Dronedarone HCl-Quercetin Co-Amorphous System: Characterization and RP-HPLC Method Development for Simultaneous...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Dronedarone HCl (DRN), an anti-arrhythmic drug for atrial fibrillation, exhibits poor solubility (2 µg/mL) and bioavailability (4%).
• Co-amorphous systems with quercetin (QCT) are utilized to enhance DRN solubility.
• A validated, sensitive, accurate, and economical method for simultaneous DRN and QCT quantification in formulations is lacking.

Purpose of the Study:

• To develop and validate a Reverse Phase-High-Performance Liquid Chromatography (RP-HPLC) method.
• To enable simultaneous estimation of Dronedarone HCl (DRN) and quercetin (QCT) within a DRN-QCT co-amorphous system.

Main Methods:

• A DRN-QCT co-amorphous system was prepared using a 1:1 molar ratio via solvent evaporation.
• Separation was achieved using a Purospher® STAR C18 column (250 mm × 4.6 mm × 5 µm id).
• The mobile phase consisted of acetonitrile and 25 mM phosphate buffer (pH 3.6) in a 60:40 (v/v) ratio.

Main Results:

• Dronedarone HCl (DRN) and quercetin (QCT) were retained at 6.7 and 3.5 minutes, respectively.
• The method demonstrated wide linearity from 0.2 to 500 µg/mL for both analytes.
• Achieved low limits of detection (LOD) for DRN (0.0013 µg/mL) and QCT (0.0026 µg/mL), and quantification (LOQ) for DRN (0.0041 µg/mL) and QCT (0.0078 µg/mL).

Conclusions:

• The developed RP-HPLC method was validated according to ICH guidelines for linearity, precision, accuracy, and robustness.
• The method successfully quantified DRN and QCT in co-amorphous samples, including content uniformity and solubility analyses.
• The method's sensitivity and wide linearity range ensure robust and precise quantification for pharmaceutical analysis.