Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating method for furosemide

• A systematic study involving DoE for forced degradation studies and also for the development of SIM for furosemide.
• Successful application of DoE in optimization of forced degradation conditions leading to 20–30% drug degradation.
• Enrichment of selected degradation products through DoE approach.
• Optimization of a method that resulted in acceptable resolution (Rs > 1.5) among drug and its twelve degradation products.

The study involved optimization of forced degradation conditions and development of a stability-indicating method (SIM) for furosemide employing the design of experiment (DoE) concept. The optimization of forced degradation conditions, especially hydrolytic and oxidative, was done by application of 2n full factorial designs, which helped to obtain the targeted 20–30% drug degradation and also enriched levels of degradation products (DPs). For the selective separation of the drug and its DPs for the development of SIM, DoE was applied in three different stages, i.e., primary parameter selection, secondary parameter screening and method optimization. For these three, IV-optimal, Taguchi orthogonal array and face-centred central composite designs were employed, respectively. The organic modifier, buffer pH, gradient time and initial hold time were selected as primary parameters. Initial and final organic modifier percentage, and flow rate came out as critical parameters during secondary parameter screening, which were further evaluated during method optimization. Based on DoE results, an optimized method was obtained wherein a total of twelve DPs were separated successfully. The study also exposed the degradation behaviour of the drug in different forced degradation conditions.

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