Development and validation of a QbD-integrated sensitive RP-HPLC method for quantitation of fenofibrate: an...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Fenofibrate is a lipid-regulating drug often formulated in sustained-release (SR) tablets.
• Alcohol consumption can lead to dose dumping in SR formulations, compromising safety and efficacy.
• Developing a reliable analytical method is crucial for assessing fenofibrate SR formulations, especially concerning alcohol-induced dose dumping.

Purpose of the Study:

• To develop and validate a sensitive, robust, and efficient High-Performance Liquid Chromatography (HPLC) method.
• To quantify fenofibrate in a gel-matrix SR tablet formulation.
• To assess the formulation's resistance to alcohol-induced dose dumping.

Main Methods:

• A Quality by Design (QbD) approach and Box-Behnken design were employed to optimize chromatographic variables.
• Method validation was performed according to International Council for Harmonisation (ICH) Q2 (R1) guidelines.
• Analysis utilized a Shimadzu HPLC system with a PDA detector, optimized mobile phase (acetonitrile:water, pH 2.5), C18 column, and a 40°C column temperature.

Main Results:

• The developed RP-HPLC method exhibited high sensitivity (LOD: 0.0438 µg mL⁻¹, LOQ: 0.132 µg mL⁻¹) and linearity (R² = 0.999) over the range of 5-80 µg mL⁻¹.
• The method demonstrated improved sensitivity and a significantly reduced retention time compared to previous RP-HPLC methods.
• The method was successfully applied to evaluate blend uniformity, content uniformity, assay, and dissolution of fenofibrate SR tablets under alcohol-induced dose-dumping conditions.

Conclusions:

• The developed RP-HPLC method is sensitive, robust, and efficient for fenofibrate quantification.
• This validated method is suitable for dose dumping studies of fenofibrate SR tablet formulations.
• The method ensures reliable assessment of formulation performance and patient safety.