Quality-by-design development of Celtis iguanaea microparticles with In vivo gastroprotective efficacy

Abstract

A spray-dried hydroethanolic leaf extract of Celtis iguanaea (Jacq.) Sarg., Cannabaceae, was developed and evaluated for its gastroprotective efficacy in mice. A 33 Box-Behnken design (n = 15) and Response Surface Methodology were used to optimize the spray drying. The variables studied were drying air inlet temperature (100 – 140 °C), extract feed flow rate (0.3 – 0.7 l/h), and leucine content (15 – 45% m/m relative to solids) as a drying aid. The inlet temperature and leucine content were the main factors affecting the drying process. Optimal conditions were an air inlet of 120 °C, an extract feed flow rate of 0.3 l/h, and a leucine content of 45%, achieving a yield of 52% with microparticles of 3.4 µm. However, energy efficiency requires improvements. The optimized spray-dried hydroethanolic leaf extract of C. iguanaea contained 21.8 mg/g total polyphenols, 49.7 mg/g flavonoids, and 518.8 mg/g phytosterols, with an IC50 of 301.6 µg/ml and an electrochemical index of 6.1 µA/V. LC-UV, ESI(-)-MS, and LC-PDA analyses identified hydroxycinnamic acid and two flavones as major compounds. Regardless of the use of leucine as a drying aid, spray drying proved more effective than freeze drying in preserving bioactive compounds. In an indomethacin-induced gastric ulcer model, spray-dried hydroethanolic leaf extract of C. iguanaea (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 Quality by Design 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.