean dissolution rates: 24.1% (1 h), 45.8% (3 h), 69.0% (6 h), 82.6% (12 h).
• Immediate-release tablets: Sampling at 3, 15, 30, 45 min yielded RSD ≤1.5%. Dissolution exceeded 98% by 15 min and remained consistent thereafter.
• The automated system delivered consistent, high‐resolution dissolution profiles with reduced labor and lower risk of timing errors compared to manual sampling.

Benefits and Practical Applications

• Real-time, unattended monitoring of dissolution kinetics.
• Enhanced reproducibility and throughput in QC and formulation studies.
• Reduced operator workload and elimination of manual syringe sampling.
• Applicable to both sustained-release and immediate-release formulations, and adaptable to other kinetic assays.

Future Trends and Opportunities

• Integration with process analytical technology (PAT) for real-time release testing.
• Expansion to high-throughput dissolution screening and combinatorial formulation studies.
• Coupling with multivariate data analysis for predictive release modeling.
• Potential extension to automatic monitoring of other reaction-based assays.

Conclusion

Coupling an Agilent InfinityLab Online LC system with the Agilent 1290 Infinity Flexible Cube enables fully automated, real-time dissolution testing of pharmaceutical dosage forms. This approach improves data quality, reproducibility, and laboratory efficiency while minimizing manual intervention and human error, offering a versatile solution for drug development, quality control, and regulatory compliance.