Development of Analytical Quality by Design RP-HPLC Method and Its Validation for Estimation of Gefitinib from Bulk, Tablet Dosage Form and Complex Nanoformulation.

BACKGROUND Estimation of the drug and development of the method is a critical aspect of formulation development and a critical factor for analytical scientists. Gefitinib is a poorly soluble anticancer drug. OBJECTIVE The present research enlightens the topic of the development of innovative quality by design methods for the estimation of Gefitinib (GF) from bulk, pharmaceutical tablet formulation and complex nanoformulations. METHODS To simplify the estimation of poorly soluble drugs like GF, Response Surface Methodology (RSM) was adopted with effective leverages to obtain precise computation design space using the Box-Behnken Design (BBD) model. The major 3 mixed effect independent factors (Percentage of Buffer, pH of buffer and flow rate) were screened with 3 prominent dependent responses (viz., Theoretical Plate, Retention Time, and Tailing Factor) selected for optimal analysis. Furthermore, co-processed steps were employed for the estimation of the analyte from the complex formulation. RESULTS The RP-HPLC method utilizes the quality by design (QbD) approach can effectively estimate the analyte concentration of less than 4.5 min. The developed method was economically robust, and sensitive and shows a % relative standard deviation (%RSD) of less than 2% for all the selected validation parameters. The estimated design space suggests the highest desirability (R2-0.998) at 60% of buffer in the mobile phase, pH 4.25, and flow rate of 0.7 mL/min. CONCLUSION The QbD approach was used to design and develop the method by understanding the interaction between dependent and independent variables to get the optimum values. The developed method was validated successfully and can be useful for formulation scientists to estimate drug concentration and drug release profiles from complex nanoformulations. HIGHLIGHTS The analytical approach was designed and quantified using a quality-by-design approach to make the RP-HPLC method more robust and efficient for the estimation of analytes from complex nanoformulations. The method is also useful to eliminate the interfering molecule during estimation by employing co-processing steps. The developed method saves time, and cost of solvent and employs QbD as a requirement of recent regulatory concern.