title: QbD-Based Development and Validation of a Stability-Indicating HPLC Method for Estimating Ketoprofen in Bulk Drug and Proniosomal Vesicular System.
abstract: The current studies entail systematic quality by design (QbD)-based development of simple, precise, cost-effective and stability-indicating high-performance liquid chromatography method for estimation of ketoprofen. Analytical target profile was defined and critical analytical attributes (CAAs) were selected. Chromatographic separation was accomplished with an isocratic, reversed-phase chromatography using C-18 column, pH 6.8, phosphate buffer-methanol (50 : 50v/v) as a mobile phase at a flow rate of 1.0 mL/min and UV detection at 258 nm. Systematic optimization of chromatographic method was performed using central composite design by evaluating theoretical plates and peak tailing as the CAAs. The method was validated as per International Conference on Harmonization guidelines with parameters such as high sensitivity, specificity of the method with linearity ranging between 0.05 and 250 µg/mL, detection limit of 0.025 µg/mL and quantification limit of 0.05 µg/mL. Precision was demonstrated using relative standard deviation of 1.21%. Stress degradation studies performed using acid, base, peroxide, thermal and photolytic methods helped in identifying the degradation products in the proniosome delivery systems. The results successfully demonstrated the utility of QbD for optimizing the chromatographic conditions for developing highly sensitive liquid chromatographic method for ketoprofen.
authors.affiliation: Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India.
authors.forename: Nand K
authors.initials: NK
authors.lastname: Yadav
authors.affiliation: Jubilant Life Sciences Limited, Noida, Uttar Pradesh 201301, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Raghuvanshi
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India Formulation Research, Ipca Laboratories Limited, Kandivli Industrial Estate Ltd., Kandivli (W), Mumbai, Maharashtra 400067, India.
authors.forename: Gajanand
authors.initials: G
authors.lastname: Sharma
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
authors.forename: Om P
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India sn_mdu@rediffmail.com.
authors.forename: Sanju
authors.initials: S
authors.lastname: Nanda
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards*; D004339:Drug Compounding; D004355:Drug Stability; D005163:Factor Analysis, Statistical; D006601:Hexoses / Q000737:chemistry; D006801:Humans; D007660:Ketoprofen / Q000032:analysis*; D054709:Lecithins / Q000737:chemistry; D057230:Limit of Detection; D008081:Liposomes / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D015203:Reproducibility of Results; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D006601:Hexoses; D054709:Lecithins; D008081:Liposomes; D013501:Surface-Active Agents; C018665:sorbitan monooleate; D019301:Oleic Acid; D007660:Ketoprofen; D002784:Cholesterol