Comprehensive stability-indicating method development of Avanafil Phosphodiesterase type 5 inhibitor using advanced Quality-by-Design approach

Abstract

Abstract 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. Graphical abstract

Keywords

• Avanafil (AV)
• Degradation products
• Storage condition
• Quality by Design (QbD)
• Chemical stability
• Erectile dysfunction