Stability indicating HPLC method development and validation of Fostemsavir in bulk and marketed formulations by implementing QbD approach

Abstract

Background: Achieving a predictable degree of quality with intended and planned specifications is known as "quality by design." QbD (Quality-by-Design) is an alternative to conventional method development that places more attention on identifying and mitigating potential risks. Component of the Quality-by-Design methodology involves conducting a series of experiments to learn how various factors, including the dependant variables, affect the answers of interest. Here, we use a QbD (Quality-by-Design) loom to detail the creation and verification of a stability-indicating high-performance liquid chromatography (HPLC) method for Fostemsavir in both bulk and finished-goods forms.
 Results:
 In this work, we present a workable experimental design for optimising the RP-HPLC separation technique by identifying the optimum mobile phase concentration and flow rate. Below are the ideal chromatographic conditions as calculated by Design Expert version 13.0: Mobile phase: 80 parts acetonitrile to 20 parts formic acid (v/v), flow rate: 0.8 millilitres per minute, retention time: 3.24 minutes, column dimensions: GIST C18 (250 mm × 4.6 mm × 5.0 μm).
 Here we propose a practical experimental layout for determining the optimal mobile phase concentration and flow rate for the RP-HPLC separation technique. Using Design Expert version 13.0, the optimum chromatographic conditions were determined to be as follows: Shim-pack GIST C18 (250 mm 4.6 mm, 5.0 μ), mobile phase acetonitrile to 1% formic acid (80:20, v/v), flow rate 0.8 ml/min, and retention period 3.24 min.
 At a detection wavelength of 266 nm, it was discovered that the devised technique was linear over a concentration range of 50-90 μg/ml (r2 = 0.997). Test parameters for the system's appropriateness were determined to be 1.124 for the tailing factor and 9480 for the theoretical plates. Intraday RSD was found to range from 0.70 to 0.94, whereas interday RSD was found to range from 0.55 to 0.95 percent. Values for robustness were under 2%. The solution stability % RSD was calculated to be 0.83. The result of the assay was 100.05 percent. The created methodologies were used to studies of forced degradation, and the stressed materials were analysed. The parameters used to validate the procedure fell within the acceptable range recommended by ICH.
 Conclusion: Using Design Expert 13.0, we created a central composite design experiment that illustrates the relationships between mobile phase and flow rate across three levels, with retention duration, tailing factor, as well as theoretical plates as the responses of interest. By this work, we gain insight into the variables that affect chromatographic separation and strengthen our conviction that the HPLC method we've devised will serve our needs. Quantitative method development was applied to improve comprehension of multi-tiered method variables.