Assessment of Fractional Factorial Design for the Selection and Screening of Appropriate Components of a Self-nanoemulsifying Drug Delivery System Formulation

Purpose: Recently, a self-nanoemulsifying drug delivery system (SNEDDS) has shown great improvement in the enhancement of drug bioavailability. The selection of appropriate compositions in the SNEDDS formulation is the fundamental step towards developing a successful formulation. This study sought to evaluate the effectiveness of fractional factorial design (FFD) in the selection and screening of a SNEDDS composition. Furthermore, the most efficient FFD approach would be applied to the selection of SNEDDS components. Methods: The types of oil, surfactant, co-surfactant, and their concentrations were selected as factors. 2(6) full factorial design (FD) (64 runs), 2(6-1) FFD (32 runs), 2(6-2) FFD (16 runs), and 2(6-3) FFD (8 runs) were compared to the main effect contributions of each design. Ca-pitavastatin (Ca-PVT) was used as a drug model. Screening parameters, such as transmittance, emulsification time, and drug load, were selected as responses followed by particle size along with zeta potential for optimized formulation. Results: The results indicated that the patterns of 2(6) full FD and 2(6-1) for both main effects and interactions were similar. 2(6-3) FFD lacked adequate precision when used for screening owing to the limitation of design points. In addition, capryol, Tween 80, and transcutol P were selected to be developed in a SNEDDS formulation with a particle size of 69.7± 5.3 nm along with a zeta potential of 33.4± 2.1 mV. Conclusion: Herein, 2(6-2) FFD was chosen as the most efficient and adequate design for the selection and screening of SNEDDS composition. The optimized formulation fulfilled the requirement of a quality target profile of a nanoemulsion.