Integration of Green Chemistry Approach for Development of Box-Behnken Design Assisted RP-HPLC Method for Estimation of Nepafenac in Ophthalmic Dosage Form: A QbD Supported Degradation Approach

Background

NSAIDs, or Non-Steroidal Anti-Inflammatory medicines, are a large family of chemically diverse medications with a wide range of effects. Nepafenac is an anti-inflammatory medication that is used topically as an aqueous solution.

Objectives

To develop a simple, dependable, and eco-friendly Reverse-Phase High-Performance Liquid Chromatographic (RP-HPLC) approach for the quantitative measurement of nepafenac in ophthalmic solutions using a Quality by Design (QbD) methodology.

Materials and Methods

A Box-Behnken experimental design was used to refine the process and identify the variables influencing chromatographic performance. Chromatographic separation was achieved on a Shimadzu C18 column (250 x 4.6 mm i.d., 5 µm) using a mobile phase of methanol:0.1% orthophosphoric acid in water (75:25 v/v), adjusted to pH 3.0, at a flow rate of 1.1 mL/min and detection at 236 nm.

Results

Nepafenac was eluted with a retention time of 4.018 min and showed great accuracy, with recovery ranging from 98.2% to 101.9%. The test for the commercial ophthalmic formulation produced a 96.16% result. Studies on forced deterioration in acidic, alkaline, oxidative, thermal, and photolytic environments validated the method’s stability-indicating properties. Furthermore, the eco-friendliness of the created method was confirmed by evaluating its environmental sustainability using AGREE and the GAPI greenness assessment method.

Conclusion

The appropriateness of the suggested method for regular quality control analysis of Nepafenac in ocular dosage forms was demonstrated through its validation in compliance with International Council for Harmonisation (ICH Q2(R2)) criteria.