Response Surface Methodology Driven Systematic Development of a Stability- indicating RP-UPLC Method for the Quantification of Aliskiren: A Renin Inhibitor
Bikash Ranjan Jena
KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur-522502, Andhra Pradesh, India.
G. S. N. Koteswara Rao *
KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur-522502, Andhra Pradesh, India.
Rajasekhar Reddy Alavala
KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur-522502, Andhra Pradesh, India.
Prasanna Kumar Desu
KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur-522502, Andhra Pradesh, India.
G. Chakravarthi
KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur-522502, Andhra Pradesh, India.
Suryakanta Swain
Department of Pharmacy, School of Health Sciences, The Assam Kaziranga University, Koraikhowa, NH-37, Jorhat-785 006, Assam, India.
Debi Prasad Pradhan
Research and Development Center, Endo Pharmaceuticals Inc, Indore- 453001, Madhya Pradesh, India.
P. Niharika
Department of Pharmaceutical Chemistry, SIMS College of Pharmacy, Mangaldas Nagar, Guntur-522001, India.
*Author to whom correspondence should be addressed.
Abstract
Aims: The current study envisages experimental design enabled rapid, sensitive, and stability-indicating RP-UPLC method to quantify Aliskiren in its pharmaceutical formulations.
Study Design: Box-Benkhen experimental Design using Response surface methodology.
Place and Duration of Study: Department of Analytical Research and Development, Brawn laboratories ltd., Gurugram, India, and Department of Pharmacy KL College Pharmacy, KL Deemed to be University, Vaddesearam, Guntur, Andhra Pradesh, between May 2021 and September 2021.
Methodology: The chromatographic partitioning was achieved on a Waters Acuity H class UPLC system, with BEH 130οA, C18 column (100 x 2.1 mm,1.7 μm) having isocratic elution containing (50:50 %v/v) of 0.2% Glacial acetic acid (GAA) : acetonitrile, at constant flow rate using PDA detection. The optimum conditions were delineated, selecting three influential factors (CMPs), i.e., mobile phase composition, flow rate, and injection volume. Systematic optimization was accomplished by 32 Box-Benkhen design using response surface methodology (RSM).
Results: The selected variables are evaluated for obtained responses (CAAs), i.e., peak area, retention time (Rt), USP Plate count. The final optimized method employed, organic phase composition 0.2 % GAA (pH 3.0) and acetonitrile 50:50 (% v/v) with 0.3 mL min-1 flow rate. The injection volume was maintained as 2μL with 2 minutes run time and λmax 280 nm.
Conclusion: The method was linear for 5-300 ppm, with regression co-efficient (R2) 0.9995. As per ICH guidelines, forced degradation studies were carried out to analyse the stability profile of drug. The short Rt 1.214, minute implies superior robustness, sensitivity, and cost-effectiveness for routine analysis. The results exhibited that RSM approach of QbD will be competently used to optimize the RP-UPLC method with fewer experimental trials and error-free investigation.
Keywords: Chromatography, stability, specificity, renin-inhibitor, Design of experiment, Validation