Formulation Optimization of Felodipine Push–Pull Osmotic Pump Capsules Using Quality by Design Approach

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R2 based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R2 ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules.