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

Background: Dronedarone HCl (DRN) is an anti-arrhythmic drug indicated for atrial fibrillation. DRN has a low solubility of 2 µg/mL and 4% bioavailability, thus it is formulated as a co-amorphous system to enhance its solubility by using quercetin (QCT) as a co-former. A sensitive, accurate, and economic method for the simultaneous quantification of DRN and QCT in formulation is not found in the literature.

Objective: To develop a Reverse Phase -HPLC method for the simultaneous estimation of DRN and QCT in a DRN-QCT co-amorphous system.

Method: The co-amorphous system was prepared using a solvent evaporation technique with DRN and QCT in a 1:1 molar ratio. The separation was achieved on a Purospher® STAR C18 (250 mm × 4.6 mm × 5 μm id (internal diameter)) column with the mobile phase comprising of acetonitrile and a 25 mM phosphate buffer pH 3.6 (60:40%, v/v).

Results: DRN and QCT were retained on the column for 6.7 and 3.5 min, respectively. For both molecules, the method was developed with a wide linearity range of 0.2-500 µg/mL. The LOD for DRN was found to be 0.0013 µg/mL and for QCT it was found to be 0.0026 µg/mL. The LOQ for DRN was found to be 0.0041 µg/mL, and for QCT it was 0.0078 µg/mL.

Conclusions: The method was validated as per International Conference on Harmonization (ICH) guidelines for linearity, precision, accuracy, and robustness. The method was used in simultaneous quantification of DRN and QCT in co-amorphous samples.

Highlights: The method developed was used for the analysis of content uniformity and solubility samples of co-amorphous system, where the method was able to successfully quantify DRN and QCT. Low detection and quantification limits contribute to the sensitivity of the method and wide linearity range assures the robust and precise quantification of molecules.