Eco-friendly green HPLC-ELSD and HPLC-UV methods for estimation of hydroxypropyl cellulose, aspartame, and cherry flavor in Montelukast sodium chewable tablets: A reverse engineering approach

In this study, a reverse engineering approach is utilized to evaluate and estimate critical excipients in Reference Listed Drug Products (RLDs), aiding in the formulation of cost-effective generics drug products. The key excipients, Hydroxypropyl cellulose (HPC), aspartame, and cherry flavor, used in the manufacturing of Montelukast sodium chewable tablets (for asthma and allergic rhinitis treatment), were quantitatively estimated using newly developed HPLC-UV and HPLC-ELSD methods. HPLC-ELSD separation for HPC was achieved in 35-minutes using a binary gradient consisting of water-formic acid-acetonitrile with a C₁₈ column (150x4.6-mm,4.6-µm), flow rate of 0.4-mL/min, injection volume of 50-µL, column temperature of 35 °C, and evaporator temperature of 85 °C. Aspartame and cherry flavor were estimated using HPLC-UV method consisting of 30-minutes gradient with phosphate buffer-acetonitrile along with a C₁₈ column, flow rate of 0.8-mL/min, injection volume of 50-µL, column temperature of 35 °C, auto-sampler of 10 °C, and UV detection at 220-nm for aspartame and 248-nm for cherry flavor. Method validation studies performed as in-line with the USP<1225> and ICH, Q2(R2) guidelines, demonstrating excellent specificity (no peak overlap and interference), precision, recovery (90.0–110.0 %), and linearity (HPC: 93.839–387.989 µg/mL with R² > 0.9980; Aspartame: 5.05–119.23 µg/mL with R² > 0.9998; Cherry flavor; 5.04–121.03 µg/mL with R² > 0.9999). The validated HPLC-ELSD and HPLC-UV methods were supported real-time quantitative analysis of excipients in Montelukast sodium tablets, aiding in the reverse engineering process for the generic drug products development. These methods and approach can also be utilized for the RLDs where HPC, aspartame and cherry flavor are critical role in generics product development (ANDAs).