title: Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating method for furosemide.
abstract: 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 2(n) 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.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062 Punjab, India.
authors.forename: Moolchand
authors.initials: M
authors.lastname: Kurmi
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062 Punjab, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, 160062 Punjab, India. Electronic address: ssingh@niper.ac.in.
authors.forename: Saranjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005665:Furosemide / Q000032:analysis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D010084:Oxidation-Reduction; D013997:Time Factors
chemical_list: D005665:Furosemide
keywords: Degradation products; Design of experiment; Furosemide; Stability-indicating method