Quality-by-Design development of Celtis iguanaea (Jacq.) Planch (Cannabaceae) microparticles with in vivo gastroprotective efficacy

Celtis iguanaea , widely used in Brazilian folk medicine, is known for its gastroprotective properties. This study aimed to develop a spray-dried hydroethanolic leaf extract of C. iguanaea (SDCi) and evaluate its gastroprotective efficacy in mice. A Box-Behnken design with three factors at three levels (n = 15) and Response Surface Methodology (RSM) were used to optimize the spray drying. The variables studied were drying air inlet temperature (IT, 100–140°C), extract feed flow rate (Ef, 0.3–0.7 L/h), and leucine content (Lc, 15–45% m/m relative to solids) as a drying adjuvant. The IT and Lc were the main factors affecting the drying process. Optimal conditions were IT of 120°C, Ef of 0.3 L/h, and Lc of 45%, achieving a yield of 52.0% with microparticles of 3.4 µm. However, energy efficiency requires improvements. The optimized SDCi contained 21.8 mg/g total polyphenols, 49.7 mg/g flavonoids, and 518.8 mg/g phytosterols, with IC ₅₀ of 301.6 µg/mL and electrochemical index of 6.1 µA/V. LC-PDA, LC-UV, and ESI(-)-MS analyses identified hydroxycinnamic acid and two flavones as major compounds. In an indomethacin-induced gastric ulcer model, SDCi (150 and 300 mg/kg, p.o.) significantly reduced the lesion index, potentially due to its immunomodulatory effects, including decreased IL-1β and increased IL-10 levels in the stomach. This QbD approach successfully developed a high-value phytopharmaceutical intermediate product with favorable yield, antioxidant properties, and in vivo gastroprotective efficacy. Further studies on stability, pharmacokinetics, drug interactions, and human safety are needed to support its use in Brazilian complementary medicine.