Analytical QbD Based Stability- indicating RP-HPLC method development and validation for Simultaneous estimation of Sacubitril and Valsartan in Sacubitril and Valsartan Microsphere Dosage form
Keywords:
RP-HPLC, stability-indicating, Sacubitril, Microsphere, Forced degradation study, QbD, central composite design, and quadratic modelAbstract
Quality by design means to achieve certain expected quality with the predetermined and the desired specifications.
This study aimed to develop an accurate, rugged stability indicating HPLC method for simultaneous estimation of sacubitril and valsartan in sacubitril and valsartan microsphere formulation by using QbD.
This study is done by following Design expert software, Study type response surface, and design type central composite, design model quadratic with a total run of 20.
Based on design expert, the suggested method operable design region (MODR) is selected with chromatographic conditions as mobile phase pH 6.2, 10 mM KH2PO4 as a buffer, and Acetonitrile in the ratio of 70: 30% V/V, flow rate 1.0 ml/min and column temperature 30°C using analytical column Kromasil C18 (150 mm X 4.6 mm, 5 µ) at 254 nm of detector wavelength. This method was validated as per ICH Q2 (R1) guidelines. The following parameters were considered for analytical method validation System suitability, Specificity (Blank, Placebo Interference, Forced degradation), Linearity, Precision (System precision, Method precision, Intermediate precision), Accuracy, Range, solution stability, and Robustness.
Forced degradation studies were performed on samples using acid (0.5 N hydrochloric acid), base (0.5 N sodium hydroxide), oxidation (5% v/v hydrogen peroxide), heat (60 °C), UV light (Exposed up to 1.2 million lux hours and 200 WH/m2)
Degradation of the drug product was observed in acid, base hydrolysis, Thermal, and Peroxide. The assay for the stressed samples was conducted using the developed LC method. The mass balance was found to be close to 95 to 105%, thereby proving its stability indicating power.
Validation acceptance criteria were met in all cases. This method was used successfully for the estimation of Sacubitril and Valsartan in the Sacubitril and Valsartan Microsphere Dosage form.
