Debashish GHOSE, Suryakanta SWAIN, Bikash Ranjan JENA, G.S.N. Koteswara RAO, Umasankar KULANDAIVELU, Rajasekhar Reddy ALAVALA, Siva Prasad PANDA, Gurudutta PATTNAIK, Debi Prasad PRADHAN

Analytical QbD based systematic development of a novel RP-UHPLC method for the quantification of Albuterol sulphate in its metered dose inhaler formulations

Albuterol sulphate is a Beta-2–adrenergic agonist drug mainly used in the form of nasal inhalations to treat chronic bronchitis and chronic obstructive pulmonary disease (COPD). A simple, rapid, precise chemometricsbased RP-UHPLC method has been developed and validated in its MDI formulations by the QbD approach. The chromatographic separation was achieved by Hibar HR purospher STAR RP-18 encapped column (C18, 250 mm × 4.6 mm, 5 μm) with UV detection λmax 225 nm. The retention time (Rt) for albuterol sulphate was observed as 2.434 over a run time of 5 minutes. Optimization of the method for the quantification of albuterol sulphate in its metered dose inhaler formulations has been performed by using 22 central composite design with response surface methodology that might lessen the solvent consumption, duration, and additional resources. A total of two independent variables, organic phase composition, and flow rate, were analyzed to construct a quadratic process model to examine the effect of independent variables or critical material attributes (CMAs) ahead the observed responses known as the critical method parameters (CMPs) within the designed space. The optimized UHPLC method contains phosphate buffer (10 mM KH2PO4) and acetonitrile (60:40 %v/v) as the mobile phase, which was delivered with a flow rate of 1.0 ml/min and the column was maintained at 40°C. The developed QbD based method was subsequently validated as per ICH Q2 R1 guidelines. The method obeyed linearity within the range of (5-120 μg/mL) with regression R2 of 0.999 for albuterol sulphate. The low coefficients of variation obtained in the intraday and inter-day precision studies indicate précised method. High recovery of albuterol sulphate has been observed within the range of (98.0-102.0 %). The developed method can be intensely employed as a highly robust, accurate, and cost-effective for routine analysis in research labs that competitively separate the drug from its excipients.

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