Development and Validation of a Systematized Liquid Chromatographic Method for Estimation of Roflumilast in Tablets and in Presence of its Degradation Products

Abstract

Background: Roflumilast (ROF) is an antiasthmatic drug used frequently for treating chronic obstructive pulmonary disease (COPD). The various reported methods developed with a non-systematised traditional workframe for routine estimation of ROF in formulations indicated the demand for developing a systematised new method.  Objective: In the present study, an attempt was made to develop a new validated liquid chromatographic method with federal flexibilities and stability-indicating potential. Method: A time-efficient, rapid, and systematised quality by design (QbD) approach was developed to avail regulatory flexibilities with assured performance. Defining the analytical target profile (ATP) and associated critical analytical attributes (CAAs) helped control the method’s performance. Methanol proportion, flow rate, pH, and detection wavelength were the four identified critical method variables (CMVs) that were further studied for robustness investigation. Moreover, the control strategies for CMVs were defined as per method intent. Chromatography constituted methanol: water (pH 3.5 maintained by orthophosphoric acid) (90:10% v/v) as the mobile phase, flowing at 1.2 ml/min on a ShimPack GWS C18 column. The photodiode array (PDA) detector provided the best results at 250 nm. Results: ROF was eluted at a retention time of 3.1 min with acceptable system suitability values. Validation studies postulated method acceptability and suitability. Results for parameters viz. linearity (0.5–160 µg/ml), accuracy (> 98%), and precision (< 1%) advocated method reliability. ROF was susceptible to applied acidic and alkaline stress, requiring adequate preventive measures during formulation development. Conclusion: Overall, this method worked well for figuring out ROF even when there were product additives and possible degradation products present, showing that it can be used on a regular basis.