Development and Validation of QBD-Assisted Using Central Composite Design RP-HPLC Method for Lobeglitazone Sulfate and Glimipiride in Bulk and Its Combined Dosage Form

Abstract

The simultaneous quantification bulk active pharmaceutical components and combined dosage forms is vital for ensuring quality control and therapeutic efficacy. This study addresses the need for a reliable analytical method for the simultaneous quantification of lobeglitazone sulphate (LBZ) and glimepiride (GPR), two drugs often used in the administration of type 2 diabetes. A review of existing literature reveals the absence of a quality by design (QbD)-assisted reverse phase high-performance liquid chromatography (RP-HPLC) method for this specific combination. Using a QbD approach, a robust RP-HPLC method was developed and optimized employing a central composite design (CCD). The Agilent Infinity 1270 Series HPLC system, equipped with a Zorbax SB 618 column (5 μm, 46 × 150 mm), was used. Method parameters were fine-tuned to achieve optimal resolution (7.6), tailing (1.8), and retention times of 5.6 min for LBZ and 8.6 min for GPR. The optimized mobile phase consisted of ACN:KH₂PO₄ buffer (pH 3.5, 50:50 v/v), a flow rate of 1 mL/min, and a detection wavelength of 227 nm. The developed method was validated as per current regulatory guidelines, demonstrating precision, accuracy, and sensitivity. These results underscore the effectiveness of a QbD framework in method development, ensuring reproducibility and robustness. This study highlights the broader potential of QbD-assisted analytical techniques in pharmaceutical research, paving the way for more efficient drug quality assessments and improved therapeutic outcomes across diverse drug combinations.

Graphical Abstract