Multivariate UV-spectrophotometric methods and Quality by Design (QbD) HPLC are described for concurrent estimation of avanafil (AV) and dapoxetine (DP) in the binary mixture and in the dosage form. Chemometric methods have been developed, including classical least-squares, principal component regression, partial least-squares, and multiway partial least-squares. Analytical figures of merit, such as sensitivity, selectivity, analytical sensitivity, LOD, and LOQ were determined. QbD consists of three steps, starting with the screening approach to determine the critical process parameter and response variables. This is followed by understanding of factors and levels, and lastly the application of a Box-Behnken design containing four critical factors that affect the method. From an Ishikawa diagram and a risk assessment tool, four main factors were selected for optimization. Design optimization, statistical calculation, and final-condition optimization of all the reactions were Carried out. Twenty-five experiments were done, and a quadratic model was used for all response variables. Desirability plot, surface plot, design space, and three-dimensional plots were calculated. In the optimized condition, HPLC separation was achieved on Phenomenex Gemini C18 column (250 × 4.6 mm, 5 μm) using acetonitrile-buffer (ammonium acetate buffer at pH 3.7 with acetic acid) as a mobile phase at flow rate of 0.7 mL/min. Quantification was done at 239 nm, and temperature was set at 20°C. The developed methods were validated and successfully applied for simultaneous determination of AV and DP in the dosage form.
Avanafil (AV) is the phosphodiesterase (PDE) type 5 inhibitor drug used in erectile dysfunction, having pyrrolidine, pyrimidine, carboxamide, and chlorine as functional groups which can easily break by environmental changes and cause toxicity. Henceforth, in detail, HPLC stability study with the Quality-by-Design (QbD) approach is presented which leads to recommended storage conditions. The stability of AV was analyzed in hydrolysis, photolysis, and thermal and oxidative conditions. The application of the QbD approach during the stability method development comprises steps as screening and optimization. Quality target product profile (QTPP) was defined, and critical quality attributes (CQAs) were assigned to meet the QTPP requirements. Primary parameters obtained from the Ishikawa diagram were studied via Placket–Burman, and four critical factors were optimized through the central composite design (CCD). The finalized method includes mobile phase [10 mM ammonium acetate, pH 4.5 adjusted by acetic acid:ACN (60:40, v/v)] at 0.9-mL/min flow rate and 239-nm wavelength. A control strategy was set up to ensure that the method repeatedly meets the acceptance criteria. Overall, 16 degradation product peaks of AV in all conditions (solid and solution state) were identified with optimized method and evaluated by HPLC-PDA study. A comprehensive systemic optimization of AV stability study is stated for the first time, which reveals that AV is prone to degrade in sunlight, moisture, and temperature. Global regulators and manufacturers should take care of the packaging, handling, and labeling of AV. A fully validated LC–MS compatible stability method can be successfully applied to monitor AV stability from its formulation which can be wisely extrapolated to assess the AV from biological samples.
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