QbD-Guided Formulation and Optimization of Lyophilized Dry Emulsion of Nicardipine Hydrochloride Employing Caprylic Capric, Tween 80, and Transcutol® HP Using Box–Behnken Design

Purpose The study developed and optimized a lyophilized dry emulsion (LDE) of nicardipine hydrochloride (NHCl) using a pseudo-ternary phase diagram (PTPD) and a Box–Behnken design (BBD) to enhance aqueous solubility and to obtain a free-flowing, compressible powder suited for solid dosage form development. Methods A PTPD was constructed using caprylic capric (CC), Smix (Tween 80 and Transcutol® HP, 1:1), and a water phase (WP) containing maltodextrin and sodium alginate to define the emulsifying region. A BBD with CC, Smix, WP, temperature, and vacuum as independent variables was used to generate formulations. The solubility responses of these formulations were analyzed by Analysis of Variance (ANOVA) and response surface methodology (RSM) to identify an optimized batch. The optimized LDE (OLDE) was prepared under the predicted conditions and evaluated for zeta potential, solubility, flow properties, X-ray diffraction (XRD), and Scanning Electron Microscope (SEM). Results The PTPD identified an emulsification region, and BBD analysis revealed Smix, CC, and WP as key factors influencing solubility. The OLDE exhibited a solubility of 1.698 ± 0.010 mg/mL, higher than the pure NHCl. It showed good flow properties-Angle of repose 29.85°, Hausner ratio (HR) 1.15, Carr’s index (CI) 13.09% and a zeta potential of − 26.2 mV, indicating emulsion stability. XRD and SEM analyses confirmed reduced crystallinity and formation of amorphous matrix. Conclusion A PTPD-guided and BBD-OLDE successfully enhanced the aqueous solubility and flow properties of NHCl. The OLDE of NHCl exhibited good physicochemical and solid-state characteristics, supporting promising platform for the NHCl solid oral dosage forms.