Analytical Quality by Design Assisted Optimization of RP-HPLC Method for the Estimation of Palovarotene Drug Substance and Drug Product by Box–Behnken Design

Chandrasekar Raju^1*, Sivagami Bojan², Chandramouli Chinthaginjala², Meena Dravidamani², Aruna Kumari Dommaraju³and Kumanan Raghunathan⁴

¹Faculty of Pharmacy, Department of Pharmacognosy, Seven Hills College of Pharmacy, Tirupati, Andhra Pradesh, India.

² Faculty of Pharmacy, Department of Pharmaceutical Analysis, Seven Hills College of Pharmacy, Tirupati, Andhra Pradesh, India.

³Faculty of Pharmacy, Department of Pharmaceutics, Seven Hills College of Pharmacy, Tirupati, Andhra Pradesh, India.

⁴Faculty of Pharmacy, Department of Pharmacognosy, Devaki Amma Memorial College of Pharmacy, Malappuram, Kerala, India.

Corresponding Author E-mail:chandru@shcptirupati.edu.in

ABSTRACT: A QbD approach, with its emphasis on risk assessment and management, may result in the establishment of a more robust or rugged system. Critical quality attributes (CQAs) and the analytical target profile were evaluated by closely examining the detailed process for analytical QbD-based optimization parameters. RP- HPLC is considered more useful than normal phase HPLC method since it is more versatile in separating a wider range of compounds, due to its non-polar stationary phase and polar mobile phase, allowing for better control over Rt and mobile phase composition, with improved reproducibility and accuracy compared to normal phase HPLC. The current study outlines the invention and validation of the straightforward, quick, sensitive, and affordable RP-HPLC approach for investigating palovarotene in tablet formulations. Three essential elements of the RP-HPLC approach buffer pH, flow rate and ratio of MP were used in the Box-Behnken design factor screening investigations. The DOE trial version 12.0 was used to optimize the chromatographic settings. With water Platisil C18-EP (4.6 x 250 mm, 5µm) column and comprising of a mobile phase KH₂PO₄ (pH 3.5): ACN (50:50 ml) v/v, a 1.0 ml/min flow rate and UV range at 261 nm, the best chromatographic separation was accomplished. The interrelationships between MP, pH, and flow rate at 3 distinct levels are described by the Box–Behnken experimental design. RSM plots and statistical data were used to evaluate the retention duration and theoretical plate responses. The current RP-HPLC method for palovarotene was in compliance with the suggested ICH recommendations. The technique can also be utilized for quality control and laboratories evaluation aimed at the assessment of Palovarotene in the drug material and capsule formulation.

KEYWORDS: Analytical Quality by Design; Box Behnken Design; Fibrodysplasia Ossificans Progressive; Factors and Responses; Palovarotene

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