QbD-Based Development, Greenness and Blueness Evaluation of a Stability-Indicating HPTLC Method for Ivacaftor with Mass Spectrometric Identification of Degradation Products

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Aim/Background: Quality by Design (QbD) is a structured approach to pharmaceutical development that emphasizes a deep understanding of processes and control of variability to ensure consistent quality. This study aims to develop and validate a robust, eco-friendly HPTLC-based analytical method for the quantification of Ivacaftor in bulk drug and pharmaceutical formulations, in alignment with QbD principles. Materials and Methods: The method development incorporated QbD tools such as risk assessment, method optimization, and robustness testing. HPTLC analysis was performed on silica gel pre-coated plates using a mobile phase composed of toluene, ethyl acetate, and methanol (6:2:2 v/v/v). Detection was carried out at 312 nm using UV spectroscopy. The method was validated as per ICH guidelines for specificity, linearity, accuracy, precision, and robustness. Forced degradation studies were conducted under various stress conditions (acidic, alkaline, oxidative, thermal, photolytic, and neutral), and degradation products were identified using Mass Spectrometry (MS). The method’s environmental sustainability was assessed using AGREE, GAPI, and BAGI tools. Results: The developed HPTLC method demonstrated excellent linearity with a correlation coefficient (r²) of 0.9995. The recovery values ranged from 99.71% to 100.22%, indicating high accuracy. The method also exhibited good specificity, precision, and robustness. Stress degradation studies revealed distinct degradation products, which were successfully identified through MS, providing valuable insights into Ivacaftor’s stability profile. AGREE, GAPI, and BAGI assessments confirmed the method’s greenness and eco-friendliness. Conclusion: The proposed HPTLC method, developed under QbD principles and validated as per ICH guidelines, is accurate, robust, and suitable for routine analysis of Ivacaftor. The incorporation of degradation product identification and green analytical metrics enhances its applicability for stability studies and quality control in pharmaceutical settings.

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